Displaying One Session

On-Demand e-Poster Display Poster Display
Date
20.11.2020
Time
09:00 - 20:00
Location
On-Demand e-Poster Display
e-Poster Display Session (ID 87) Poster Display

Breast cancer, early stage (ID 1141)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

7P - Machine learning intratumoral and axillary lymph node magnetic resonance imaging radiomics for predicting axillary lymph node metastasis in patients with early-stage invasive breast cancer (RBC-01 Study) (ID 991)

Presentation Number
7P
Lecture Time
09:00 - 09:00
Speakers
  • Yujie Tan (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In current clinical practice, the routine approaches of axillary lymph node (ALN) status evaluation through sentinel lymph node biopsy (SLNB) is unsatisfied with high false-negative rate and brings significant complications. We aimed to develop a preoperative magnetic resonance imaging radiomic-based signature for predicting ALN metastasis (ALNM) in a non-invasive way.

Methods

A total of 1,090 early-stage invasive breast cancer patients from 4 institutions were enrolled in this multicenter, retrospective, diagnositc study. Radiomic signature for ALNM prediction were constructed by machine learning in 803 patients from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (Training cohort). The clinical-radiomic siganture was constructed by combining radiomic signature and significant clinic-pathological risk factors and was validated in patients from prospective phase III trials [NCT01503905] (Internal validation cohort, n=106), and Shunde Hospital and Tungwah Hospital (External validation cohort, n=181). This study is registered with ClinicalTrials.gov (NCT04003558) and Chinese Clinical Trail Registry (ChiCTR1900024020).

Results

The radiomic signature for predicting ALNM consisted of intratumoral and ALN features showed AUCs of 0.91, 0.88, and 0.85 in the training, internal validation and external validation cohorts. The clinical-radiomic signature achieved the highest AUCs of 0.93, 0.91, and 0.91 in the training, internal validation and external validation cohorts, which successfully discriminate high- from low risk relapse patients (HR 0.12, 95% CI 0.03–0.53; P<0.001) and was similar to the performance in ALNM and non-ALNM (HR 0.28, 95% CI 0.09–0.87; P=0.002). In additon, the clinical-radiomic signature also performed well in the subgroup of N1, N2, N3 status (AUCs of 0.89, 0.90, 0.97).

Conclusions

This study developed a clinical-radiomic signature incorporated the intratumoral and ALN radiomic features and clinical risk factors, which could serve as a non-invasive tool to evaluate ALN status for guiding surgery plans of early-stage breast cancer patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

8P - Knowledge, practice and attitudes of physicians in low- and middle-income countries (LMIC) on fertility and pregnancy-related issues in young breast cancer patients (ID 781)

Presentation Number
8P
Lecture Time
09:00 - 09:00
Speakers
  • Shah Zeb Khan (Bannu, Pakistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Fertility and pregnancy-related issues are a priority area of concern for young breast cancer (BC) patients (pts). Limited evidence exists on knowledge, practice and attitudes of physicians practicingin low- and middle-income countries (LMIC)towards these issues.

Methods

A 19-item questionnaire adapted from an international survey (Lambertini et al, Breast 2018) exploring issuesaboutfertility preservation and pregnancy after BCwas sent by email to physicians from LMIC involved in BC care.Descriptive analyses were performed.

Results

A total of 288 physicians completed the survey. Median age was 38 years (interquartile range 33-45).Respondents from Asia, Africa, America and Europe filled in the survey: the 3 most represented countries were Mexico (27.1%), India (18.4%) and Brazil (8.3%).The majority of respondents were medical oncologists (44.4%)working in an academic setting (46.9%). Among respondents, 40.2% and 53.8% reported never having consulted the available international guidelines on fertility preservation and pregnancy after BC, respectively. 25.0%, 19.1% and 24.3% of respondents declared to be not at all knowledgeable about embryo, oocyte or ovarian tissue cryopreservation, respectively. 29.2%, 23.6% and 31.3% declared that embryo, oocyte and ovarian tissue cryopreservation are not available in their countries, respectively. 57.6% of respondents disagreed or were neutral on the statement that controlled ovarian stimulation (COS) can be considered safe in BC pts; 29.9%suggested that COS should not be considered safe in pts with hormone receptor-positive (HR+) disease. 49.7% and 58.6% of respondents agreed or were neutral on the statement that pregnancy in BC survivors may increase the risk of recurrence overall or only in those with HR+ disease, respectively. In contrast, 49.0% agreed that COS in BC survivors can be safely considered.

Conclusions

Several misconceptions exist among physicians from LMIC on fertility and pregnancy-related issues in young BC pts. Increased awareness and further educational initiatives are needed to improve adherence to available guidelines and pts’oncofertility counseling.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.F. Ponde: Advisory/Consultancy: Lilly; Honoraria (self): Roche,Novartis, AstraZeneca and Lilly. M. Brandão: Honoraria (self), Travel/Accommodation/Expenses: Roche/GNE. I.B. Spasojevic: Advisory/Consultancy: Roche, Novartis, Amicus; Honoraria (self): Roche, Novartis, Pfizer, AstraZeneca. A. Odhiambo: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Roche, Novartis; Advisory/Consultancy: Pfizer, AstraZeneca, Janssen. M. Tagliamento: Travel/Accommodation/Expenses: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; Full/Part-time employment, Medical Writer: Novartis, Amgen. M. Lambertini: Advisory/Consultancy: Roche, Novartis; Honoraria (self): Roche, Takeda, Theramex, Novartis, Pfizer, Lilly. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

9P - Survival status of elderly women with HR+ early breast cancer: An analysis of SEER database (ID 430)

Presentation Number
9P
Lecture Time
09:00 - 09:00
Speakers
  • Wang Hao (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Women with HR+(ER and/or PR positive) in early breast cancer usually have a better outcome than other cancer variants. However, as the patient age, there were few reports on the survival status of elderly women in HR+ early breast cancer and concomitant diseases. Base on a large-scale population, the results of statistical analysis would aid in clinical decisions and effective interventions on the treatment of elderly patients.

Methods

Based on the Surveillance, Epidemiology, and End Results (SEER) database, elderly (age≥60) female patients diagnosed HR+ early breast cancer from 2010 to 2016 were included. They were divided into two groups: elderly patients (age 60-74, group A) and senior elderly patients (age≥75, group B). Kaplan-Meier survival analysis was used to compare the 5-year overall survival (OS) rate, cumulative mortality, and the proportion cause of death.

Results

In total there were 147,969 cases were included, which were 100,091 cases in group A and 47,878 cases in group B. The 5-year OS in group A and B were 89.9% vs. 68.8% (HR 3.53, 95% CI 3.43-3.64, P < 0.001) respectively. The proportion of HER2- and HER2+ cases in group A were 90.2% and 9.8%, which 5-year OS were 90.2% vs. 87.7% (HR 0.77, 95% CI 0.72-0.83, P < 0.001). The proportion of HER2- and HER2+ cases in group B were 91.9% and 8.1%, which 5-year OS were 69.5% vs. 61.0% (HR 0.70, 95%CI 0.66-0.75, P < 0.001). There was no significant difference in cumulative mortality between breast and non-breast cancer related deaths (HR: 0.98, 95% CI 0.93-1.03, P = 0.4) in group A; but that was significantly difference in group B (HR: 0.77, 95% CI 0.733-0.799, P < 0.001). The primary non-breast related death in group A were diseases of the heart (12.1%), COPD and related conditions (4.8%); while in group B that were diseases of the heart (20.43%) and cerebrovascular disease (5.4%).

Conclusions

The risk of death in elderly HR+ early breast cancer patients was relatively increasing with age, especially the death caused by cardiovascular and cerebrovascular events. HR+/HER2+ patients have a higher risk of death requiring further intensive treatment. The age-related comorbidity risk and breast cancer subtypes should be considered in the treatment of these patients to make a comprehensive treatment decision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

10P - Neoadjuvant immunotherapy plus chemotherapy in early triple-negative breast cancer: A meta-analysis of randomized controlled trials (ID 531)

Presentation Number
10P
Lecture Time
09:00 - 09:00
Speakers
  • Jessa Gilda P. Pandy (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the early stages, the use of neo-adjuvant systemic treatment is the standard of care in TNBCs. Patients who achieve a pathological complete response (pCR) have improved survival outcomes. The programmed cell death receptor ligand, PD-L1, has been shown to have high expression in TNBCs. To date, major research efforts are being undertaken to determine the applicability of PD-1/PD-L1 immune checkpoint inhibitors in TNBC.

Methods

A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify RCTs investigating the use of neoadjuvant PD-1/PD-L1 inhibitors plus standard chemotherapy in TNBC. Trials that were published up to March 2020 were included and were appraised. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) were calculated for pCR. Subgroup analysis of pCR rates based on PD-L1 expression was also done.

Results

Four RCTs were included (N=384). The addition of immunotherapy to chemotherapy in the neo-adjuvant setting showed significant pCR benefit of 58.5% vs 42.2% compared to chemotherapy alone (OR 1.76, 95% CI 1.11-2.79, P <0.02). Subgroup analysis based on PD-L1 expression showed that in the immunotherapy plus chemotherapy group, there is a significantly higher pCR rate in the PD-L1-positive population than in the PD-L1 negative group (64.5% vs 39.4%). The addition of immunotherapy showed a significant benefit in improving pCR in the PD-L1-positive group (OR 1.55, 95%CI 1.16-2.09, p = 0.003, I2 =0%).

Conclusions

The addition of PD-1/PD-L1 inhibitors to standard chemotherapy is associated with increased pCR rates in patients with TNBC, hence, supporting its use for patients in the neo-adjuvant setting. Subgroup analysis showed that the benefit of adding immunotherapy was more significant in those with PD-L1-expressing tumors. This result indicates that the PD-L1 immune marker may have utility in selecting TNBC patients who can benefit more from PD-L1 inhibitors. Longer follow-up and further analysis of these studies would hopefully demonstrate significance in other outcomes such as progression-free survival and overall survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

11P - Genetically predicted bipolar disorder is causally associated with increased risk of breast cancer: A Mendelian randomization analysis (ID 683)

Presentation Number
11P
Lecture Time
09:00 - 09:00
Speakers
  • Haoxin Peng (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Epidemiologic findings suggested that bipolar disorder (BD) may be associated with increased risk of breast cancer. However, there are few studies that comprehensively evaluate their correlation and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods

Utilizing 6 BD-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122 977 cases and 105 974 controls. Study-specific estimates were summarized using inverse-variance-weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical type of breast cancer were also conducted.

Results

MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR = 1.058; 95% CI 1.023-1.093, p < 0.001). When results were examined by immunohistochemical type, a strong association was observed between genetically predicted BD and estrogen receptor-positive (ER) breast cancer (OR = 1.048, 95%CI 1.008-1.090 p = 0.0177) rather than ER-negative breast cancer (OR = 1.026, 95%CI 0.975-1.081 p = 0.3231). Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Mendelian randomization estimates of the associations between bipolar disorder and risk of breast cancer overall and immunohistochemical types

Outcome IVW method MR-Egger Weighted median method
OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value
Breast cancer overall 1.058 (1.023, 1.093) 0.0009 1.032 (0.969, 1.099) 0.3858 1.044 (1.006, 1.083) 0.0239
ER-positive breast cancer 1.048 (1.008, 1.090) 0.0177 1.004 (0.942, 1.070) 0.9118 1.030 (0.998, 1.074) 0.1622
ER-negative breast cancer 1.026 (0.975, 1.081) 0.3231 1.085 (0.986, 1.195) 0.1713 1.041 (0.978, 1.109) 0.2063

Conclusions

Our findings provide evidence for a causal relationship between genetically predicted BD and increased breast cancer risk, overall and among specific immunohistochemical type. Further studies are warranted to investigate the underlying mechanism.

Legal entity responsible for the study

Haoxin Peng.

Funding

China National Science Foundation (Grant No. 81871893); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); Cultivation of Guangdong College Students' Scientific and Technological Innovation (“Climbing Program” Special Funds) (Grant No. pdjh2020a0480).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

12P - Stromal tumour-infiltrating lymphocytes in human epidermal growth factor receptor 2-overexpressing breast cancer: Association with negative nodal metastasis (ID 804)

Presentation Number
12P
Lecture Time
09:00 - 09:00
Speakers
  • Ren Xiaoqiu (Hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The tumor-infiltrating lymphocytes (TILs), especially stromal TILs, have showed a prognostic role in human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer. Stromal TILs are associated with higher pathological complete remission (pCR) rates after neoadjuvant chemotherapy. However, the relation between stromal TILs in primary breast cancer and axillary nodal metastasis remains uncertain.

Methods

A retrospective review of pathological reports of 763 patients with breast infiltrating ductal carcinoma (IDC) was conducted. The gene expression and clinical data of 662 IDC cases were downloaded from the TCGA database. In silico analysis was based on the gene expression data. The “Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data” (ESTIMATE) algorithm was used to calculate the stromal and immune scores in N0 and N+ cases.

Results

In HER2+ breast cancer, the fractions of stromal TILs are higher than 30% (37.57% versus 19.67%, P=0.01) and 40% (25.97% vs 8.20%, P=0.003) in lymph node negative cases comparing to nodal metastasis cases. The fractions of stromal TILs in HER2- breast cancer showed no difference between N0 and N+ stage cases. We further compare the fractions of stromal TILs between N0 and N+ cases in different subtypes of breast cancer cases. The stromal TILs (%) is only higher in primary tumors of N0 HER2 amplified breast cancer cases than N+ cases (P=0.014). The stromal TILs (%) of primary tumors are similar between N0 and N+ cases in Luminal A (hormone receptor (HR)+/HER2-) (P=0.261), Luminal B (HR+/HER2+) (P=0.838) and triple negative (HR-/HER2-) subtypes (P=0.456). The primary tumors immune scores of N0 and N+ cases show no significantly difference in HER2+/- breast cancer. The stromal scores of N+ cases are higher than N0 cases in HER2+ breast cancer (P=0.015). The stromal scores are similar between N0 and N+ cases in HER2- breast cancer.

Stromal TILs(%) N0(cases) % N+(cases) % P value
Her2+ 0-9 72 39.78 28 45.90
10- 109 60.22 33 54.10
0.401
0-19 101 55.80 40 65.57
20- 80 44.75 21 34.43
0.181
0-29 113 62.43 49 80.33
30- 68 37.57 12 19.67
0.01
0-39 134 74.03 56 91.8
40- 47 25.97 5 8.2
0.003
Stromal TILs(%) N0(cases) % N+(cases) % P value
Her2+ 0-9 219 59.03 83 55.70
10- 152 40.97 66 44.30
0.487
0-19 286 77.09 115 77.18
20- 85 22.91 34 22.82
0.982
0-29 313 84.37 124 83.22
30- 58 15.63 25 16.78
0.747
0-39 335 90.30 135 90.60
40- 36 9.70 14 9.4
0.914

Conclusions

The higher fraction of stromal TILs is negatively related to lymph nodes metastasis in her2-positive breast cancer. Since the stromal fraction of tumor tissue may be higher in HER2+ N+ breast cancer, it also tends to be associated with nodal metastasis. In total, it is not the absolute quantity of immune cells, but the relative quantity of TILs in tumor stroma (which we evaluated as stromal TILs (%)) makes a vital role in predicting nodal stage of HER2 amplified IDC.

Legal entity responsible for the study

Weiqichun.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

13P - A retrospective observational study on neoadjuvant chemotherapy in older adults based on the Joint Breast Cancer Registry Singapore (ID 627)

Presentation Number
13P
Lecture Time
09:00 - 09:00
Speakers
  • Johan Chan (Singapore, SA, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

According to the SEER cancer statistics from 2013 to 2017, 43.4% of all newly breast cancers are diagnosed in women aged 65 years and older. Despite a relatively high prevalence of older adults with newly diagnosed breast cancer, elderly patients are often under-represented in the pivotal neoadjuvant trials. Recommendations for treatment with neoadjuvant chemotherapy (NAC) are based on subgroup analyses and extrapolation of study results from younger patients.

Methods

This retrospective observational study collected data from the Joint Breast Cancer Registry (JBCR) on older adults aged ≥ 65 years treated with NAC for breast cancer at the National Cancer Centre Singapore from October 2014 to October 2019. Patients in the JBCR had detailed clinical and pathological information including hormone receptor (HR), HER2 status, type of NAC. Outcomes and adverse events were retrieved from electronic medical records. Pathological complete response(pCR) was defined by the absence of residual disease in the breast and lymph nodes following NAC.

Results

Of 353 patients who underwent NAC, 66(18%) patients were older adults aged ≥ 65 years. Patients characteristics are decribed in the table. The median age was 69 (65-83) years. 31(46%) patients had HER2+ disease. 13(19%) were triple negative breast cancer (TNBC). 18(27%) patients were unable to complete NAC, of which 10(15%) were due to side effects while 5 (7.5%) had progressive disease during treatment and the remainder 3(5%) refused the planned treatment. Half of the cohort with HER2+ disease had anthracycline/taxane based chemotherapy along with HER2 directed therapy of either trastuzumab or the combination trastuzumab and pertuzumab. 13 (19%) patients had pCR, 11 were HER2+ while 1 was HR+/HER 2- and the other was TNBC.

Patient characteristics

No. (%)
Breast cancer diagnosis that are 65 years and above 66 (18)
median age (Range) 69 (65-83)
median ECOG(range) 0 (0-2)
Clinical T Staging
2 14 (21)
3 to 4 52 (79)
Clinical N Staging
0 14 (20)
1 to 3 51 (79)
nX 1
HR status
Negative 25(37)
Positive 41(63)
Human epidermal growth factor receptor 2 (HER2)
Negative 35 (54)
Positive 31 (46)
Histology
HR+ /HER2- 22 (33)
HR +/ HER2+ 19 (28)
HR - / HER2+ 12 (18)
Triple negativeTNBC (HR- /& HER2-) 13 (18)
NACcompleted/ NAC not completed 48(72) / 18 (27)
IncompletionReason
PD 5(27)
Side effects 10(55)
Refused treatment 3 (16)
Pathological Complete Response
Overall 13(18)
TNBC 1
Her2+ 11(17)
ER +/ HER2- 1

Conclusions

We report a cohort of older adults who had undergone NAC at our centre. Consistent with existing studies, 72 % of the patients completed NAC. In keeping with data on younger patients, older adults with HER2+ breast cancer had higher pCR. However, unlike younger women with TNBC, older adults in this study had lower rates of pCR which was also noted in a recent pooled analysis. This could reflect a heterogeneity of TNBC in older women which warrants further investigations in the future

Legal entity responsible for the study

CIRB Singhealth 2019/093/A.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

14P - BRCA mutation and clinical outcomes in breast cancer focusing on survivals and failure patterns: A long-term follow-up study of Koreans (ID 353)

Presentation Number
14P
Lecture Time
09:00 - 09:00
Speakers
  • Hakyoung Kim (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The purpose of this study was to evaluate the effect of BRCA mutation on survival and recurrence rate, focusing on risk of ipsilateral recurrence and contralateral breast cancer in breast cancer patients who underwent genetic screening for BRCA1/2 mutation and were treated at Samsung Medical Center.

Methods

We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between January 1, 2000 and December 31, 2010. Ultimately, clinical outcomes of 273 patients were analyzed.

Results

The median follow-up duration was 102 months (range, 1 to 220 months). BRCA1/2-mutated tumors had shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, BRCA1/2-mutated tumors showed higher incidence of contralateral breast cancer than non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155, 95% CI: 1.789-9.652; p = 0.001).

Conclusions

Korean patients having BRCA mutation showed inferior DFS compared to those without BRCA mutation. BRCA mutation status is a strong predictor of recurrence in contralateral breast. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have BRCA mutations.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

15P - Designing of multimodal targeted tumor-seeking nanomedicine for triple-therapeutic effect (ID 156)

Presentation Number
15P
Lecture Time
09:00 - 09:00
Speakers
  • Vellingiri Yasothamani (Coimbatore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is a major ongoing health problem among women in both developing and developed countries. Her2/neu positive is the subtype of breast cancer. We tested an integrated innovatively designed new tumour-seeking nanomedicine (TSN) for high therapeutics antitumor effect on advanced breast cancer that overexpressed the Her2/neu receptor.

Methods

Herein, we designed the special photodynamic molecule porphyrin combined with the anticancer drug doxorubicin (DOX), enabling it to target cancer biomarkers and measuring the singlet oxygen production with thermal heat to archive extraordinary selective PDT/PTT/Chemotherapy in vitro. The tumor-seeking nanomedicine (TSN) targets the triple therapeutic effect of breast cancer. Furthermore, in vivo phototherapy and chemotherapy using targeted nanoparticles in mice models were also done.

Results

Encouragingly, multimodal targeted TSN shows selective Her2/neu receptor-mediated response in breast cancer, incinerates the tumor treated under NIR irradiation triggering the porphyrin and DOX co-release and enhancing the distribution of DOX in nuclei; the released porphyrin molecules also function as multiphase that can efficiently convert NIR-light to heat inside tumor cells for PTT, and again NIR-light to singlet oxygen for PDT. Due to these unique properties, TSN had excellent antitumor effects under NIR irradiation. The excellent role of TSN based triple-targeted therapy produced the best anticancer response to trigger the tumor cell death and was effective to protect the mice from cancer relapse.

Conclusions

Conjugation of porphyrin and DOX for the evaluation of such complexes in phototherapy in Her2/neu target human cancer cells. This multi-model therapy approach will make it much more effective to overcome tumors than a single therapeutic approach. TSN exhibited high selectivity and efficient tumor inhibition in-vivo without affecting the normal tissues. Therefore the clinical translation of our TSN and the proposed way might be realistic and the integrated components of TSN have been approved by the US FDA for human clinical usage. Therefore, integrated TSN achieved unprecedented selectivity and shows highly versatile next-generation clinical translation for advanced nanomedicine against cancers.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

16P - Topical henna cream in prevention of radiation-induced dermatitis in breast cancer: A randomized double-blind clinical trial (ID 983)

Presentation Number
16P
Lecture Time
09:00 - 09:00
Speakers
  • Mansour Lesan (Tehran, Iran)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Radiotherapy plays an important role in the treatment of cases who had breast conserving surgery. Breast cancer patients who receive radiotherapy develop acute skin complications which are known as radiation dermatitis (RD) during radiotherapy or shortly after it. Radiation dermatitis is one of the most common side effects. It affects approximately 95% of patients. This complication has a profound effect on patients' quality of life due to pain and discomfort and can reduce tolerance to treatment and in some cases discontinuation or delay of radiotherapy. This can effect disease control in the long term. So, prevention and treatment of RD is important for health care providers and it is essential to produce effective health products to prevent and treat this disease. Henna (Lawsonia inermis L.) is a medicinal plant which has antimicrobial, anti-inflammatory, and skin-enhancing properties, all of which are useful for people who have radition dermatitis. Also, studies have shown antimicrobial, anti-inflammatory, analgesic, and wound healing effects of henna. This research aimed to evaluate the efficacy of a topical henna preparation (HP) in preventing and reducing the severity of RD in breast cancer patients.

Methods

This was a prospective double-blind clinical study which contained 43 breast cancer patients aged 18-75 years who had breast-conserving surgery and were going to receive radiotherapy. They were randomly allocated into two groups, those who received the topical HP or those who received placebo, twice daily for six weeks, from the first day of treatment. Grade of dermatitis was evaluated weekly based on RTOG grading system.

Results

The present study showed that HP could reduce the severity of RD. The use of HP delayed the onset of grade 2 RD for two weeks, also, it delayed the onset of grade 3 RD for one week compared to the placebo group. At the end of the sixth week, in the patients who received the HP, the grade 2 RD (20% vs. 56.52%) as well as grade 3 RD (10% vs. 26.09%) significantly decreased (p=0.004).

Conclusions

Topical henna cream is an inexpensive and accessible herbal medicine that can be effective in preventing and reducing the severity of RD in patients with breast cancer.

Clinical trial identification

IRCT2019110704537N1.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

17P - Comparison of dose distribution in the postoperative breast cancer patients irradiated with the technique of deep inspiratory breath hold and dynamic techniques (ID 148)

Presentation Number
17P
Lecture Time
09:00 - 09:00
Speakers
  • Ewa B. Telka (Gliwice, Poland)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is the most common cancer in women in Poland. In patients with cancer located on the left side, breast radiotherapy is associated with the irradiation of part of the heart. It was calculated that for every 1 Gy dose of radiation deposited in the heart, the risk of heart complications increases by 7.4%.

Methods

The subject of analysis was a group of 50 patients treated in the National Institute of Oncology, Department of Radiotherapy, Gliwice from June 2018 to December 2019. The age of patients ranged from 30 to 70 (median 63 years). All patients were after surgeries (38 patients after BCT with SNB and 12 patients after left breast amputation). All patients were additionally irradiated using Deep Inspiratory Breath Hold technique. Dose distributions per heart and lungs were compared in IMRT, Rapid Arc, and DIBH techniques. Radiation complications from the skin were assessed according to WHO scale.

Results

In all irradiated patients the dose distribution in the technique on suspended inhalation was better compared to the dynamic IMRT and Rapid Arc techniques, with dose reduction per heart by about 10-15% and per lung from 5 to 10%. No higher than II degree of acute and late skin reaction in the DIBH technique was observed in comparison with dynamic techniques.

Conclusions

1) Deep Inspiratory Breath Hold technique is a simple non-invasive method which effectively reduces the dose of radiation absorbed by the heart muscle. 2) Irradiation of patients with deep inspiratory allows a reduction of the lungs dose by about 5-10 %. 3) The technique of irradiation of patients during deep inspiratory is a simple, non-invasive method of treatment of patients reducing the risk of radiation complications from the heart and the lungs in comparison with dynamic, IMRT, and Rapid Arc techniques.

Legal entity responsible for the study

The authors” without further recourse to the authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

18P - A prospective randomized study comparing cosmetic outcome of sequential electron boost versus simultaneous integrated boost with IMRT to lumpectomy cavity during adjuvant radiotherapy to breast following BCS in carcinoma breast in Indian patients (ID 595)

Presentation Number
18P
Lecture Time
09:00 - 09:00
Speakers
  • Sravya Bommera (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Compared to sequential conventional fractionation schedule, Simultaneous integrated Boost provides increased dose homogeneity, with less unintended excessive dose outside the boost area; in combination with a higher dose per fraction to the tumour bed, resulting in a shorter overall treatment time spanning over 5 1⁄2 weeks. We compared cosmesis using the Harvard cosmesis scale and dosimetry of SIB IMRT versus sequential electron boost in breast cancer patients.

Methods

Patients in our Institute who have undergone breast-conserving surgery and received adjuvant chemotherapy, who are referred for adjuvant radiotherapy. The study period spanned from 1st May 2016 to 31st March 2018.

Results

The baseline Harvard score for grading breast cosmesis in both the arms was excellent (84% in SIB and 81% in SEB) or good(16% in SIB and 19% in SEB). None of the patients in either arm had fair or poor cosmesis. Assessment of cosmesis at the end of radiation therapy showed a dip from excellent to good and fair in both the arms ( 34% versus 9% with excellent cosmesis, 53% versus 72% with good cosmesis and 13% versus 19% with poor cosmesis in SIB versus SEB arms) but the patients in the SEB arm had comparatively much lower cosmetic score. However, this difference was not statistically significant(p=0.045). Overall cosmesis at the end of 3 months was better in SIB arm compared to that of the SEB arm and was statistically significant (93% with excellent and good cosmesis in SIB vs 65% in SEB p<0.001). At 6 months of follow-up in SIB arm, there was an improvement of the cosmesis with a majority of the patients showing excellent(59%) and good (34%) cosmetic score.

Conclusions

In a selected cohort of patients who have undergone breast conservation surgery, a simultaneous integrated boost along with WBI is considered equivalent radiobiological to sequential electron boost after WBI. This study reports better cosmetic outcomes and favourable toxicity profile with SIB compared to SEB over short-term follow-up which is statistically significant.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

19P - Musculoskeletal pain and health-related quality of life among breast cancer patients (ID 234)

Presentation Number
19P
Lecture Time
09:00 - 09:00
Speakers
  • Aslin S. Valiyagath (Thrissur, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The musculoskeletal pain is one of the leading health problems among women. This study aims to examine the associations between musculoskeletal pain and health-related quality of life (HR-QOL) among breast cancer patients and women without a history of breast cancer.

Methods

A cross-sectional study was conducted among 68 breast cancer patients for an average of 3.5 years and 137 postmenopausal women without a history of cancer. Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was examined using the Medical Outcomes Study Short Form (SF-36) health survey. Linear regression was used to estimate the associations between pain and HR-QOL in both groups.

Results

Approximately 64 % of the breast cancer patients andwomen in the comparison group reported musculoskeletal pain.Among women with breast cancer, those with pain had significantlylower HR-QOL scores in the physical (52.2 vs. 42.6;p<0.001) and mental (52.7 vs. 45.5; p=0.01) component summary scores compared with those without pain. In the comparisongroup, pain was associated with significantly lower scores in the physical (55.4 vs. 46.0; p<0.001), but not the mental, component summary score (52.1 vs. 52.4; p=0.82). The significantassociations between pain and HR-QOL persisted afterconfounder adjustment in both groups. Among women withsimilar severity of pain, breast cancer patients reported significantlylower HR-QOL in the mental summary component compared with the women in the comparison group.

Conclusions

Among breast cancer patients, musculoskeletal pain adversely affects both mental and physical components of HR-QOL. Preventing or treating musculoskeletal pain may improve overall HR-QOL among breast cancer patients.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

20P - Molecular parallelisms and divergences between human and canine cancers (ID 347)

Presentation Number
20P
Lecture Time
09:00 - 09:00
Speakers
  • Sadaf Ambreen (, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumorigenesis has been widely accepted as an evolutionary process that comprises two stages of evolution between tumors and normal tissues (Stage I) and within tumors (Stage II) 1. Patterns of mutation and natural selection, the predominant evolutionary driver forces, vary at the two stages based on the evidence of low genetic convergence among different cancer cases revealed by The Cancer Genome Atlas (TCGA) data and of extremely high intra-tumor genetic diversity measured in high-density sampling studies (Ling et al. 2015; Sottoriva et al. 2015). At Stage, I, positive and negative selection may both exist but neatly counteract in absence of recombination, presenting a plausible neutrality 1, whereas non-Darwinian (neutral) selection was increasingly supported at Stage II by the high-density sampling studies and comparatively genomic and transcriptional distances among distinct normal and cancerous cell populations. Deciphering the evolutionary patterns during tumorigenesis such as selectivity or neutrality, adaptive convergence, or divergence is of both theoretical and clinical significance. Cross-species cancer genomics, independent evolution from normal tissues, provide an excellent opportunity to address this long-standing issue: Does selection drive cancer evolution along with a relatively deterministic (selectivity) or contingent (neutrality) way across species?

Methods

GATAK pipeline and Mutect2.

Results

We performed whole-genome sequencing analysis by using GATAK pipeline and Mutect2 for twenty-four dog mammary cancers and identified 47715 somatic mutations comprising 210 exonic mutations. Comparison between human and dog reveals similarities and differences in the mutation profiles across both species, in terms of the mutated driver genes and mutation number, which are likely to influence tumor behavior and response to treatments. Human breast cancer had a higher median mutation burden comparable to canine mammary cancer, in exonic regions (2.67 and 0.187 average no. of mutations per tumor per megabase (Mb), respectively).

Conclusions

Taken together, for the first time, we reported canine mammary tumors comprising mutated genes, mutation burden, mutational patterns, spectrums, and signatures at the whole genome level.

Legal entity responsible for the study

The author.

Funding

CAS-TWAS.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

21P - Neoadjuvant trastuzumab and pertuzumab in real-world data population in two medical institutions in Portugal (ID 988)

Presentation Number
21P
Lecture Time
09:00 - 09:00
Speakers
  • Isabel C. Gomes Fernandes (Barreiro, Portugal)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neoadjuvant treatment (NAT) refers to the treatment that is administered before surgery for the treatment of cancer. For the last few years the medical community noticed that achieving complete pathological response (pCR), for HER2+ breast cancer patients, after the NAT equates to a long-term surrogate point, which has pushed for the development of treatment strategies based of neoadjuvant use of trastuzumab and pertuzumab. We implemented an institutional protocol in 2018 to treat HER2+ breast cancer patients that had tumours larger than 2cm and/or axillary disease that had had included anthracyclins, taxanes, trastuzumab and pertuzumab on their NAT regimen. The main goal was to prospectively analyse the effect of this neoadjuvant regimen on pCR (ypT0/is, ypN0/is), as well as on how often does NAT help with breast conservation.

Methods

This non-randomized prospective study was performed in two medical oncology departments in Portugal. It included HER2+ breast cancer patients that had tumours larger than 2cm and/or axillary disease that have been being treated since 2018. These patients were put on the following treatment scheme: 4 cycles of doxorrubicin and cyclofosfamid, followed by 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles.

Results

A total of 38 patients were included in the study. The median age: 54 years; 17 patients had stage II cancer and 21 patients stage III. 26 patients had a ki67 >20%. pCR was achieved in 60,5% of the patients, 58,6 % in the hormonal receptor (HR) positive subgroup and 66,7% in HR-negative patients. 57,9% of the patients received breast conservative surgery and 65,9% received axillary dissection. Only one patient didn’t complete the protocol by own choice and no cardiac toxicity was detected on any patient.

Conclusions

Our results are consistent with those published in previous studies in terms of pCR rate and toxicity, however there was a high number of axillar dissections and for that reason we are working in an institutional protocol for the management of the axillary disease after NAT. Long term follow up is necessary to understand the real impact of pCR and to search for predictive indicators of the response to NAT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

22P - Correlation of muscle strength and quality of life in Indonesian breast cancer patients who underwent chemotherapy (ID 742)

Presentation Number
22P
Lecture Time
09:00 - 09:00
Speakers
  • Devina A. Halim (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotoxicity may cause sarcopenia, representing a loss of muscle strength and mass, which reduces quality of life (QoL) and physical function. Most of the breast cancer patients underwent chemotherapy reported significant aftereffects. However, the evaluation of muscle strength and QoL were still limited. Hereby, the study aims to evaluate the correlation between muscle strength and QoL in Indonesian breast cancer patients.

Methods

Participants were breast cancer women who underwent chemotherapy. Muscle strength was measured with a JAMAR handgrip. Breast cancer patients were evaluated their QoL from global health status and functional status which compromises the physical functioning (PF), role functioning (RF), emotional functioning (EF), cognitive functioning (CF) social functioning (SF). Assessment was done using the EORTC QLQ-C30. The correlation was analyzed with Pearson and Spearman correlation test.

Results

A population of 80 breast cancer women was involved, with a mean age of 47.39±7.0, median BMI of 23.15 (7.86-47.26) kg/m2 and median muscle strength of 16.5 (3-29) kg. The majority of the patients were stage 2 on diagnosis (76.3%). Median score for each domains were as followed, global health status=66.67(0-100); PF=93.33(0-133.33); RF=100(0-133.33); EF=83.33(33.33-100); CF=100(16.67-100); and SF=100(0-100). Correlations were found between muscle strength and global health status (r=0.282, p=0.011), PF (r=0.373, p=0.001), RF (r=0.26, p=0.02) whilst no correlation with EF (r=-0.68, p=0.549), CF (r=0.038, p=0.738), and SF(r=0.214, p=0.056).

Conclusions

Muscle strength was correlated with quality of life, specifically in global health status, physical functioning, and role functioning in breast cancer patients. Overall, nearly all of the domains have good outcomes. Further assessment in patients’ nutritional status and physical activity were needed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

23P - Oncotype DX RS correlation with clinicopathologic risk factors and chemotherapy: Follow up based on TAILORx study (ID 996)

Presentation Number
23P
Lecture Time
09:00 - 09:00
Speakers
  • Faroug S. Ali (Doha, Qatar)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Oncotype DX RS estimates the likelihood of recurrence and predicts the benefit from chemotherapy in early HR positive, node negative breast cancer. Patients are categorized into one of three tiers based on a calculated recurrence score (RS); low (<18), intermediate (18–30), and high (≥31–100). 2008 NCCN guidelines recommended adjuvant endocrine therapy for low RS, adjuvant chemoendocrine therapy for high RS. There was no clear chemotherapy recommendation for intermediate RS. In 2018 the TAILORx re-established RS categories; a score of less than 11 is low, 11-25 is intermediate and 26-100 is high, and provided evidence to treat patients with intermediate RS. We are Studying Oncotype Dx RS correlation with clinic-pathologic risk factors, and chemotherapy based on TAILORx tiers. We also looked the characteristics of patients with cancer recurrence.

Methods

Retrospective review of patients who had Oncotype DX test during 2012-2017 at National Cancer Center–Qatar.

Results

Of 54 patients studied 16(29.63%) had low RS, 32(59.26%) had intermediate RS, and 6(11.1%) had high RS. Univariate analysis showed that age (p<0.014), tumor grade (p<0.034), and Ki67% (cut-off 20%; p<0.013) were significantly different among Oncotype DX RS categories. There was no significant difference among Oncotype DX RS categories for tumor size (p<0.288) or PR status (cut-off 1%, p<0.3). Multivariate analysis showed that none of the clinical/pathological factors significantly predict the Oncotype DX RS. Chemotherapy was given to 1/16 (6.25%) patients with low, 7/32(21.9%) patients with intermediate, and 4/6 (66.7%) patients with high Oncotype DX RS (univariate analysis p<0.01). Tumor size was the only predictor of chemotherapy in multivariate analysis (OR 2.33 CI 0.33 - 3.86, p<0.020). 75% of patients who relapsed had RS 16-25, and were less than 50 years old in age.

Conclusions

Oncotype RS correlates significantly with individual clinical risk factors including age, tumor grade, Ki67%, chemotherapy treatment. Tumor size significantly predicts adjuvant chemotherapy. Breast cancer recurrence was noticed in younger patients with high intermediate RS (16-25), and adjuvant chemotherapy may be a reasonable option for these patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

24P - The Pink Vans: Bringing cancer screening closer to home (ID 193)

Presentation Number
24P
Lecture Time
09:00 - 09:00
Speakers
  • Frederic Ivan L. Ting (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

A global survey reported that among 15 Asian countries, the Philippines has the highest breast cancer mortality rate and the lowest mortality-to-incidence ratio. Studies have described socioeconomic factors as one of the major causes for the lack of access to early detection and treatment.

Methods

In response to this gap in the delivery of services to promote early cancer detection and in line with the Breast Health Global Initiative’s call for low and middle income countries to adopt breast cancer screening to the local context, the University of the Philippines – Philippine General Hospital Cancer Institute (UP-PGH CI) established the Mobile Breast Cancer Diagnostic Clinic Program, a first in the country -two pink vans that are fully equipped to reach far flung areas and provide breast cancer screening strategies are sent out to deliver services.

Results

In the first 6 months of the program’s existence, the pink vans were able to visit 3 strategically identified areas in the country. These three tours served a total of 189 women who all underwent mammography. Of these women, 18 had their suspicious lesions biopsied. Two-thirds of which were found to be malignant. These patients were then advised to follow-up at our institute for further work-up and management.

Conclusions

As the Philippine health department continues to emphasize clinical and self-breast exam as part of its breast cancer control program, efforts like the UP-PGH “Pink Vans” may eventually help supplement the gap in the country’s breast cancer screening endeavors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

25P - Identification of gene mutations in patients with breast cancer in a region located in the southeast of the European part of Russia (ID 268)

Presentation Number
25P
Lecture Time
09:00 - 09:00
Speakers
  • Alexander Sultanbaev (Ufa, Russia, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

It is known that breast cancer is a complex heterogeneous disease due to the presence or absence of overexpression of receptors on the surface of tumor cells that correlate with the presence of penetrant mutations. Malignant neoplasms are considered as genetic diseases if they are characterized by multiple mutations in the genome, or epigenetic changes at the DNA level. Hereditary forms of malignant neoplasms occupy a special position due to their frequent development at a young age.

Methods

The study was carried out using next-generation sequencing-NGS. A genetic blood test was performed on 30 patients with breast cancer.

Results

As a result, highly penetrant mutations in the BRCA1, BRCA2, CHEK2, PALB2, RAD50 genes were revealed in 30 patients. Of the total share of probands in the BRCA1 gene mutations were detected with a mutation of 5382insC - 12 patients, c.3143delG- 3. In the BRCA2 gene of patients mutation c.6621_6622del- in 2 people and s. -39-1_-39delGA- in 1 patient. Using IHC a basal-like subtype breast cancer was established in all patients. The mutations were detected in the CHEK2 gene in 5 patients: c.470T> C- in 3 patients with a luminal B (HER2 positive) subtype; c.444 + 1G> A- in 2 patients with HER2 positive (non-luminal). In the PALB2 gene of cases: all 4 people with a basal-like subtype with the 1592delT mutation. The mutations c. 2157delA were detected in the RAD50 gene in 3 patients: of which 2 had luminal B (HER2 negative), 1 had luminal A subtype of breast cancer.

Conclusions

A next-generation sequencing method has significantly improved the efficiency of detecting mutations in the genes responsible for hereditary breast cancer. Pathogenic mutations in the BRCA1 / 2, CHEK2, PALB2, RAD50 genes were found of patients with a hereditary feature of the disease (proband has 1 to 3 blood relatives with malignant neoplasms). The identification of highly penetrant mutations in probands allowed us to determine their relatives, the expectable carriers of mutations, which were informed of the need genetic counseling.

Legal entity responsible for the study

Sultanbaev Alexander.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

26P - Body mass index and clinical outcomes in Egyptian women with breast cancer: A multi-institutional study (ID 376)

Presentation Number
26P
Lecture Time
09:00 - 09:00
Speakers
  • Amrou Mamdouh Abdeen Shaaban (Shuwaikh, Kuwait)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The aim of this work was to evaluate the association between body mass index (BMI) and clinical outcomes among Egyptian breast cancer patients.

Methods

We reviewed the file registry of 629 patients with operable breast cancer regarding age, sex, height, weight, family history of breast cancer, menopausal status, tumor characteristics, TNM classification, and treatment during the period from January 2006 to December 2012. In our analyses, obesity was defined as a BMI of ≥30 kg/m2. The primary objective was to estimate the effect of obesity on the clinical outcomes of breast cancer patients including DFS and OAS.

Results

A total of 629 patients with a mean age of 51.1 years. Stage III and Stage II presented 52% and 46.6% respectively. Overweight and obese patients represent 60.5% of all patient population. there was no association between tumor stage, grade or menopausal status and BMI. Patients with normal BMI showed a median survival of 95.3 months [ CI: 54.6,136.06]. This was significantly higher than overweight and obese patients (p = 0.001). Nearly one-third of patients (29.1%) with normal BMI experienced disease relapse compared to 32.8% for overweight and obese patients, however, this was statistically not significant (0.097).

Conclusions

According to the results of this retrospective study, Obesity is an independent prognostic factor for OS in patients with operable breast cancer.

Legal entity responsible for the study

Minia University Hospital and Mansura University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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27P - Breast cancer primary site and laterality as predictive factors of prognosis: SEER based analysis for survival (ID 425)

Presentation Number
27P
Lecture Time
09:00 - 09:00
Speakers
  • Eman I. Zin Eldin (Menoufia, Egypt)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer prognostic factors vary from pathological grades, hormonal sensitivity, stage and LN metastasis. Results from recent studies discuss primary location as survival indicator but its significance still unclear. With SEER database registry in place, a rich source for data collection with differentiating breast cancer sites and primary location. With analysis of these data, the effect of cancer's primary origin on breast cancer survivorship would be more comprehensive.

Methods

Using SEER*stat 8.3.6 program, Based on Incidence - SEER Research Data, 9 Registries, Nov 2019 Sub (1975-2017), patients diagnosed with breast cancer (site recode ICD-O-3) between 1975-2017 are selected. Case listing session was done with extraction patients year of diagnosis, survival time in months, laterality, and primary site. Cox regression was done using IBM SPSS statistics 25. p-value <0.001 is considered significant.

Results

720272 patients were involved in analysis (50.9% left:49.1% right origin of primary). Median survival time for the cohort was 185 months(95% CI:184.4:185.5). Left side malignancy showed a significantly less positive effect on survival than right originated ones (HR, 0.988; 95% CI, 0.982–0.995). The upper and lower inner quadrants show a significantly higher effect on survival (HR, 1.877; 95% CI, 1.797–1.960) and 1.761(1.685). (HR, 1.761; 95% CI, 1.685–:1.842) respectively P-value <0.001.

P-value HR 95.0% CI for HR
Lower Upper
Nipple Reference
Central portion of breast <0.001 1.454 1.391 1.521
Upper-inner quadrant of breast <0.001 1.877 1.797 1.960
Lower-inner quadrant of breast <0.001 1.761 1.685 1.842
Upper-outer quadrant of breast <0.001 1.567 1.501 1.635
Lower-outer quadrant of breast <0.001 1.711 1.637 1.788
Axillary tail of breast <0.001 1.142 1.078 1.211
Overlapping lesion of breast <0.001 1.680 1.610 1.754
Breast, NOS <0.001 1.350 1.293 1.410

Hazard ratios for primary site of breast cancer: Cox regression analysis Optimal cut-offs were determined with a maximal chi-square method.HR: hazard ratio; CI: confidence interval; NOS: not otherwise specified

Conclusions

Upper and lower inner quadrants show the best survival for patients diagnosed with breast cancer. The primary site of malignancy in breast cancer appears to be a good predictive value of survival and can be used as a rough method to predict patients` prognosis. More Data extraction, analysis, and interpretation of overall and cause-specific survival are recommended for more knowledge about the primary site in depth.

Legal entity responsible for the study

Mohamed Alaa Gouda.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

28P - Breast cancer care services at Nilai Medical Centre: A Malaysian experience (ID 496)

Presentation Number
28P
Lecture Time
09:00 - 09:00
Speakers
  • Ratnavelu Kananathan (Nilai, Negeri Sembilan, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Introduction and Rationale. Nilai Medical Centre was established on 1999 in Nilai Negeri Sembilan. In a partnership with Malaysian Health Travel Council data was collected prospectively using the HPMRS platform. HPMRS is a locally developed data base system to measure health care performance and reporting. For the purpose of measuring breast cancer performances, we mostly adopted the performances measures developed and used by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comphressive Cancer Network and National Accreditation Program for Breast Cancer.

Methods

Data Data was reported to HPMRS by year of reporting according to the centre participating in MHTC’s PHTE program. A total of 226patients were reported from 2010 till 2014. 76 patients were ineligible for inclusion while 53 patients had incomplete data for analysis and were excluded from analysis.

Results

The Aged ranged from 33 to 79 with a mean of 51years, 43% were aged <50years. 41% Chinese, 38% Malays and 20% Indians. 41% Early Breast Cancer, 35% Locally Advanced Cancer and 16% metastatic Breast Cancer. Receptor states were 55% positive for ER,43% PR and 31% for HER2. 19% had Triple negative breast cancer. Breast Cancer Care Performances The overall Breast Cancer care results was 98%. A 98% composite score means that the centre provided an evidence based Breast Cancer Treatment 98 times for ever 100 opportunities. Performances varied from as low as 50%(Trastuzumab treatment ) to a perfect score of 100% (Pathology report confirming malignancy, surgical treatment and radiotherapy) Survival Data The 5 years overall survival 99% Stage I, 83% Stage II,36% Stage III and 28% Stage IV. The relative survival at 5years was 99% Stage I and 97% Stage II indicating these patients were practically cured of their disease. This was far better then the results reported in Malaysian Study on Cancer survival of 87% in Stage I and 80% in Stage II. In the other stages NMC survival was 81.9% in Stage III and 50.4% in stage IV compared with 59% in Stage III and 23.3% in Stage IV in the Malaysia Study. NMC results were comparable with the SEER results( 2008 till 2014) as Early stage 99%,Localized Stage 85% and Distant stage 27%.

Conclusions

The results will set as a base line for future measurements.

Legal entity responsible for the study

Kananathan R.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

29P - Factors affecting breast self-examination (BSE) behaviour among female high school students in Denpasar City, Bali (ID 592)

Presentation Number
29P
Lecture Time
09:00 - 09:00
Speakers
  • Cindy G. Trisina (Denpasar, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is the most common type of cancer for women worldwide and in Indonesia. Breast cancer patients in Bali, especially in Denpasar, are mostly diagnosed during advanced stage. Among those late stage diagnosis, 40-50 years old being the most prevalent with young women (<40 years old) being above average in prevalence. Early detection such as Breast Self Examination (BSE) is very crucial to prevent late stage detection. Therefore, we aimed to evaluate factors affecting BSE behavior among female high school students in Denpasar City, Bali Province, Indonesia.

Methods

A pre-experimental cross-sectional study-based community was conduct on 11 January 2020 in Denpasar, Bali. The data is collected using a validated questionnaires to evaluate knowledge, attitude, behavior, information exposure, parent support, and peer support as factors affecting BSE behavior among female high school students. Data is analyzed using chi-square with p-value ≤0.05 is categorized as significant.

Results

82 respondents were involved in this study with a mean age of 15.93 ± 0,798 years. Mostly the students have high knowledge (63.4%), good attitude towards BSE (51.2%), BSE information exposed (58.5%), low parent support towards BSE (57.3%), and low peer support towards BSE (74.4%). The highest significant factor is knowledge (p= 0.001, OR=6.500), followed by BSE information exposed (p=0.003, OR=4.667), and peer support (p=0.023, OR=3.185).

Conclusions

We conclude that factors affecting BSE behavior among female high school students in Denpasar, Bali are knowledge, BSE information exposed, and peer support. We suggest greater attention in improving students’ knowledge, expose more information about BSE, and educate peer support towards BSE among female high school students in Denpasar, Bali.

Legal entity responsible for the study

Badan Semi Otonom Komunitas Mahasiswa Peduli Kanker Fakultas Kedokteran Universitas Udayana.

Funding

Badan Semi Otonom Komunitas Mahasiswa Peduli Kanker Fakultas Kedokteran Universitas Udayana.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

30P - Male breast cancer: A rural based peripheral cancer center experience (ID 759)

Presentation Number
30P
Lecture Time
09:00 - 09:00
Speakers
  • SACHIN KHANDELWAL (SANGRUR, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Male breast cancer (MBC) is an uncommon malignancy with an estimated incidence of less than 1 % of all breast cancer cases. It is a disease of elderly arising in 6th to 7th decade. Patients usually present at an advanced stage with early skin and nodal involvement. Age, testicular disorders, liver cirrhosis, exogenous estrogens, BRCA -2 mutations are proposed etiological factors. There are four Population based cancer registries (PBCR) in Punjab, India. Amongst them two are predominantly urban (Chandigarh and SAS Nagar) and two are predominantly rural (Sangrur and Mansa). Sangrur PBCR is based at Homi Bhabha Cancer Hospital (under aegis of Tata Memorial Center, Mumbai). The aim of this study is to look into the incidence and clinico-pathological characteristics of M.B.C at our institute, mainly catering to a rural population.

Methods

A total of 1735 breast cancer cases registered over a period of 4 ½ years from January 2015 to July 2019 were screened. Online records were accessed.

Results

A total of 34 M.B.C cases were identified amounting for 1.9% of all breast cancer cases. All patients were from Punjab except one. 44.1% were from district Sangrur. If we look at district wise ratio of MBC to total breast cancer cases then Barnala (2.3) is followed by Mansa (2.1) followed by Sangrur (2.09). Mean Age was 62.5 years. Mean BMI (N=20) was 23.9. Family history was not significant in any case. Tumor was localized to right in 64.7 % cases. Most of the tumors were central in location (70.6%). Main complaint was lump in 58.8%. 16 patients were metastatic,10 were LABC, 8 were early stage. All were infiltrating ductal carcinoma. 27 were ER +ve, 25 were PR +ve, 1 was her2neu positive, 1 was Triple negative. 7 patients were Luminal A, 8 were Luminal B, 1 was Basal, 6 were unknown due to missing information,12 were Luminal A/B. 13 patients were treated radically, 9 were palliative & 12 patients defaulted. 4 patients with oligo-metastatis treated radically were alive at last presentation. 2 patients underwent palliative mastectomy.

Conclusions

Our ratio of M.B.C to breast cancer cases is 1.9 % which is higher than average of 1%. Study period in our series is only 4 1/2 years unlike others, usually more than a decade, with equivalent number of cases. Unlike other studies our burden of metastatic disease was more.

Legal entity responsible for the study

Sachin Khandelwal.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

31P - The prognostic value of pre-treatment peripheral neutrophil-lymphocyte-ratio (NLR) and its correlation with mutant p53 expression in Indonesian triple negative breast cancer patients (ID 800)

Presentation Number
31P
Lecture Time
09:00 - 09:00
Speakers
  • Rosita Y. Purwanto (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-Negative Breast Cancer (TNBC) represents an aggressive phenotype among other breast cancer subtypes with worst prognosis due to abundant inflammatory process. Recent pre-clinical study suggested a correlation between p53 inactivation and systemic inflammation response in driving breast cancer progression. In this study, we evaluated the prognostic value of pre-treatment NLR and its association with mutant p53 expression.

Methods

TNBC patients treated in of Dr. Sardjito General Hospital during 2014-2017 were retrospectively analyzed. Receiver Operating Curve (ROC) was utilized to determine the NLR cut off value and Kaplan Meier survival analysis was used to evaluate the 3-years overall survival (OS). To examine the correlation of NLR and p53, chi-square and independent t-test analysis were applied. Multivariate analysis was done using Cox Proportional Hazard Regression Model with adjustment for age, BMI, clinical staging, histological grading, subtypes, and therapy.

Results

A total of 53 TNBC patients were included in this study. The cut off value used to classify NLR into high and low NLR was 1.67 (AUC: 0.720, 95%CI: 0.581-0.859, p: 0.007, sensitivity: 87.1%, specificity: 50.0%). Mutant p53 expression was associated with high NLR (p= 0.013) with significant difference (Mean difference: 0.611, 95%CI: 0.425-1.179, student’s t-test p: 0.036). Patients with high NLR showed worse 3-years OS than patients with low NLR (Median OS±SE (months): 21.205±2.356, 95%CI: 16.588-25.823 vs unreached, p: 0.006). NLR was an independent prognostic factor of TNBC based on multivariate analysis (HR: 3.705, 95%CI: 1.176-11.666, p: 0.025).

Conclusions

Mutant p53 expression was associated with high NLR and, furthermore, NLR was an independent prognostic marker for TNBC. Therefore, this combination has the potential to stratify TNBC patients’ risk and further study is needed to formulate the stratification system.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

33P - FDG-PET predictivity of pathological axillary nodal status in carcinoma breast-upfront and post-neoadjuvant chemotherapy (NACT) setting (ID 161)

Presentation Number
33P
Lecture Time
09:00 - 09:00
Speakers
  • Krithikaa Sekar (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

FDG PET is used in staging, early prediction of treatment response, monitoring metastatic tumours and in disease status assessment post completion of treatment. In patients undergoing upfront surgery, a significant standardized uptake value (SUV) is associated with pathological node positivity. In patients receiving anterior chemotherapy, studies have shown that a reduction in size and SUV of primary tumour or involved node predicts response to therapy. However based on our observation, the predictive value of PETCT appeared to differ between the upfront setting and post-neoadjuvant chemotherapy (NACT) setting. Our study compares the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET in predicting pathological axillary nodal involvement in 50 upfront surgery and 50 post-NACT patients.

Methods

This study was conducted between the years 2015 to 2016. Clinical, histopathological and radiological details were obtained from patient records. 50 upfront surgery and 50 post-NACT patient details were reviewed for PETCT nodal status and histopathological nodal status and the following parameters analysed. 1)Sensitivity; 2)Specificity; 3)Positive Predictive Value; 4)Negative Predictive Value

Results

In upfront surgery cases the total number of TP was 21, FP was 2, FN was 12 and TN was 15. In post NACT setting, it was 5, 1, 10 & 34 respectively.

Upfront PETCT Post NACT PETCT
Sensitivity 63.6% 33.3%
Specificity 88.2% 97.1%
Positive Predictive Value 91.3% 88.3%
Negative Predictive Value 55.3% 77.2%

Conclusions

Although metabolic response monitoring post chemotherapy is a useful tool,the sensitivity appears to be lower in predicting pathological node positivity. That is, the proportion of patients with positive pathological node having PET positivity appears to be lower. A practical application of the same would be, to complete all cycles of chemotherapy prior to surgery, irrespective of an interim PETCT complete nodal response, to attain maximal Pathological Complete Response rates.To conclude, the rate of PETCT predictivity of pathological axillary nodal positivity appears to differ between upfront surgery and post-NACT setting.

Legal entity responsible for the study

Krithikaa Sekar.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

34P - Clinical significance of neoadjuvant dose-dense chemotherapy for II and III stage breast cancer: A meta-analysis of published studies (ID 626)

Presentation Number
34P
Lecture Time
09:00 - 09:00
Speakers
  • Meng chen Liu (Shijiazhuang, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For Ⅱ and Ⅲ stage breast cancers (BCs),neoadjuvant chemotherapy (NCT) is typically the initial treatment.However, there is no evidence to support an improvement in efficacy with dose-dense (DD) chemotherapy (CT) in this setting. Results from clinical trials of neoadjuvant DD-CT in patients with breast cancer are inconsistent.This systematic review evaluates whether DD-CT was more effective than the standard-schedule CT.

Methods

This meta analysis included all comparative prospective and retrospective studies published in Pubmed, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science and the CNKI databases over the past 10 years.The studies that compared the DD-CT with a standard-schedule CT met our inclusion criteria.The primary outcomes were pathologic complete responses (ypT0N0M0: pCR). The secondary outcomes were disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) for pCR and Risk ratios (RRs) for DFS and OS were estimated and pooled.

Results

Eight studies involving 2477 patients were included in this meta-analysis. Of these, 1214 patients were treated with DD-CT and 1263 patients were treated with CT. The primary outcomes included 8 studies while the secondary outcomes included 7 studies. The pooled rates of the pCR were 19.4% and 11.9% in the experimental and control arms respectively. A significant increase in the pCR [OR= 1.74, 95% confidence interval (CI) 1.38–2.18, P < 0.00001] was noted with DD-CT. Dose-dense treatment also improved DFS[RR= 0.78, 95%CI 0.63–0.98, P = 0.03] and OS [RR= 0.81, 95%CI 0.68–0.96, P = 0.01]. However there was some heterogeneity.Similar results were observed in the further analysis, which was supported by our sensitivity analyses.

Conclusions

The meta-analysis demonstrated that DD-NCT significantly increased the pCR of Ⅱ and Ⅲ stage breast cancer compared with standard-schedule CT. Adjuvant dose-dense regimens can also improve DFS and OS.Taking into account the actual improvement in clinical efficacy,prognostic valueand the acceptable safety profile, DD-CT can be considered a standard approach for neoadjuvant therapy in Ⅱ and Ⅲ stage breast cancer.

Legal entity responsible for the study

The Fourth Hospital of Hebei Medical University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

35P - Pathological response to weekly nabpaclitaxel and carboplatin followed by anthracycline regimen in triple negative breast cancer (ID 959)

Presentation Number
35P
Lecture Time
09:00 - 09:00
Speakers
  • Goteti Sharat Chandra (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pathological complete response (pCR) is considered a potential surrogate marker for survival in triple negative breast cancer (TNBC), thus attracting strategies to achieve higher pCR. Addition of carboplatin to standard neoadjuvant chemotherapy regimen has been seen to increase pCR.

Methods

We aimed to evaluate efficacy of nab paclitaxel and carboplatin followed by dose dense anthracycline regimen by pCR in women with locally advanced tnbc. Patients with confirmed stage 2 or 3 were included. Hormone receptor and her 2 neu receptor status was confirmed by IHC and/or FISH. Patients received 12 weekly nab paclitaxel 125 mg/m2 plus carboplatin AUC 2 followed by dose dense doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 for 4 cycles and subsequent surgery. pCR was defined as absence of any disease in breast and axilla on surgical specimen. Secondary end points were breast conservation rates, progression free survival and toxicities.

Results

35 patients with confirmed stage 2 (20%) and stage 3 (80%) were treated between January 2017 and December 2020.The median age of patients was 48.7 years (26 – 71). pCR was achieved in 62.8 % (22) and remaining patients had partial response 34.2% (12). One patient showed stable disease on pathological specimen. Breast conservation surgery (BCS) was possible in 60 % (21). Of those who achieved pCR, 68 % (15) underwent BCS. Grade 3/4 toxicities were fatigue 2.8 % (1), thrombocytopenia 8.5 % (3), nausea/vomiting 2.8 % (1), peripheral neuropathy 2.8 %(1), febrile neutropenia 17 % (6) and anemia 14.2% (5). Hematological toxicity was tackled with reduction of carboplatin dose to AUC 1.5. Dose modifications were done in 63 % of patients. Anemia (74.2%), neutropenia (80%) and thrombocytopenia (71.4%) were most common all grade toxicities. After a median follow up of 25 months, median progression free survival was 68 % as per Kaplan-Meier analysis.

Conclusions

Nab paclitaxel and carboplatin followed by anthracycline regimen as neo adjuvant regimen led to impressive pCR rate of 62.8% in our study. Regimen was tolerated well with necessary dose adjustments showing good response rates with a trend towards increased progression free survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

36P - Survival in patients with contralateral breast cancer (ID 962)

Presentation Number
36P
Lecture Time
09:00 - 09:00
Speakers
  • Sergey Kamishov (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Survival in patients with contralateral breast cancer Kamishov S.V., Izrailbekova K.Sh. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent. Survival data are not readily available in many developing countries due to inadequate information systems to collect reliable data on cancer mortality. Not all cancer patients die from cancer. Thus, cancer and other causes of death act independently or simultaneously. A cohort study was conducted to identify risk factors for contralateral breast cancer and to determine whether there was any significant difference in survival among patients with unilateral breast cancer (UBC) and patients with primary contralateral breast cancer (PCBC).

Methods

The study group consisted of patients with breast carcinoma as the first invasive primary cancer, diagnosed in 2012-2019 (n = 3492) at the Republican Special Medical Center for Medical and Rehabilitation of Uzbekistan, Tashkent). They were under surveillance until December 31, 2019. All patients undergoing treatment are monitored in accordance with the observation protocols of the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan In this study, the follow-up loss was 10% in UBC patients and 7.5% in PCBC patients.

Results

A total of 3492 cases of breast cancer were diagnosed at the RSPMCHR from 2012-2019. The analysis included all patients with UBC who did not develop a second cancer (n = 3163) and patients with PCBC who developed contralateral breast cancer (n = 67). The relative survival rates between younger, middle-aged, and older women with PCBC were significantly different from each other (p = 0.001). The differences in the relative survival rates of young, middle-aged and older women with UBC were not statistically significant (p = 0.4).

Conclusions

Despite the small sample size, the present study shows that early diagnosis has a survival advantage in breast cancer. In addition to organizing mammographic screening, in developing countries, educational programs are needed to raise awareness of cancer in order to detect breast cancer at an early stage and reduce mortality.

Legal entity responsible for the study

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent.

Funding

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

37P - Correlation between haematological toxicity with quality of life in breast cancer patients after first-cycle chemotherapy (ID 503)

Presentation Number
37P
Lecture Time
09:00 - 09:00
Speakers
  • Felix Wijovi (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy, as one of the main therapies to treat breast cancer, may result in undesirable side effects. It may disrupt the haematological system and cause disorders as a result of chemotoxicity. This condition may lead to a declining in Quality of Life (QoL) of the patients. There were limited data reported from Indonesia about the correlation between haematological chemotoxicity and QoL. Thus, the aim to find the association between them.

Methods

This was a cohort-prospective study which includes 50 breast cancer patients who undergone first-cycle of chemotherapy. Patients who had haematological abnormalities and poor quality of life before chemotherapy were excluded. Patient’s QoL was measured by QLQ-BR23 questionnaire which includes body image (BI); sexual functioning (SF); sexual enjoyment (SE); future perspective (FP); and functional total (FT). Haematological chemotherapy toxicity was determined by the number of haemoglobins, leukocytes count and platelet count. Chemotherapy toxicity is graded from 0 (no toxicity) to 5 (death) according to the National Common Institute Common Terminology Criteria for Adverse Events. Correlation is analysed with Pearson Correlation using SPSS version 25.0.

Results

65 patients were included in this study (mean age 46.98 ± 9.05). The correlation between haematological chemotoxicity and BI; SF; SE; FP; and FT were described as follow: Hb r = -0,3; -0.251; -0.498; -0.345; and -0.61 respectively, with p = 0.08; 0.044; 0.01; 0.283; and 0.02 respectively. Leukocyte r = -0.41; -0.121; -0.128; -0.7; -0.3 respectively, with p = 0.01; 0.3; 0.3; 0.02; 0.05 respectively. Platelet r = -0.123; -0.31; -0.7; -0.9; -0.042 respectively, with p = 0.3; 0.03; 0.04; 0.1; 0.05 respectively.

Conclusions

We found that Hb and platelet level is significantly correlated with sexual functioning, sexual enjoyment, and functional total. Meanwhile, the leukocyte level is significantly correlated with body image, future perspective, and functional total.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Breast cancer, locally advanced (ID 1142)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

38P - Evaluation of the prognostic value of innate immunity-related biomarkers in early breast cancer (BC) (ID 872)

Presentation Number
38P
Lecture Time
09:00 - 09:00
Speakers
  • Veronica Martini (Novara, Italy)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

CD47 and SIRPα (signal-regulatory protein) are tumor biomarkers of innate immunity, expressed on cancer cells and tumor associated macrophages (TAMs); their interaction provides a “don’t eat me” signal that impairs phagocytosis. The relationship between CD47/SIRPα expression and BC aggressiveness has been investigated, however, its prognostic role is not clarified. With these premises, we have assessed the distribution and the possible prognostic value of CD47/SIRPα expression in early BC.

Methods

To verify our hypothesis, we first used in silico data from GOBO and GEPIA, two publicly available datasets: GOBO is a public repository containing microarray data (Affymetrix U133A) from 1881 early BC patients, with a median follow up of 120 months. GEPIA is a web server for analysing RNA expression data of tumours and normal samples from the TCGA and the GTEx projects, by a standard processing pipeline. Immunohistochemical (IHC) analyses were retrospectively performed on formalin-fixed paraffin embedded tissue (FFPE) samples in a cohort of 105 BC patients referred to our institution. The association between CD47 and SIRPα expression levels and outcome was evaluated using the χ2 test. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier life table method.

Results

In silico data showed that CD47 and SIRPα are preferentially expressed in triple negative (TN) BC, as compared to other BC subtypes (p< 0.0001). CD47 upregulation is associated to a worse OS only in Luminal A BC (GOBO p<0.001, n= 189 patients). By IHC analysis in our retrospective series, CD47 was overexpressed in 80% of TNBC and in 56% of Luminal BC samples. Of note, SIRPα was expressed in 20% of TAMs and in 50% of TN BC samples.

Conclusions

Biomarkers of innate immunity are represented but differently expressed in the different BC subtypes; IHC analyses are ongoing to consolidate this result and to assess their prognostic role in our patient cohort. Final analyses will be presented.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

39P - CSF-1R inhibitor (C019199) enhances antitumor effect in combination with anti-PD-1 therapy on murine breast cancer models (ID 822)

Presentation Number
39P
Lecture Time
09:00 - 09:00
Speakers
  • Jiani Zheng (Xiamen, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colony-stimulating factor-1 (CSF-1) is the primary regulator of mononuclear phagocytic cells. CSF-1 plays an important role in recruiting macrophages to tumor environment. Overexpression of CSF-1 and its ligand, colony-stimulating factor-1 receptor (CSF-1R), have been reported to be associated with the development of various types of cancers, such as breast, ovarian, and colorectal cancer. This study aims to investigate the treatment effects of a new CSF-1R inhibitor named C019199 in murine breast cancer (BC) models when administered alone or in combination with anti-PD-1 antibody.

Methods

Inhibition of CSF-1R was investigated in the murine bone marrow derived macrophages (BMDMs) for cell-based assay. Furthermore, the immunocompetent Balb/c mice were subcutaneously implanted 4T1 breast cancer cells in the right flank. Mice were randomized into groups of 9 and treated with C019199 (orally, 30 mg, 60mg or 120 mg/kg/d), either alone or in combination with anti-mouse PD-1 antibody (intraperitoneally, 10 mg/kg). 1 of 9 groups was treated with single-agent Docetaxel (intraperitoneally, 10 mg/kg). The animal body weight and tumor growth were monitored twice a week. Results were analyzed by 2-way ANOVA with Bonferroni's test.

Results

1. C019199 inhibited the murine colony-stimulating factor-1 receptor (CSF-1R) with an IC50 of about 8.0nM in cell-based assay. 2. C019199 inhibited tumor growth in murine BC models. The combination of C019199 and anti-PD-1 had better synergistic antitumor efficacy than single-agent. Balb/c mice implanted 4T1 cells were treated with C019199 alone or combined with anti-PD1 for 14 days. The antitumor efficacy and treatment detail (Table) were detected.

Effect of C019199 on body weight and tumor size in murine 4T1 breast cancer models

Group Administration regimen Tumor size (mm3,Mean±SEM) Rate% of average body weight change
Day 0 Day 14
Vehicle QD x 14 67.11 ± 3.01 1705.69 ± 130.96 13.76%
Anti-mPD-1 Day 0, 3, 7, 10 66.82 ± 3.05 1343.55 ± 118.65 16.43%
Docetaxel Day 0, 7 66.88 ± 3.11 1023.00 ± 68.19**** 4.21%
C019199 QD x 14 67.07 ± 3.17 1074.32 ± 59.31**** 11.01%
C019199 QD x 14 66.76 ± 3.05 927.24 ± 65.68**** 7.97%
C019199 QD x 14 66.69 ± 2.99 671.71 ± 62.56**** 2.18%
Anti-mPD-1 Day 0, 3, 7, 10 66.62 ± 2.94 1079.65 ± 64.05**** 13.25%
C019199 QD x 14
Anti-mPD-1 Day 0, 3, 7, 10 66.53 ± 2.86 794.21 ± 105.82**** 10.50%
C019199 QD x 14
Anti-mPD-1 Day 0, 3, 7, 10 66.41 ± 2.72 619.62 ± 25.10**** 4.85%
C019199 QD x 14

*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 compared with vehicle group. SEM, standard error of mean.

Conclusions

C019199 is a new tyrosine kinase inhibitor of CSF-1R. Single-agent C019199 showed dose-dependently inhibition in murine 4T1 BC tumors. C019199 combined with anti-PD-1 had better antitumor efficacy than C019199 alone. Assessed by animal body weight, such combination therapy was well tolerated. The mechanisms of C019199-mediated immunomodulatory effects in combination with anti-PD-1 need further exploration.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

40P - Molecular subtypes and imaging phenotypes of breast cancer: MRI (ID 904)

Presentation Number
40P
Lecture Time
09:00 - 09:00
Speakers
  • Yulduz N. Khatamovna (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study aimed to examine MRI dynamic contrast-enhanced (DCE) imaging in various histological and molecular biological types of breast cancer.

Methods

To solve the set tasks, a clinical and instrumental examination was carried out of 70 women with a verified diagnosis of breast cancer who were examined and treated at the RSSPMCO&R in 2017–2019. The age of the patients was 26–75 years (mean age - 49.0 ± 2 years).

Results

For luminal A cancer (22 of 70 cases), the following MR signs were revealed: nodular formations more often had an irregular shape - 21 (95.5%), irregular (59.1%), less often spicular contours (27.3%). In 16 of 22 cases, a ring-shaped contrasting pattern was noted. Type III intensity-time curve at MRI with DCE was found in all 22 patients with luminal A subtype of breast cancer. It should be noted that all additional MR signs (retraction of the nipple, thickening and deformation of the skin over the formation) were found in luminal subtype A. The luminal B-subtype was detected in 20 patients (28.6%), with Her2/neu-positive luminal B-subtype noted in 12 patients, and Her2/neu-negative subtype in 8 cases. For these two subtypes of the masses visualized on MRI images were the same (irregular shape with indistinct contours, annular contrasting), but 4 of 12 patients with luminal Her2/neu-positive subtype had type II on MRI with DCE. The same type of curve was observed in 5 out of 11 patients (45.5%) with Her2/neu-positive breast cancer. At the same time, with luminal, subtype, luminal, Her2/neu-negative subtype, and three cases of negative breast cancer, type III of the dynamic contrast curve was always observed. Consequently, type II of the curve was observed only with negative Her2/neu types. In our studies, in 53% of triple-negative subtypes breast cancer was displayed on MR images with a rounded-oval or lobular shape, and in 17.6% with clear smooth (smooth) contours. But type III “intensity - time” curve, noted according to MRI data with DCE, testified to the malignant process in all 17 patients with triple-negative breast cancer.

Conclusions

Our studies have shown that the pathologically determined degree of differentiation of breast cancer and immunohistochemical types and subtypes affect the visualized morphological characteristics and its functional features, assessed by MRI with DCE.

Legal entity responsible for the study

Nishanova Yulduz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

42P - Impact of germline mutations on breast cancer prognosis in Kazakh population (ID 1029)

Presentation Number
42P
Lecture Time
09:00 - 09:00
Speakers
  • Dilyara Kaidarova (Almaty, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer (BC) shows a high incidence both in Kazakhstan and worldwide. Presence of BRCA1 and BRCA2 genes defects, as well as non-BRCA genes can increase the risk of BC and they are still under study. There is evidence of the effect of germline mutations on the survival outcomes of breast cancer patients, according to the molecular characteristics of the tumor in different subgroups.

Methods

The study enrolled 235 unrelated patients from the Kazakh population (the average age 34.25 ± 4.56) with BC. Genomic DNA was obtained from peripheral blood and sequencing was performed using TruSight Cancer Kit on the MiSeq platform.

Results

Bioinformatics analysis of NGS data identified 64 pathogenic variants, the heterozygous state were found in 62 (26.4%) patients, 8 (12.5%) variants were not previously described in databases.The most frequent pathogenic mutations were in the genes BRCA1 (24 variants (37.5%) and BRCA2 (18 (28.1%)). Additional pathogenic variants were identified in the non-BRCA genes (APC, ATM, BLM, CHEK2, PALB2, TP53, ERCC2, FANCA, FANCM, NBN, PMS1, PMS2, SDHB and XPA). 84 of the patients (43.3%) had early stage BC, 101 (52.0%) locally advanced, 9 (4,6%) with advanced forms of BC. 45 (23.2%) had disease progression after complex treatment: bone mets in 10 cases, 6 patients had liver mets, 11 lung and 6 patients had brain mets, 12 had combination of different metastases- visceral crisis. 6 cases showed cancer-related death, 5 of them had metastasis in CNS. Luminal A and B was in 27 (13.9%) and 81 (41.7%) cases, 20 (10.3%) patients had Her2-enriched, and 64 (32.9%) had triple-negative subtype of tumor according IHC. The triple-negative molecular subtype of the tumor was found most in the BRCA1-associated group, almost two times higher than in the group of patients without pathogenic mutations (58.3% versus 29.5%, χ2 = 9.45, p = 0.002), the difference is statistically significant. Her2-enriched and triple-negative subgroups had worse OS than Luminal subtypes (hazard ratio, HR 1.20 95% CI: 1.12-1.51) and worse OS, showing 3 patients with a combination of pathogenic BRCA1/2, CHEK2, PALB2, TP53 mutations.

Conclusions

The presence of germline mutations in combination with aggressive subtypes significantly decreases overall survival in young women with breast cancer in the Kazakh population.

Legal entity responsible for the study

Kazakh Institute of Oncology and Radiology.

Funding

Ministry of Healthcare of Kazakhstan.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO2 - Trastuzumab associated cardiotoxicity presenting with features of Left anterior descending occlusion on Echocardiography - a Young oncologist case report. (ID 214)

Presentation Number
YO2
Lecture Time
09:00 - 09:00
Speakers
  • Rahul D. Arora (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

Breast cancer, metastatic (ID 1143)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

50P - Efficacy and safety analysis of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer: A retrospective study (ID 867)

Presentation Number
50P
Lecture Time
09:00 - 09:00
Speakers
  • Yijia Hua (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lapatinib has shown effectiveness in treating HER2-positive metastatic breast cancer, but therapies after lapatinib resistance are still controversial. In this retrospective study, we assessed the efficacy and safety of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer.

Methods

From August 2018 to March 2020, 76 HER2-positive metastatic breast cancer patients who previously failed by lapatinib received pyrotinib in four hospitals. The primary endpoint was investigator-assessed progression-free survival (PFS) per Respond Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoint was the overall survival (OS) and safety of pyrotinib.

Results

66 (86.8%) patients received pyrotinib immediately after lapatinib and 10 (13.2%) received pyrotinib following one or more other therapies. The median PFS of pyrotinib was 8.0 months (95%CI 5.1-10.9) and OS has not reached. Objective response rate (ORR) was 17.1%, and clinical benefit rate (CBR) was 60.5%. Patients who benefited from lapatinib ≥6.0 months were found to have a longer PFS (P=0.034; stratified hazard ratio [HR] 0.534, 95%CI 0.293-0.975). In patients who had received lapatinib in 3 or later line therapy (35, 46.1%), the median PFS of pyrotinib was 9.9 months (95%CI 6.97-12.83) and was relevant to whether lapatinib PFS had reached 6.0 months (P=0.044; HR 0.412, 95%CI 0.167-1.013). No relations were detected between pyrotinib PFS and estrogen receptor (ER) status, trastuzumab resistance, brain metastasis or the sequential use of pyrotinib. In patients who had received lapatinib earlier (41,53.9%), the median PFS of pyrotinib was 6.4 months (95%CI 3.57-9.23). No relevant factors were observed. There was no difference in PFS between these two groups with different lapatinib lines. Toxicity profiles were similar in both groups. The most common adverse effects were diarrhea (34, 44.7%) and hand-foot syndrome (10, 13.2%).

Conclusions

Pyrotinib could improve the survival of HER2-positive metastatic breast cancer patients after the failure of lapatinib. For patients who benefited from lapatinib ≥ 6.0 months in 3 or later line therapy, pyrotinib could provide a clinically meaningful longer PFS.

Legal entity responsible for the study

The authors.

Funding

National Key Research and Development Program of China (ZDZX2017ZL-01), High-level Innovation Team of Nanjing Medical University (JX102GSP201727), Wu Jieping Foundation (320.6750.17006), Key Medical Talents (ZDRCA2016023), 333 Project of Jiangsu Province (BRA2017534 and BRA2015470), The collaborative innovation center for tumor individualization focuses on open topics (JX21817902/008) and Project of China key research and development program precision medicine research (2016YFC0905901).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

51P - Real world outcomes in elderly women with HER2-positive advanced breast cancer (ID 547)

Presentation Number
51P
Lecture Time
09:00 - 09:00
Speakers
  • Nicole Evans (Box Hill, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The development of anti-human epidermal growth factor receptor 2 (HER2) therapies has significantly improved disease outcomes in patients with HER2-positive advanced breast cancer (ABC). However, elderly patients are largely under-represented in clinical trials. We examined treatment patterns and outcomes in an elderly (defined as ≥70) ‘real world’ Australian population.

Methods

Data was extracted from the Treatment of Advanced Breast Cancer in the HER2-positive Australian Patient (TABITHA) multi-site clinical registry, and patients stratified according to age (<70 and ≥70 years). Descriptive statistics were used to report baseline characteristics and compared using T-tests and Chi square analyses. Treatment duration and overall survival were calculated via the Kaplan-Meier method.

Results

We identified 319 patients, including 67 patients (21%) aged ≥70 years. Older patients were more likely to have an Eastern Cooperative Oncology Group performance status of ≥2 (16% vs 3%; p<0.001) and a Charlson Comorbidity Index of ≥2 (13% vs 7%; p<0.001). There were no significant differences in hormone receptor status, de novo metastatic presentation, or presence of visceral disease. A similar proportion of patients in each group received first line HER2-directed therapy, and the duration of therapy was not significantly different. Despite no difference in the proportion of patients who received first-line chemotherapy, older patients demonstrated shorter chemotherapy durations (2.7 months vs 3.5 months; p<0.02). Median overall survival was significantly longer in younger patients (82.4 months vs 42.3 months; hazard ratio, 0.50; 95%CI, 0.29-0.87; p<0.001). In the first-line setting, adverse events rates were higher in the older group (34% vs 20%; p=0.04), including cardiotoxicity (7% vs 0.9%; p=0.02), and on-treatment deaths (5% vs 0%; p=0.01).

Conclusions

Elderly patients with HER2-positive ABC demonstrated shorter chemotherapy durations, poorer overall survival, and increased rates of adverse events despite having similar disease characteristics and treatment patterns. Prospective studies are required to improve outcomes in the elderly population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

52P - Chemotherapy selection in routine clinical practice in Japan for HER2-negative advanced or metastatic breast cancer (KBCRN A001: E-SPEC Study) (ID 534)

Presentation Number
52P
Lecture Time
09:00 - 09:00
Speakers
  • Yookija Kang (Osaka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Anthracycline-based (A) and taxane-based (T) chemotherapy (ChT) are standards of care for triple-negative (TN) or hormone-resistant advanced/metastatic breast cancer (AMBC) in 1st- or 2nd-line ChT. However, the choice of regimen for oncologists and patients is diverse, requiring consideration of not only survival benefit but also quality of life issues. We reported that most patients received eribulin (E) in 1st- or 2nd- line therapy in the Japanese real-world setting at the ESMO 2018 congress. Here, we report updated data regarding ChT sequences and treatment discontinuation.

Methods

We prospectively registered TN AMBC patients and estrogen receptor-positive and HER2-negative AMBC patients who relapsed during or within 6 months after the end of adjuvant endocrine therapy (ET) and were refractory to at least one previous ET. Patterns of ChT and their feasibility were evaluated (ClinicalTrials.gov No. NCT02551263).

Results

Between June 2015 and July 2017, a total of 201 patients were enrolled, 180 of whom were analyzed. The frequent 1st- and 2nd-line ChT sequences were as follows: T followed by E (n=33), oral FU-based therapy (FU) followed by E (n=26), E followed by T (n=21), T followed by FU (n=11), and E followed by FU (n=10). E was administered in 1st- or 2nd-line therapy for 60 patients who did not receive A, and for 35 patients who did not receive T. The main reason the attending physician chose E for patients who did not receive A was “reducing toxicity” in 38.3%, “non-life threatening” in 30.0%, and “patient preference” in 18.3%. Respective ratios in patients who did not receive T were 34.3%, 34.3%, and 20.0%. Patients treated with E or FU in 1st- and 2nd-line ChT had significantly less discontinuation due to adverse events than those with A/T (1st line: p=0.011, 2nd-line: p=0.036). In contrast, there was no statistical difference between E/FU and A/T in 3rd-line ChT (p=1.000).

Conclusions

This study showed that various 1st- and 2nd-sequence treatments including E were chosen in a real-world setting. The lower proportion of adverse events and lower discontinuation rate of E/FU in 1st- and 2nd-line therapy may be due to the better feasibility of these treatments.

Clinical trial identification

NCT02551263.

Legal entity responsible for the study

Kyoto Breast Cancer Research Network.

Funding

Eisai Co., Ltd.

Disclosure

T. Kagimura: Research grant/Funding (self): Eisai. T. Taguchi: Honoraria (self), Donation: Eisai. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

53P - Aromatase inhibitor and cyclin-dependent kinase 4/6 inhibitor treated HR+/HER2- metastatic breast cancer differ to those treated with Aromatase inhibitors alone on progression (ID 870)

Presentation Number
53P
Lecture Time
09:00 - 09:00
Speakers
  • Indunil Weerasena (Perth, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Aromatase inhibitor (AI) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combination is standard first line treatment for HR+/ HER2- metastatic breast cancer (MBC), providing improved progression-free survival (PFS) over AI alone. The combination therapy may delay anti-estrogen resistance including through clonal selection, phenotypic changes and new mutations. We hypothesized that limited progressive disease (LPD) would be more common on combination therapy driven by new mutations at limited site(s), in comparison to more generalized progressive disease (GPD) which would be more common on AI alone due to phenotypic cellular changes across broader sites. Confirmation would indicate that biopsy of progressive sites should be considered for duel-therapy PD and that loco-regional treatment (LRT) options could be explored more frequently for these cases.

Methods

Disease progression (PD) patterns on combined treatment were compared in patients treated in first-line setting for HR+/HER2- MBC. Progressing duel-treated patients (n=16) were compared to historic AI-only treated controls (n=32), matched 1:2 by age and adjuvant therapy. Mode of progression was classified as general (PD in the majority of lesions) or limited (PD in up to two lesions in a single organ). All LPDs were assessed for suitability for LRT at PD.

Results

LPDs were observed in 8 of 16 (50%) patients in the combination group and 4 of 32 (12.5%) in the AI group (p = 0.01). 10 of 12 cases (83%) with LPD were assessed as amenable for LRT. The sites of progression in these ten cases included six in bone, three affecting contralateral breast/chest wall and one in liver. Analysis of time to and mode of second relapse as well as overall survival (OS) for LPDs v GPDs await longer follow-up.

Conclusions

Combined CDK4/6i with AI treated patients in first line HR+/HER- MBC are more likely to develop LPD, where local therapy could be considered with no change to systemic therapy. In contrast general PD was more commonly observed in patients treated with AI alone, warranting change in systemic therapy.

Legal entity responsible for the study

A/Prof. Andrew Redfern, Dr Indunil Weerasena.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

54P - Platinum-based chemotherapy in advanced breast cancer (ABC): Real-world outcome from a tertiary cancer centre in India (ID 990)

Presentation Number
54P
Lecture Time
09:00 - 09:00
Speakers
  • Indhuja Vijesh (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There is a paucity of studies on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India.

Methods

This was a retrospective study of patients with ABC who were treated with platinum-based chemotherapy (gemcitabine carboplatin, GC) in a tertiary cancer center in India from Aug 2015 to Nov 2019. Patients were treated with injection gemcitabine 1gm/m2 on D1/D8 and injection carboplatin (AUC 5-6) on D1 for 6 cycles. Patients were assessed clinically before each cycle and by imaging before 4th and after the 6th cycle. Descriptive statistics were used to analyze the baseline characteristics. Survival was estimated with Kaplan Meier’s curve & univariate/multivariate analysis was done using regression analysis.

Results

Baseline characteristics are listed in the table. 34 % & 91 % had metastatic disease at initial presentation and at the start of GC respectively. Repeat biopsy at metastatic disease was done in 37 % & 50 % had the same molecular subtype. Median number of prior lines of systemic therapy for metastatic/progressive disease was 1 (range: 0 to 5). The median number of sites of metastasis was 2 (range: 0 to 6). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2 to 6). A dose reduction of chemotherapy was done in 74%.Only 57% patients could complete 6 cycles of chemotherapy. The responses among 34 evaluable patients were complete response (11%), partial response (23%), stable disease (40%) and progressive disease (23%). The hematological toxicities of all grade were seen in 91%, and 68% had grade 3 or 4 hematological toxicity. The median progression-free survival (PFS) and overall survival (OS) was 6 months [95% CI: 3.2-5.7 months] and 8 months [95% CI: 5.3-10.7 months] respectively. The 1-year PFS and OS were 19 % and 34% respectively. Univariate analysis did not show molecular subtype & BRCA status as a significant factor in improving PFS.The number of cycles of GC chemotherapy received ( >/= 3 cycles ) and the Infiltrating Ductal carcinoma histology ( IDC ) was significant in improving PFS, ( HR – 2.4, 95 % CI -1.04-5.67, p value – 0.04 ) & ( HR – 3.23, 95 % CI – 1.47 – 7.06, p value -0.03 ) respectively.

Baseline characteristics

Variable n (%)
Age Mean - 45.5 yrs; (28 – 68 yrs)
Sex Female- 34 (97%) Male- 1 (3 %)
Menopausal Status Premenopausal – 26 ( 75 %) Postmenopausal – 8 (23 %)
ECOG PS 1- 29 (83 % ) 2– 6 (17% )
Histology IDC- 27 (77 % ) Mixed – 6 (17% ) Others - 2 (6 % ) *
Grade Grade III -29 ( 83% ) Grade II – 6 (17% )
Hormone Receptor Status Low ER Positive -7 (20 % ) High ER positive- 6 (17% ) ER negative -22 (63 % ) Low PR positive - 5 (14 % ) High PR positive -3 (9 % ) PR negative- 27( 77 % )
Her 2 neu Positive – 6 (17%) Negative –28 (80 % ) Equivocal-1(3 % )
BRCA BRCA 1 – 6 ( 17% ) Negative – 6(17 % ) Not tested – 23 (66% )
Molecular Subtypes Luminal B -13 ( 37% ) Her 2 enriched -3 ( 9 % ) TNBC -19 ( 54% )

* 1 metaplastic, 1 Poorly differentiated with neuroendocrine features

Conclusions

This is the largest study from India on platinum-based chemotherapy in ABC. The real-world outcomes with platinum-based chemotherapy in ABC were PFS 6 months and OS 8 months. On multivariate analysis, patients who completed more than 3 cycles of GC chemotherapy had better survival (p value – 0.003, HR – 3.23, 95 % CI, 1.47 -7.06).

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

55P - Eribulin in heavily pretreated metastatic breast cancer: A real-world data from India (ID 1023)

Presentation Number
55P
Lecture Time
09:00 - 09:00
Speakers
  • Tanmoy K. Mandal (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Treatment of heavily pre-treated metastatic breast cancer (MBC) involves several lines of chemotherapy however, favourable side effect profile and a convenient mode of administration are important. Eribulin, is with proven activity in aggressive MBC however, there is paucity of real-world data from India and merits exploration.

Methods

We retrospectively analyzed, previously treated MBC patients who had at least 2 lines of prior therapy and received intravenous Eribulin at the dose of 1.4 mg/m2 on day 1 and 8 in 3 weekly cycles, between 2013 and 2019. To describe the clinical performance of eribulin we adopted the approach suggested by Dzimitrowicz and colleagues (J Clin Oncol. 2016; 34:3511e17); Tumour Response (TR) was defined as the proportion of physician-reported clinical or imaging (RECIST) response. Furthermore, we evaluated median Progression Free (PFS) and Overall Survival (OS) by the Kaplan Meier method. The patients were monitored for toxicity by CTCAE 4.3 criteria.

Results

There were 78 patients with the median age of 53 (32-75) years, 2 (2.6%) had male breast cancer. The median number of previous chemotherapy lines was 5(2-7); visceral involvement was present in 76 (97.4%) patients with median of 3 organs (range 0-6) involvement and bones (61.5%) being most common site followed by lung (52.5%). A median of 3.5 (1-11) cycles of eribulin was administered. TR seen as partial responses in 35 (44.9%), stable disease in 9 (11.5%), and progressive disease in 34 (43.6%) patients. The median PFS was 3.0 months (95% CI: 2.2-3.8), and median OS was 7 (95% CI: 5.1-8.9) months. Interestingly, eribulin activity was unrelated to the number of previous lines and type of metastatic involvement. Eribulin was well tolerated with only 2 (2.5%) patients discontinuing therapy due to toxicity. Significant grade 3/4 toxicities seen included peripheral neuropathy in 10 (12.8%) which peaked after 6 cycles and neutropenia in 17 (21.8%) of patients while dose reductions were required in 6 (7.7%) of patients.

Conclusions

In this relatively large, single Institution, real practice analysis eribulin is an efficacious, safe and easy to administer option for pre-treated MBC and merits consideration.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

56P - Treatment of palbociclib in hormone receptor-positive breast cancer in China: A real-world study (ID 876)

Presentation Number
56P
Lecture Time
09:00 - 09:00
Speakers
  • Yiqi Yang (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palbociclib has been the first and only CDK4/6 inhibitor approved for breast cancer treatment by China Food and Drug Administration since July 2018. This research concluded the clinical use of palbociclib and provided stratified analyses by indicators that have not been reported, such as weight, percentage of estrogen receptor (ER) plus progesterone receptor (PR), and time to re-biopsy.

Methods

We retrospectively analyzed data from breast cancer patients treated with palbociclib and endocrine therapy from our medical center between May 2018 and January 2020.

Results

Among 51 patients treated with palbociclib, 14 patients were treated in first-line and 37 patients in second or later lines with a median progression-free survival (PFS) of 8 months (95% CI: 5.05-10.96), while the median PFS of first-line patients has not reached. Median PFS of all groups was 10 months (95%CI: 7-13). Patients with recent immunohistochemical confirmation 6 months before had a median PFS of 8 months (95% CI: 5.24-10.79) and group with pathology in 6 months had not reached its mPFS. Non-hepatic metastatic patients had a median PFS of 11 months (95% CI: 9.00-13.00), while the hepatic metastatic ones of 3 months (95% CI: 0.95-5.05). The objective response rate (ORR) was 10.6% (5/47, 95% confidence interval [CI]: 3.5%-23.1%) and clinical benefit rate (CBR) was 67.4% (29/43, 95% CI: 51.5%-80.9%). Better clinical outcomes were associated with recent pathological confirmation of immunohistochemical analysis (P=0.046) and non-hepatic metastasis (P=0.001), but they were not related to ER/PR percentage, Ki67 index, weight, or previous chemotherapy in first/second line of palbociclib setting groups.

Conclusions

Our report indicated favorable efficacy of palbociclib in terms of recent pathological confirmation and non-hepatic metastasis, providing further information about the use of palbociclib.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

57P - Therapeutic vulnerability of malignant phyllodes tumour to pazopanib identified through a novel patient-derived xenograft and cell line model (ID 599)

Presentation Number
57P
Lecture Time
09:00 - 09:00
Speakers
  • Dave Y. Ng (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Phyllodes tumours (PT) are rare fibroepithelial neoplasms accounting for less than 1% of all breast tumours in Western countries and up to 7% amongst Asian populations. Currently, no established standard therapy exists for malignant PT, an aggressive chemoresistant subtype with high metastatic potential. We hypothesized that patient-derived xenograft (PDX) and cell line models created in “real-time” may identify effective therapies to mirror a patient’s treatment trajectory.

Methods

Malignant PT from a chest wall mass was subcutaneously inoculated onto female NSG™ mice with serial transplantation to establish a PDX and cell line model (designated MPT-S1). In vitro cell viability and cell cycle analyses were performed following drug exposures.

Results

The affected patient was diagnosed with metastatic malignant PT affecting the chest wall and lungs. Histology of the chest wall mass showed a high grade malignant tumour composed of markedly pleomorphic spindle cells, interspersed with osteoclast-like multinucleated giant cells. On immunohistochemistry, tumour cells were positive for p63, negative for MNF116 and showed high proliferative index on Ki-67. Whole exome sequencing followed by Sanger sequencing confirmed mutations in TP53, PRB, MED12 and KMT2D. Immunohistochemistry and genomic profiles of the patient’s tumour, PDX, and cell line were consistent. Interestingly, despite primary resistance to conventional chemotherapies including doxorubicin, gemcitabine and docetaxel, the patient achieved partial response to off-label treatment with pazopanib, a multi-targeted receptor tyrosine kinase inhibitor (TKI). Correspondingly, drug susceptibility testing in vitro showed that pazopanib reduced cell viability in a dose-dependent manner (IC50 6.37 μM), accompanied by induction of S-phase arrest and apoptosis. Other TKIs including sorafenib, sunitinib and axitinib elicited similar effects (all IC50 <5 μM).

Conclusions

We established MPT-S1, a new PDX and cell line model of malignant PT, and provided initial evidence for the clinical utility of such models for identifying therapeutic vulnerabilities of rare cancers in real-time.

Legal entity responsible for the study

The authors.

Funding

SingHealth, Duke-NUS.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

58P - Survival benefit of local treatments in breast cancer with lung metastasis: Results from a large retrospective study (ID 971)

Presentation Number
58P
Lecture Time
09:00 - 09:00
Speakers
  • Yimeng Chen (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Systemic therapy is the standard treatment for metastatic breast cancer. However, there has been growing interest in the use of metastasis-directed therapy in selected cases. We investigated the role of local treatments in prolonging survival for lung-only metastases (LM) from breast cancer after mastectomy. Systemic therapy is the standard treatment for metastatic breast cancer. However, there has been growing interest in the use of metastasis-directed therapy in selected cases. We investigated the role of local treatments in prolonging survival for lung-only metastases (LM) from breast cancer after mastectomy.

Methods

Medical records of breast cancer with LM with available clinical data at National Cancer Center in China between 2003 and 2019 were screened. Breast cancer patients with LM receiving local therapy + pharmacotherapy (LPT, n=110) or pharmacotherapy (PT, n=287) were included. Their clinicopathologic characteristics and prognosis were analyzed retrospectively.

Results

After screening a series of medical records of 3785 patients with metastatic breast cancer, 387 were confirmed as initial isolate LM. Patients receiving LPT had significantly longer median overall survival (OS) than those treated with PT: OS 78.9 months versus 53.2 months (P=0.009), respectively. The 3-, 5- and 10-year survival rates for LPT group were 78.3, 58.3 and 25.3%, and those for PT group were 61.8, 42.3 and 20.3% (P = 0.01), respectively. Cox multivariate analysis confirmed the survival benefit induced by LPT. Estrogen receptor (ER)-negative of the primary tumour, ki67>20%, disease-free interval from surgery to LM≤24 months, LM-associated symptoms, and patients receiving systemic pharmacotherapy only were independently associated with poor prognosis.

Conclusions

Adding local therapy to systemic pharmacotherapy might prolong survival for lung metastases in breast cancer. Well-designed randomised clinical trials are warranted in the future.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

59P - The impact of site of metastasis on overall survival in indigenous and non-indigenous patients of Western Australia with breast cancer (ID 997)

Presentation Number
59P
Lecture Time
09:00 - 09:00
Speakers
  • Azim Khan (Nedlands, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Indigenous women with breast cancer (BrCa) have markedly higher mortality then non-Indigenous women. Here, we examine the impact of site of metastasis on overall survival (OS) in women with breast cancer by indigenous status.

Methods

We retrospectively examined data from WA cancer registry from 2001 to 2016 with metastatic BrCa by indigenous status. Cases with confirmed location of metastatic disease were analysed and divided into groups of bone, liver, brain, lung, gastrointestinal (GI)/genitourinary (GU), contralateral breast (CBr) and skin metastasis. We performed a univariate and linear regression analysis to determine the impact of metastasis site on OS. Kaplan-Meier, Chi-square, Mann-Whitney analysis were done.

Results

A total of 152 patients were studied, 39% (n=60) were indigenous vs 61% (n=92) non-indigenous. Inferior median OS for indigenous group 34 vs 51 months in non-indigenous group, p=0.015. Indigenous group had higher rates of metastasis to bone 61% vs 40% (p=0.014), lung 41% v 25% (p=0.031), liver 41% v 23% (p=0.021) when compared to non-indigenous patients. The GI/GU metastasis was higher in non-indigenous group 32% v 15% (p=0.015) in indigenous group. There were no significant differences in rate of relapse at the local, CBr, brain, spleen, non-axillary LN nor skin (p>0.05). The bone metastasis was most common in luminals, liver and lung metastasis were frequent in luminal B and Her2+ subtypes. Brain metastasis was most frequent in HER2+. Indigenous cohort had more HER2+, luminal B and TN’s than non-indigenous but this was non-significant, p < 0.467. The multiple linear regression in both groups to predict OS for site-specific metastasis was non-significant with p-value 0.067 and R2 of 0.097, explaining slight variability of OS by sites of metastasis. After adjustment, only brain metastasis had significant regression weights, but further analysis shown non-significant effect on OS with p=0.072 and an R2 of 0.021.The group with brain metastasis had OS of 38 vs 52 months with no brain metastasis, p=0.072.

Conclusions

The indigenous group had inferior survival and higher rates of relapse to bones and viscera. A larger prospective study is needed to establish links of site of metastasis and OS.

Legal entity responsible for the study

Dr Azim Khan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

60P - Risk factors of bone metastasis and skeletal-related events in high-risk breast cancer patients (ID 407)

Presentation Number
60P
Lecture Time
09:00 - 09:00
Speakers
  • Sumadi Lukman Anwar (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The bone is the most common site of distant metastasis from breast cancer that predisposes the patients for skeletal-related events (SREs) and often causes severe morbidity and poor quality of life. Identification of predilections and risk factors associated with bone metastasis and SREs is important in planning (neo)adjuvant treatment and surveillance systems particularly in a population of patients diagnosed in late stages such as in Indonesia and other developing countries.

Methods

Clinicopathological variables of breast cancer with intermediate to the high-high risk of recurrence were collected from a dataset in the Dr Sardjito Hospital, Indonesia. Risk factors affecting bone metastasis and SRE were then analyzed.

Results

Of 1081 non-metastatic breast cancer patients diagnosed from 2013 through 2018, 129 patients (11.9%) developed bone metastasis during a median follow up of 4.4 years. SREs occurred in 89 (68.5%) patients. In multivariable analysis, positive axillary lymph nodes (OR 2.189, p=0.002), early menopause (OR 2.020, p=0.030), luminal subtype (OR 1.811, p=0.003), advanced stage (OR 1.869, p=0.004), and having multiple metabolic comorbidities (OR 1.992, p=0.004) were significantly associated with risk of skeletal metastasis. Only positive lymph nodes, luminal subtype, and advanced stages were associated with higher SREs. Of 102 (82.2%) and 52 (40.3%) patients received bone-modifying agents and external radiotherapy, respectively.

Conclusions

The rates of bone metastasis and SREs are relatively high in breast cancer patients diagnosed in advanced stages. Our study suggests the importance of considering patients with high-risk of SREs and the need of treatment advancement to further prevent SREs in the care of breast cancer with bone metastasis.

Legal entity responsible for the study

Sumadi Lukman Anwar.

Funding

Universitas Gadjah Mada.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

61P - Clinical implication of BRCA mutation in breast cancer with central nervous system metastasis (ID 525)

Presentation Number
61P
Lecture Time
09:00 - 09:00
Speakers
  • Jwa Hoon Kim (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Clinical implication of BRCA mutation in patients with breast cancer (BC) with central nervous system (CNS) metastasis is unclear.

Methods

Data of 2,883 patients with BC who underwent BRCA1/2 mutation test at Asan Medical Center between 2011 and 2018 were reviewed. Clinical characteristics and outcomes were compared according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis.

Results

Among 2,883 patients, 82 patients developed CNS metastasis: 29 of 696 (4.2%) in BRCA1/2 mutation carriers and 53 of 2,187 (2.4%) in non-BRCA mutation carriers. Median age at CNS metastasis was 41 yrs (range 27-76). The proportion of BC subtypes was different according to the presence of BRCA1/2 mutation: hormone receptor (HR) (+) and HER2 (-) (41.4% vs. 24.5%, P=0.113) and HER2 (+) regardless of HR (6.9% vs. 32.1%, P=0.013) between BRCA1/2 mutation and non-BRCA mutation carriers, while no difference was observed regarding triple-negative BC (TNBC) (51.7% vs. 43.4%) (P=0.470). Among patients with BRCA1/2 mutation, most of the BRCA1 mutation carriers had TNBC (77.8%), whereas most of BRCA2 mutation carriers had HR+ BC (60%) (P=0.060). Median time to CNS metastasis from metastatic BC was 1.1 yrs (95% confidence interval 0.74-1.41) without difference between BRCA1/2 and non-BRCA mutation carriers. BRCA1 carriers significantly develop CNS metastasis earlier than BRCA2 mutation carriers (0.8 vs. 1.6 yrs, P=0.015). Patterns of CNS metastasis were similar by presence of BRCA1/2 mutation: brain parenchymal metastasis (BM) alone (62.1% vs. 73.6%), leptomeningeal metastasis alone (10.3% vs. 9.4%), and both (27.6% vs. 17%). There were no differences in isolated CNS metastasis, single or multiple BM, and uncontrolled CNS metastasis rates with similar treatment of CNS metastasis. At a median follow-up of 24.5 months, median overall survival from CNS metastasis in BRCA1/2 mutation carriers seemed to be shorter than in non-BRCA mutation carriers (6.0 vs. 8.9 months, P=0.284).

Conclusions

CNS involvement is frequent in BRCA1/2 mutated BC and BC subtypes were different according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis. BRCA1 carriers developed CNS metastasis earlier and may be associated with poor survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

62P - IGF axis in breast cancer recurrence and metastasis (ID 1014)

Presentation Number
62P
Lecture Time
09:00 - 09:00
Speakers
  • Hajara Akhter (Dhaka, Bangladesh)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) are the major components in the IGF axis that play an important role in the development and progression of cancer. However, little is known about the circulatory levels of these proteins with recurrence and metastasis in breast carcinoma (BC).

Methods

One hundred and twenty-eight (128) breast cancer patients who underwent mastectomy were purposively taken from a prospective study. Clinicopathological information was collected from patients’ medical records. Anthropometric and biochemical parameters were measured by standard methods. Growth and metabolic factors were estimated by enzyme-linked immunosorbent assay (ELISA), and compared for patients’ recurrence and metastasis.

Results

The mean age at diagnosis was 44 years. Most of the tumors (94%) were ductal cell carcinoma. Two thirds were moderately differentiated tumor grade and lymph node positive [70% and 67% respectively]. Circulatory levels of IGFBP1 were significantly higher (p<0.05) in patients who received adjuvant chemotherapy; and patients with recurrence and metastasis while IGF1 was found to be significantly increased in only metastatic breast cancer (p<0.05). IGFBP-1 levels were correlated with SGPT, ALP, hemoglobin, WBC, ESR, CA15.3 and contraceptive use, whereas, IGF-1 was associated with insulin, HOMA %B and ESR.

Conclusions

High serum levels of IGFBP-1 and IGF-1 may be associated with breast cancer recurrence and metastasis. These results need to be confirmed in larger breast cancer survivor cohorts.

Legal entity responsible for the study

TWAS, Ministry of Education (MoE) Bangladesh.

Funding

The World Academy of Sciences (TWAS), Trieste, Italy. Bangladesh Bureau of Educational Information & Statistics (BANBEIS), Ministry of Education (MoE), Dhaka, Bangladesh.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

63P - Butterfly pea (Clitoria ternatea Linn.) flower extract prevents MCF-7 HER2-positive breast cancer cell metastasis in-vitro (ID 676)

Presentation Number
63P
Lecture Time
09:00 - 09:00
Speakers
  • Azzahra -. Asysyifa (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is one of the cancers with highest incidence with more than two million people diagnosed in 2018 and causes more than 600.000 deaths. The big number of deaths are mostly due to breast cancer metastasis. Butterfly pea flower (Clitoria ternatea Linn.) is a medicinal plant which is known to have a wide range of pharmacological activities because it contains many kinds of active substances one of which is quercetin known to have anti-breast cancer activity especially metastasis through inhibition of NF-κB (nuclear factor kappa B). Those transcription factors play an important role in the metastasis process in HER2-positive breast cancer type. The butterfly pea flower activity as an antimetastatic agent in MCF-7 HER2-positive has not been well understood. The aim of the study was to find out the antimetastatic activity of butterfly pea flower extract on MCF-7 HER-positive breast cancer cell line.

Methods

Maceration process using 96% ethanol to obtain the crude extract, thin layer chromatography (TLC) to see the phytochemical profile of butterfly pea leaf extract, MTT assay to determine the IC50 using log probit analysis as a reference for the next test which is scratch wound healing assay to assess the effect of butterfly pea leaf extract on the migration of 4T1 breast cancer cell line.

Results

Butterfly pea flower extraction using maceration obtains a 18.06% yield. Phytochemical study using thin layer chromatography suggested the Rf of crude extract had the same Rf with quercetin standard which is 0.57 so it was proven that the crude extract contained quercetin. The MTT assay and log probit analysis showed the IC50 of butterfly pea crude extract was 862 μg/mL. The scratch wound healing assay using concentrations below IC50 showed 50% of cell migration activity of the MCF-7 HER2-positive was inhibited in 24 hours interval by 380 μg/mL crude extract and in 48 hours interval with 500 μg/mL of crude extract was able to prevent the scratch closure. Statistical analysis using SPSS 16.0 showed that the crude extract can significantly suppressed the migration of the cancer cell.

Conclusions

Butterfly pea flower extract has an antimetastatic activity to MCF-7 HER2-positive breast cancer cell line in-vitro.

Legal entity responsible for the study

The authors.

Funding

UGM.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

64P - Pre-treatment absolute white blood cell profile count as metastatic predictive factors in invasive ductal carcinoma breast cancer (ID 815)

Presentation Number
64P
Lecture Time
09:00 - 09:00
Speakers
  • Wikania W. I Gede (Denpasar, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Metastasis is the one main causes of mortality in solid cancers, including breast cancer recently predictive biomarkers based on molecular finding have been developed but still unaffordable especially in developing countries. There are several alternative to molecular biomarkers and white blood cell profile count emerged as affordable and practical markers of cancer progression. However, there are not many studies that focus on their direct application. Therefore, this study aimed to determine the correlation between white blood cell profile count as predictive factors of metastasis in invasive ductal carcinoma breast cancer.

Methods

A retrospective cross-sectional study was conducted using breast cancer patient data obtained at Sanglah General Hospital (2016-2020). Complete blood count (CBC) and histopathological records of the patients were collected and the white blood cell profile (WBC, ABC, AMC, AEC, ANC and ALC) were calculated. Distant metastasis was classified into M0 and M1.

Results

267 invasive ductal carcinoma breast cancer patient data were used in this study with mean age 49.1 ± 9.474. Metastatic disease of the patients accounted for 50 patients (18.7%) of all patients. Patients with metastatic disease had higher median of AMC compared to patients without metastasis (0.61 ± 0.307, p=0.022. The AUC (sensitivity and specificity) of ABC, AMC and ANC in predicting metastasis were 0.528 (24%; 90%), 0.604 (56%; 72%) and 0.539 (40%; 74%), respectively. In univariate risk analysis model, patient with metastasis of invasive ductal carcinoma breast cancer was found in high ABC (OR: 2.779; 95%CI=1.277-6.134; p=0.008), AMC (OR: 1.203; 95%CI=0.661-2.189; p<0.001) and ANC (OR: 1.917; 95%CI=1.008-3.643; p=0.045).

Conclusions

Pre-treatment white blood cell profile count are potential predictive markers for metastasis. However, these findings need to be validated in larger study with more comprehensive design.

Legal entity responsible for the study

Medical Faculty Udayana University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

65P - The new mouse anti-nNav1.5 monoclonal antibody (ID 954)

Presentation Number
65P
Lecture Time
09:00 - 09:00
Speakers
  • Nur Aishah Sharudin (Kubang Kerian, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neonatal Nav1.5 (nNav1.5) is a potent tumour metastatic marker found re-expressed in human breast cancer cells with aggressive phenotype and breast tumour tissue positive for lymph node metastasis. Mouse anti-nNav1.5 monoclonal antibody, 4H8 was recently obtained.Neonatal Nav1.5 (nNav1.5) is a potent tumour metastatic marker found re-expressed in human breast cancer cells with aggressive phenotype and breast tumour tissue positive for lymph node metastasis. Mouse anti-nNav1.5 monoclonal antibody, 4H8 was recently obtained. This study aimed to assess the specificity of the 4H8 against nNav1.5.

Methods

4H8 was used as primary antibody in Western blot and immunocytochemistry tested on cells and cell lysates, respectively of two human breast cancer cell line; MDA-MB-231+nNav1.5 and MCF-7-nNav1.5, a mouse mammary cancer cell line, 4T1+nNav1.5, a non-cancerous human breast epithelial, MCF-10A-nNav1.5 and tumour tissue lysate from an orthotopic syngeneic mouse model (4T1+nNav1.5/BALB/c).

Results

were consistent with nNav1.5 protein being more abundantly expressed in aggressive human breast cancer cell line, MDA-MB-231+nNav1.5 and mouse mammary cancer cell line, 4T1+nNav1.5 and tumour tissue lysate from an orthotopic syngeneic mouse model (4T1+nNav1.5/BALB/c) as compared to MCF-7-nNav1.5 and MCF-10A-nNav1.5.

Conclusions

The new antibody described in this work can be a novel tool in studying nNav1.5 expression in breast cancer.

Legal entity responsible for the study

Institute of Research for Molecular Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

66P - The TILs near solid structures is a potential prognostic factor of distant metastases in the luminal HER2-negative breast cancer (ID 973)

Presentation Number
66P
Lecture Time
09:00 - 09:00
Speakers
  • Vladimir V. Alifanov (Tomsk, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The phenomenon of intratumoral morphological heterogeneity is associated with both the progression of the disease and chemosensitivity and chemoresistance. However, there are very few data about the microenvironment heterogeneity near morphological structures in breast cancer patients of various molecular subtypes. This phenomenon may underlie the failure of tumor-infiltration lymphocytes as a prognostic factor in luminal forms of breast cancer.

Methods

152 patients with IC NST (T1–3N0–2M0) aged 29 to 75 years were enrolled in the study. The molecular subtype was determined using immunohistochemical analysis of the expression of estrogen and progesterone receptors, Ki-67 and Her2/neu. TILs were assessed in accordance with the recommendations of the International TILs Working Group

Results

It was shown that TILs near the various morphological structures is heterogeneous only in luminal Her2-negative patients. In addition, was found that the development of distant metastases and worse metastatic-free survival in this cohort of patients is associated with a high (more than 5%) TILs near solid structures and also depended on Ki-67 level.

Conclusions

TILs near solid structures is a potential prognostic factor for the development of distant metastasis in the luminal Her2-negative and Ki-67 level less 20% subtype of IC NST. The study was supported by the Russian Science Foundation (grant #20-75-10033).

Legal entity responsible for the study

The authors.

Funding

the Russian Science Foundation.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

67TiP - HER2CLIMB-02: A randomized, double-blind, phase III study of tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer (ID 283)

Presentation Number
67TiP
Lecture Time
09:00 - 09:00
Speakers
  • Norikazu Masuda (Osaka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US for use in combination with trastuzumab (Tras) and capecitabine for treatment (tx) of patients (pts) with metastatic HER2+ breast cancer (MBC), including pts with brain metastases (BM), who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for tx of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Improvements are needed, including pts with active BM. A phase Ib trial evaluated TUC (300 mg PO BID) with T-DM1 in 50 pts with HER2+ MBC who received prior tx with Tras and a taxane; 60% of pts had BM at baseline (Borges 2018). Common AEs, mostly grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in pts with measurable disease (n=34) was 47%. Brain specific response rate (RECISTv1.1) in pts with measurable BM (n=14) was 36%. This encouraging clinical activity, including in pts with BM, provides rationale to evaluate this combination.

Trial design

HER2CLIMB-02 is a global, randomized, double-blind, placebo-controlled, phase III study enrolling pts with centrally confirmed HER2+, unresectable, locally advanced, or MBC previously treated with Tras and taxane (in any setting), and ECOG ≤1. ∼460 pts will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior tx with investigational anti-HER2 or anti-EGFR agent or HER2 TKI is not permitted. Prior pertuzumab tx is permitted. Baseline brain MRIs are required; pts with stable, progressing, or untreated BM not requiring immediate local therapy are eligible. On tx response assessments per RECISTv1.1 occur every 6 wks for the 1st 24 wks, and then every 9 wks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in North America, EU, and will include Japan, South Korea, Singapore, and Australia.

Clinical trial identification

NCT03975647; 2019-005017-39.

Legal entity responsible for the study

Seattle Genetics, Inc.

Funding

Seattle Genetics, Inc.

Disclosure

N. Masuda: Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli-Lilly; Honoraria (self): Takeda; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Daiichi Sankyo; Full/Part-time employment: National Hospital Organization Osaka National Hospital, Dept. of Surgery, Breast Oncology; Officer/Board of Directors: Japan Breast Cancer Research Group Association Board of Directors. S. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): OBI Pharma; Advisory/Consultancy, Research grant/Funding (institution), medical writing: Pfizer; Research grant/Funding (institution): Pieris Pharma; Research grant/Funding (institution): Puma Biotech; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, medical writing: Roche; Research grant/Funding (institution): Bayer. L. Vahdat: Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Berg Pharma; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Other: Roche; Research grant/Funding (institution), Other: Arvinas; Research grant/Funding (institution): Polyphor; Research grant/Funding (institution): Oncotherapy Biosciences; Licensing/Royalties, A patent on bone marrow derived progenitor and relapse: No company. N. Harbeck: Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Officer/Board of Directors: West German Study Group. A.C. Wolff: Full/Part-time employment: John Hopkins Kimmel Cancer Center, Breast and Ovarian Cancer Program. S.M. Tolaney: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celldex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nanostring; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Paxman; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Odonate; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Anthenex; Honoraria (self), Advisory/Consultancy: Oncopep; Honoraria (self), Advisory/Consultancy: Kyowa Kirin Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Exelixis. S. Loi: Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Novartis; Advisory/Consultancy: GlaxosmithKline; Advisory/Consultancy: G1 Therapeutics; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Bristol-Meyers Squibb; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Merck; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Roche-Genentech; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Pfizer; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. J. O'Shaughnessy: Honoraria (self): AbbVie; Honoraria (self): Agendia; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi-Sankyo; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Grail; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ispen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Jounce; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Myriad; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Odonate Therapeutics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Samsung; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics, Inc.; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Syndax; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi. D. Xie: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics, Inc.; Shareholder/Stockholder/Stock options: Metlife. L. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Seattle Genetics, Inc.. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics, Inc.. V.F. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Research grant/Funding (self): Abbot/AbbVie; Research grant/Funding (institution): Millenium.

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e-Poster Display Session (ID 87) Poster Display

68TiP - KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (ID 515)

Presentation Number
68TiP
Lecture Time
09:00 - 09:00
Speakers
  • Shigehira Saji (Fukushima, Fukushima, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immunotherapy + chemotherapy (chemo) is a promising approach for 1L treatment of locally recurrent, inoperable TNBC or metastatic TNBC (mTNBC). An unmet need exists for effective and tolerable maintenance regimens in mTNBC to sustain clinical benefit after induction therapy and avoid potential toxicity or resistance to prolonged chemo. The PARP inhibitor ola has shown efficacy as maintenance therapy for platinum-sensitive ovarian cancer. The high prevalence of BRCAm (or “BRCAness”) in TNBC may make these tumors sensitive to DNA-damaging agents. Moreover, evidence suggests that ola + PD-1 inhibitor pembro may provide greater clinical benefit than with either agent alone. KEYLYNK-009 (NCT04191135) is a phase II/III, open-label, randomized study of pembro + ola vs chemo after induction with 1L pembro + chemo in locally recurrent, inoperable TNBC or mTNBC.

Trial design

This 2-in-1 study will enroll ∼317 pts in phase II and ∼615 additional pts in phase III if a planned efficacy boundary is met. Pts eligible for induction therapy must have measurable, locally recurrent, inoperable TNBC that cannot be treated with curative intent or mTNBC previously untreated with chemo. Pts will receive up to 6 cycles of induction therapy with pembro 200 mg Q3W + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 + 8 Q3W). Pts eligible for postinduction treatment must achieve CR or PR or maintain SD during induction after 4-6 treatment cycles, with ECOG PS 0/1 and no persistent grade >1 toxicities related to induction therapy (excluding alopecia, Hb ≥9.0 g/dL, grade 2 hyper-/hypothyroidism, or grade 2 hyperglycemia). These pts will be randomized 1:1 to pembro 200 mg Q3W + ola 300 mg BID or continue pembro + chemo (same as induction regimen) until completion of 35 cycles of pembro (including induction), progression, or unacceptable toxicity. Phase III primary endpoints are PFS (RECIST v1.1 by BICR) and OS. Secondary endpoints include OS and PFS in pts with BRCAm, HRQoL, and safety. Pt enrollment is ongoing and anticipated at 110 sites in 14 countries.

Clinical trial identification

NCT04191135.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

S. Saji: Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self): Daiichi Sankyo; Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self): Eli Lilly; Honoraria (self): Kyowa Kirin; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self): Takeda. A. Llombart Cussac: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties: MedSIR. F. Andre: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: GlaxoSmithKline. M.E. Robson: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca.; Advisory/Consultancy: Change Health Care; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): InVitae; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Non-remunerated activity/ies, Physician Education Resource; Research to Practice: Clinical Care Options; Non-remunerated activity/ies, Uncompensated Relationships: Daiichi Sankyo; Non-remunerated activity/ies, Uncompensated Relationships: Merck; Non-remunerated activity/ies, Uncompensated Relationships: Pfizer. N. Harbeck: Shareholder/Stockholder/Stock options: West German Study Group; Honoraria (self): Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Genomic Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self): Zodiac Pharma; Advisory/Consultancy: Agendia; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: West German Study Group. P. Schmid: Research grant/Funding (institution), Full/Part-time employment: Genentech; Honoraria (self), Research grant/Funding (institution), Full/Part-time employment: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Honoraria (self): Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Puma Biotechnology; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Oncogenex. D.W. Cescon: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Agendia; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Licensing/Royalties, Patent Pending: Biomarkers of TTK inhibitors : University of Toronto. J.S. Ahn: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb-Ono Pharmaceutical; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Menarini; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Roche; Advisory/Consultancy: Samsung Bioepis. R. Nanda: Advisory/Consultancy: Aduro; Advisory/Consultancy: Athenex; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Ionis; Advisory/Consultancy: Macrogenics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Corcept Therapeutics; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Odonate Therapeutics; Non-remunerated activity/ies: G1 Therapeutics. L. Fan: Full/Part-time employment: li_fan2@merck.com. J.A. Mejia: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. V. Karantza: Shareholder/Stockholder/Stock options, Full/Part-time employment: erck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A. Bardia: Advisory/Consultancy: Biotheranostics Inc.; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy: Diiachi Pharma/AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho. H.S. Rugo: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): OBI; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Odonate; Advisory/Consultancy: Puma; Advisory/Consultancy: Samsung.

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e-Poster Display Session (ID 87) Poster Display

69TiP - MADELINE Asia: A mobile app-based prospective observational study of patient reported outcomes in advanced breast cancer in Asia (ID 757)

Presentation Number
69TiP
Lecture Time
09:00 - 09:00
Speakers
  • Anna Y. Tai (Hong Kong, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The incidence of breast cancer in Asia is rising. Recent advances in hormone receptor (HR) positive and human epidermal growth factor receptor negative advanced breast cancer (aBC) includes introduction of the CDK 4/6 inhibitors. Palbociclib was the first drug in this class to be introduced in Asia and is approved for use in aBC in combination with aromatase inhibitors (P+AI) as initial endocrine based therapy in postmenopausal women or with fulvestrant (P+F) in women with disease progression following endocrine therapy. Globally, there has been evaluations in the real world setting for palbociclib. However, data published for Asian patients in this setting remains scarce.

Trial design

Study Design: A prospective, observational, non-interventional, multi-centre study. A smartphone-based mobile application to collect patient-reported outcomes (PROs) associated with aBC and its treatment on Palbociclib has been developed. The impact of aBC and associated treatment of symptoms, functioning and quality of life (QOL) as reported by patients will be studied. Clinical data on therapy management, occurrence of neutropenia and any association between neutropenia, quality of life and PROs will also be captured. Eligibility Criteria: Women with HR+/HER2– aBC receiving P+AI or P+F as per approved indication in their country. Aims and Objectives: Primary objectives are to assess and describe clinical and PROs in eligible patient population. 12-Item ‘Short Form Health Survey’ & ‘Center for Epidemiological Studies Depression Scale’ would be used. The study will also document changes in therapy as well as the incidence, severity, and duration of neutropenia through data recorded from patient’s medical records. Statistical Methods: For the purpose of this study, analyses will generally be descriptive in nature and will be conducted using SAS statistical software Present Accrual and Target Accrual: Approximately 100 patients from up to 12 sites within 4 Asian countries (Taiwan, India, Malaysia and Hong Kong) will be enrolled. Study duration will be approximately 12 months assuming 6 months of recruitment. The study is open in all 4 participating countries with 7 patients recruited so far.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

M. Singh, J. Binko, M. Alam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. K. Lilly, S. Chang: Full/Part-time employment: Parexel International Pty Ltd. S. Bowles: Full/Part-time employment: Intouch Solutions. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO5 - Response of an ERBB2 Exon 20 Insertion Mutation Breast Cancer to Pyrotinib (ID 1015)

Presentation Number
YO5
Lecture Time
09:00 - 09:00
Speakers
  • Fan Yang (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

Developmental therapeutics (ID 1144)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

73P - Selinexor in combination with carboplatin and pemetrexed (CP) in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multi-arm phase Ib study (ID 278)

Presentation Number
73P
Lecture Time
09:00 - 09:00
Speakers
  • Kyaw Z. Thein (Portland, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Exportin 1(XPO-1) is overexpressed in various tumors and selinexor is a first-in-class oral potent selective inhibitor of XPO-1, leading to intranuclear accumulation of tumor suppressor proteins. In vivo studies have suggested that selinexor in combination with various chemotherapeutics exerts antitumor activity in multiple cancers.

Methods

This was an open label, single-center, multi-arm phase Ib study utilizing a “3 + 3” design and a “basket type” expansion. CP + selinexor was employed as one of the 13 parallel arms. While carboplatin was dosed at AUC6 along with pemetrexed at 500 mg/m2 IV Q3W, selinexor was dosed at 60 mg twice weekly (BIW) or 40-60 mg once weekly (QW). Patients with advanced or metastatic solid tumors whose disease was refractory, had relapsed following prior systemic therapy or where the addition of selinexor to standard chemotherapy deemed appropriate and acceptable, were eligible.

Results

Six patients with the median age of 51 (range, 37–69 years) were treated, and 4 were evaluable for response. The cancer types were ovarian (n=2), and 1 each with thymoma, cervical, rectal, and non-small cell lung cancers. All patients had at least one treatment-emergent adverse events (TEAE) and the common TEAE were thrombocytopenia (6/6), neutropenia (5/6), fatigue (5/6), anemia (4/6), leukopenia (4/6), elevated AST or ALT (3/6), nausea (3/6), and vomiting (3/6). The most prevalent grade ≥3 TEAE were thrombocytopenia (4/6), anemia (3/6), neutropenia (3/6), leukopenia (2/6), and fatigue (2/6). A patient dosed at selinexor 40mg QW experienced DLT with grade 3 fatigue despite medical supportive care ≥5 days. The patient with lung adenocarcinoma who had 2 prior therapies including prior carbo-taxol achieved partial response (PR) whereas 2 patients with ovarian cancer and cervical cancer had stable disease (SD), contributing the clinical benefit rate (CR+PR+SD ≥4 months) of 50%.

Conclusions

Albeit the number of patients in this study arm was small, once weekly oral selinexor in combination with CP was plausible and conferred some clinical activity and disease stabilization. The RP2D of selinexor was 40 mg QW in combination with CP.

Clinical trial identification

NCT02419495.

Legal entity responsible for the study

The authors.

Funding

Karyopharm.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

74P - Comprehensive transcriptome analysis of endoplasmic reticulum stress in osteosarcomas (ID 932)

Presentation Number
74P
Lecture Time
09:00 - 09:00
Speakers
  • Yoshiyuki Suehara (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bone and soft-tissue sarcomas are rare malignant tumors comprising numerous histological subtypes. Novel effective therapies are still required. Recently, endoplasmic reticulum stress (ERs) responses have been suggested to be involved in the malignancy of various cancer types, prompting new studies focused on this area for the development of new therapies. Our previous proteomic study demonstrated an association between the ERs response and malignant behaviors in Ewing sarcomas (ESs). We also found that IRE1α inhibitors exert antitumor activity in ESs (Tanabe Y et al. Oncotarget 2017). To develop novel therapies for osteosarcomas (OSs), we performed comprehensive expression study of ERs genes using ER response arrays. Identified factors based on ER response arrays were investigated to elucidate these functional and antitumor activities using inhibitors of identified ERs in OSs.

Methods

To elucidate roles of main ER pathway in OS, we performed ER response arrays using OS cell lines. Based on results of ER response arrays, we conducted reverse transcription polymerase chain reaction (RT-PCR) and quantitative (q)-PCR to elucidate the expression of XBP1 and XBP1 splicing (XBP1s) variants in OS cell lines (143B, MG63, KHOS, KHOSR2, U2OS, U2OSR2) and surgical materials. Furthermore, we also performed XBP1 siRNA and inhibitor assays using several IRE1α-XBP1 inhibitors.

Results

ER response arrays using OS cell lines indicated some other pathways including XBP1 had high expressions in transcriptome levels. As we suggested XBP1played crucial roles in OS cell lines, we conducted functional assay focusing on XBP1 in OS cell lines. Expression of XBP1 was confirmed in OS cell lines and surgical materials by RT-PCR. The knockdown of XBP1 expression by siRNA inhibited the cell proliferation of the OS cell lines. Regarding inhibitor assays using IRE1α-XBP1 inhibitors, toyocamycin exerted a strong anti-tumor effect (IC50 <0.07 [0.04 to 0.07] μM) in the OS cell lines, despite SYO1, synovial sarcoma cell line had resistance of the inhibitor.

Conclusions

We found the association between the ER response and the tumor activity in OS. We also found that IRE1α-XBP1 inhibitors suppressed cell growths in OS.

Editorial acknowledgement

This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19H03789 and 19K22694 to Y.S.; 19K16753 to K.A.; 18K15329 to T.O.; # 18K16634 to Y.K.).

Legal entity responsible for the study

The authors.

Funding

This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19H03789 and 19K22694 to Y.S.; 19K16753 to K.A.; 18K15329 to T.O.; # 18K16634 to Y.K.).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

75P - The evaluation of selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer (ID 401)

Presentation Number
75P
Lecture Time
09:00 - 09:00
Speakers
  • Leo Yamada (Fukushima, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene and frequently mutated in gastric cancer (GC). Although ARID1A mutations are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach are effective for ARID1A-deficient cancers. EZH2, the histone methyltransferase and a member of the polycomb repressive complex 2 (PRC2), catalyzes the trimethylation of lysine 27 on histone 3 and showed a synthetic lethality in ARID1A-mutated ovarian cancer, but its role in GC has not been investigated yet.

Methods

The selective sensitivity of the EZH2 inhibitors for ARID1A-deficient GC cells was evaluated using cell viability and colony formation assays enrolling three kinds of EZH2 inhibitors. The expression of PI3K/AKT signaling genes was investigated using TCGA’s cBioPortal database to determine whether the homeostasis between ARID1A and EZH2 is related to cell proliferation and survival via the PI3K/AKT signaling pathway. We also evaluated the expression of EZH2, PD-L1, and PD-L2, MSI status, and EBV infection were investigated in ARID1A negative GC using patient samples.

Results

EZH2 inhibitors decreased the viability of ARID1A-deficient cells in a dose-dependent manner and demonstrated the selective sensitivity to ARID1A-deficient cells in vitro experiment system. A bioinformatics approach revealed that the PI3K/AKT signaling tended to be activated in ARID1A-deficient GC enhancing cell viability and, furthermore, down-regulation of EZH2 in ARID1A-deficient GC was related to normalization of PI3K/AKT signaling pathway. Clinicopathological characteristics of ARID1A negative GC with ARID1A, EZH2, PD-L1, and PD-L2 expressions, MSI, and EBV status were summarized.

Conclusions

The present findings provide a rationale for the selective sensitivity of EZH2 inhibitors against ARID1A-deficient GC and suggest the potential efficacy of targeted therapy using EZH2 inhibitors in this patient population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

76P - Targeted tumour photoImmunotherapy against triple-negative breast cancer therapy (ID 154)

Presentation Number
76P
Lecture Time
09:00 - 09:00
Speakers
  • Vivek Raju (Coimbatore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have an approved targeted therapy. Therefore, patients primarily depend on forceful treatment of systemic chemotherapy that has inevitable adverse effects, shows poor therapeutic outcomes, leads to high mortality rates, and advanced stage of TNBC patients remains very high. Hence, there is a need to develop effective targeted therapies for the TNBC patient population. Emphasizing the new nanotherapeutic approach in TNBC for combinational therapy could be an effective strategy.

Methods

Herein, we used the electrostatic assembly method to develop smart therapeutics with targeting ligand of hyaluronan (HA) for tumor photothermal treatment. Furthermore, we calculate the photothermal property and photothermal conversion efficiency under prominent irradiation. Then, we co-encapsulated the immuno molecues for to trigger immunne responses against the tumors. In vivo analysis of photoimmunotherapy efficacy of targeted therapy in mice models was done.

Results

Encouragingly, therapeutics have selective receptor-targeted specific endocytic uptake of TNBC and incinerates the tumor under irridiation releasing tumor-associated antigens. Furthermore, co-encapsulated imiquimod (R837) immunoadjuvant molecules trigger strong immune response against post-phototherapy of tumor. Therefore, nanotherapeutics based photoimmunotherapy is an effective combined treatment for TNBC to protect the mice from cancer relapse and metastasis.

Conclusions

We conclude that results of smart therapeutics platform could serve as a new photoimmunotherapy modality for future clinical use. Combined cancer immunotherapy has the greatest potential for the treatment of cancer and prevention of future relapse by the activation of the immune system to recognize and kill tumor cells.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

77P - Dual targeting oxidative phosphorylation and glycolysis in triple-negative breast cancers: En route to effective inhibition of tumour metabolism (ID 470)

Presentation Number
77P
Lecture Time
09:00 - 09:00
Speakers
  • Alexander M. Scherbakov (Moscow, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-negative breast cancer is a highly aggressive type of breast tumors characterized by the lack of targets for hormone and anti-HER2 therapy. Inhibition of tumor metabolism is one of the promising approaches in the treatment of triple-negative breast cancer. As shown by previous studies, single treatments with oxidative phosphorylation (OxPhos) or glycolysis inhibitors were ineffective. The work aimed to develop novel oligomycin derivatives (OxPhos inhibitors) and evaluate their activity in combination with glycolysis inhibitors, 2-deoxyglucose (2DOG) and 3-bromopyruvate (3BP).

Methods

MCF-7 and MDA-MB-231 breast cancer cell lines and MCF-10A human mammary epithelial cells were obtained from the ATCC collection. Antiproliferative activity was measured by the MTT test. Immunoblotting was used for the assessment of signaling proteins.

Results

New derivatives of oligomycin A have been obtained using Diels-Alder reactions. Using a screening, a lead derivative of oligomycin A, LCTA-3056, was selected, which is characterized by high selectivity for triple-negative breast cancer cells. Low toxicity of LCTA-3056 was revealed for MCF-10A human mammary epithelial cells. The high activity of combinations of LCTA-3056 with metabolic inhibitors, 3BP and 2DOG, against MDA-MB-231 triple-negative cancer cells was shown. Moreover, the combination of LCTA-3056 with 3BP modulated AMPK/mTOR/S6K pathway and effectively reversed the aggressive EMT phenotype of triple-negative breast cancer cells.

Conclusions

Combinatorial approach with oligomycin A derivatives may hold promise in the development of therapies against triple-negative breast cancers, including those with acquired resistance to standard chemotherapy. The research was supported by the Russian Foundation for Basic Research (# 18-015-00422, experiments with 2DOG) and Russian Science Foundation (#19-15-00245, experiments with MCF-7 cells).

Legal entity responsible for the study

The authors.

Funding

The Russian Foundation for Basic Research (# 18-015-00422, experiments with 2DOG) and Russian Science Foundation (#19-15-00245, experiments with MCF-7 cells).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

78P - Novel allogeneic cell immunotherapy for advanced cancers (ID 518)

Presentation Number
78P
Lecture Time
09:00 - 09:00
Speakers
  • Ratnavelu Kananathan (Nilai, Negeri Sembilan, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immune checkpoint inhibitor (ICI) and CAR-T cell immunotherapies have provided new treatment options for many patients with metastatic disease and hematological malignancy, respectively, inducing durable responses in some cases. CAR-T is not indicated for solid tumors and ICI responsiveness requires high tumor mutational load, CD8+ T cell infiltration and positive IFN-γ status, defining an inflamed phenotype (“hot tumors”). However, the majority of metastatic tumors present as non-inflamed (“cold tumors”), thus limiting the applicability of ICI to a minority subset of patients with highly immunogenic tumors. Immunological treatment of cold tumors is a great challenge as no pre-existing adaptive immune response has been established or maintained.

Methods

AlloStim®, was used on compassionate grounds AlloStim® is currently being evaluated in a phase IIB clinical trial in USA in MSI-S, chemotherapy-refractory, metastatic colorectal cancer patients, an indication known to present with “cold” lesions and to be non-responsive to ICI. AlloStim® is a living, non-genetically manipulated, allogeneic Th1-like cell therapy derived from precursor cells purified, expanded and differentiated from blood of normal donors. The AlloStim® mechanism of action is purported to convert “cold” tumors to “hot” tumors and naturally down-regulate checkpoint molecules in the tumor microenvironment. Single dose vials of formulated AlloStim® cells were delivered to our center in liquid nitrogen dry shippers. Administered either intradermally (ID) or intravenously (IV). The protocol included 3 weekly intradermal (ID) injections followed a week later by an intravenous (IV) infusion. This 4-week cycle was repeated 3 times. Upon approval of our institutional review board and obtaining informed consent.

Results

7 patients were acured 3 advanced/metastatic hepatocellular carcinoma, 2 breast cancer, 1 gall bladder and 1 Nasopharyngeal cancer. Due to the advanced status and poor ECOG status, only 3 completed the treatment schedule. 2 were still stable and alive at 1-year follow-up without receiving any other systemic therapy.

Conclusions

Simple to administer, minimal side-effects and appears to have activity in refractory metastatic disease. Further controlled clinical trials is warranted.

Legal entity responsible for the study

Kananathan.

Funding

Has not received any funding.

Disclosure

M. Har Noy: Leadership role, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Mirror Biologics Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Gastrointestinal tumours, colorectal (ID 1145)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

86P - The impact of sarcopenia on chemotherapy toxicity and survival rate among colorectal cancer patients who underwent chemotherapy: A systematic review and meta-analysis (ID 227)

Presentation Number
86P
Lecture Time
09:00 - 09:00
Speakers
  • Timotius I. Hariyanto (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colorectal cancer (CRC) is the third most commonly diagnosed cancer globally and the second cancer in terms of mortality. The prevalence of sarcopenia in patients with CRC ranges between 12%-60%. It has been described that there is an association between sarcopenia and numerous poor short-term CRC outcomes like increased perioperative mortality, postoperative sepsis, prolonged length of stay, and physical disability. In this study, we review the evidence regarding the impact of sarcopenia and low muscle mass on chemotherapy toxicity and survival among colorectal patients who underwent chemotherapy.

Methods

A systematic review was performed according to PRISMA guidelines. A literature search was conducted by two independent reviewers on all studies that included sarcopenia in colorectal cancer patients who underwent chemotherapy using PubMed, PubMed central, and Google Scholar databases. Study included elderly population was excluded. Outcome of interest included chemotherapy toxicity and overall survival. Data synthesis and statistical analysis were carried out using Review Manager software.

Results

A total of 2206 patients from 14 studies were included in our meta-analysis. In our overall analysis of chemotherapy toxicity, we indicated that CRC patients with sarcopenia would have higher incidence of chemotherapy toxicity (OR = 1.91, 95% CI = 1.37 – 2.67, P < 0.001) including grade 3/4 neutropenia, peripheral neuropathy, nausea and vomiting, also diarrhea. Regarding survival outcomes, our results showed that sarcopenia associated with a decreased overall survival (HR = 1.64, 95% CI 1.36 – 1.98, P < 0.001). These effects of sarcopenia and low muscle mass on chemotherapy toxicity and overall survival were observed among various chemotherapy regimens and across disease stages.

Conclusions

Sarcopenia and low muscle mass can give negative impact on chemotherapy toxicities and survival outcomes for colorectal cancer patients who underwent chemotherapy. Prospective studies with a uniform definition of sarcopenia are still needed to update our findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

87P - Predictive risk factors and online nomograms for colon cancer with synchronous liver metastasis (ID 187)

Presentation Number
87P
Lecture Time
09:00 - 09:00
Speakers
  • Yajuan Zhu (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Liver metastases were observed in more than 25% of colon cancer patients when initially diagnosed. We aim to perform a retrospective analysis to investigate the pathological characteristics and treatment experience of synchronous liver metastasis (CLM) using data from the Population-based Surveillance, Epidemiology, and End Results (SEER) database. Furthermore, we intend to identify potential prognostic factors and build origin predictive models for evaluating 3-year and 5-year cancer-specific survival (CSS) and overall survival (OS) of CLM.

Methods

CLM patients were collected from SEER database between 2010 and 2015. Univariate and multivariate cox regression analyses were conducted to identify the potential predictors of patient’s survival outcomes. The selected variables were integrated to create predictive nomograms via R tools. Furthermore, the concordance index Harrell’s C statistic (C-index) was calculated to describe the discrimination of nomograms. Calibration (1000 bootstrap resamples) curves were plotted to compare predictions of the nomogram and observed outcomes. Subsequently, Decision Curve Analysis (DCA) and clinical impact curves were performed to evaluate the clinical effects of nomograms.

Results

Total 11,812 CLM patients were included after eliminating those with missing information. Tumor primary site, tumor size, histological grade, T /N stage, surgery of other regions, bone/lung metastasis, CEA level, tumor deposits, regional positive nodes, and chemotherapy were used to construct the predictive models of CSS and OS of CLM. Final nomograms indicated relatively good discrimination (C-index = 0.74 for OS and C-index = 0.73 for CSS). The calibration curves of CSS and OS suggested a good agreement. In addition, DCAs and clinical impact curves reflected favorable potential clinical effects. Online webserver of our nomograms was established for convenient utilization (https://predictivetools.shinyapps.io/CSSDynNomapp/;https://predictivetools.shinyapps.io/OS-DynNomapp/).

Conclusions

The nomograms were built on the webserver and validated to effectively and timely predict the CSS and OS of colon cancer patients with synchronous liver metastasis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

88P - Research of radiomics based on indeterminate lung nodules predicting prognosis of LARC patients (ID 327)

Presentation Number
88P
Lecture Time
09:00 - 09:00
Speakers
  • Zhang Zhiyuan (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

With lung remains the second common site of colon-rectal cancer metastasis, it is still a challenge for early detection and finding. Therefore, we evaluate the CT-based radiomics of indeterminate lung nodules, predicting lung metastasis and prognosis in locally advanced rectal cancer patients.

Methods

A retrospective review for lung metastatic patients with colon-rectal cancer (CRC) and chest CT images were conducted. Radiomic prediction model of lung metastasis was trained by 114 patients with pathologically verified lung metastasis and 122 patients with benign lung nodules. We investigate the value of radiomics for identifying lung metastasis in 174 locally advanced rectal cancer(LARC) patients with follow-up information. Then, we conducted a Cox model and Kaplan-Meier curve analysis based on radiomics risk scores, and compare them to a clinical-pathological model for prognostic prediction. We use LASSO and linear regression to generated the radiomics model. C-index was used to assess model performance.

Results

For lung metastatic nodule identification in CRC patient, the C-index was 0.794(95%CI 0.784 -0.803) in the training set and 0.752(95%CI 0.728-0.776) in the validation set. In LARC patients, the C-index for lung metastatic identification was 0.771(95%CI 0.763-0.780). For prognostic prediction in LARC patients, ypTNM stage had a great influence on prognosis(Log-rank test P=0.003), and the C-index was 0.695 (95%CI 0.638-0.752). The C-index for nodules was 0.663(95%CI 0.575-0.751) with HR=1.148 (95% 1.050-1.256, P=0.003), and P<0.001 for Log-rank test. The combination of the ypTNM stage and nodule radiomics information has the C-index of 0.757 (95%CI 0.692-0.822), with P<0.001 for Log-rank test, which increase the performance of clinical prognostic prediction(P= 0.044).

Conclusions

Radiomics for nodules can determine lung metastasis in LARC patients. Lung nodules radiomics can provide information for prognostic analysis. The combination of lung nodules radiomics and ypTNM information increases the performance of prognostic prediction in LARC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

89P - Biomarker analysis of regorafenib dose escalation study (RECC study): A phase II multicenter clinical trial in Japan (ID 491)

Presentation Number
89P
Lecture Time
09:00 - 09:00
Speakers
  • Masanobu Enomoto (Shinjuku-ku, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

RAS status can impact on efficacy of chemotherapy for patients with metastatic tumor. However, we reported that RAS mutated clone can emerge in patients with RAS wild tumor, which suggest that the genotype of the tissue obtained at the time of diagnosis might not accurately represent, who are treated with EGFR blockade. In this study, we evaluated whether RAS mutation in tissue and/or in circulating tumor DNA (ctDNA) impact on efficacy of regorafenib. This is the biomarker analysis of RECC study, a phase II multicenter clinical trial in Japan, that confirmed the safety and effectiveness of dose escalation therapy of regorafenib in metastatic colorectal cancer (mCRC).

Methods

We conducted dose-escalation study as a single-arm, prospective, non-randomized, multi-centered open label phase II trial in Japan (RECC study). We set a starting dose of 80 mg/day during the first seven days, then will be increased up to 120 or 160 mg/day weekly. Before first administration of regorafenib, we extracted ctDNA and examined RAS mutation in ctDNA using droplet digital PCR (ddPCR).

Results

Fifty-eight patients with mCRC were registered in this study, and blood samples were available in 45 patients. In all obtained samples, ctDNA were successfully extracted from plasma and the quality and quantity of ctDNA were sufficient for genetic analysis. RAS mutation was detected in tumor tissue of 29 patients (64%) and in ctDNA of 21 patients (47%). In ctDNA, RAS mutation was detected in 21 of the 29 patients (72%) with RAS mutated tumor, and 6 of 16 patients with RAS wild tumor. Five of the 6 patients with RAS wild tumor were treated with EGFR blockade in previous treatment. RAS status both in tumor tissue and ctDNA had no impact on progression free survival and overall survival.

Conclusions

It was reported that RAS mutation has negative impact on efficacy of FTD/TPI. However, RAS mutation showed no impact on the efficacy of regorafenib. EGFR blockade have a potential to emerge RAS mutated clone. Thus, RAS status should be reconfirmed at the last minute before starting late line chemotherapy using liquid biopsy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

90P - The role of miR-133a-3p/SP1/IGF1R axis in the progression of colorectal cancer (ID 519)

Presentation Number
90P
Lecture Time
09:00 - 09:00
Speakers
  • Hui Li (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. MicroRNA has been reported playing an important role in a variety of cancers including colorectal cancer.

Methods

CRC tissues as well as CRC cell lineswere used to evalute the expression and function of miR-133a-3p, SP1 and IGF1R. The relationship between miR-133a-3p and clinical-pathological charateristics of CRC patients were analyzed. The interaction among miR-133a-3p/SP1/IGF1R was assessed using Dual Luciferase reporter.

Results

MiR-133a-3p has been found down-regulated in CRC tissues compared with the adjacent normal tissues. The expression of miR-133a-3p was significantly associated with histological differentiation (P=0.01) and TNM stage (P=0.006) respectively. CRC patients with low miR-133a-3p expression had a significantly shorter survival time than those patients with high miR-133a-3p expression (P=0.04). Gain-of-function assays showed that miR-133a-3p inhibited cellular proliferation and colony formation, but had no effect on migration and invasion of CRC cells. Furthermore, expression of SP1 and IGF1R was reduced by elevating miR-133a-3p expression in CRC cells. Luciferase assay further confirmed that SP1 but not IGF1R was the target gene of miR-133-3p and SP1 could bind to the promoter region of IGF1R gene.

Conclusions

In summary, our findings first demonstrate that miR-133a-3p acts as a tumor suppressor by targeting SP1 and miR-133a-3p/SP1/IGF1R signaling pathway is involved in CRC progression. MiR-133a-3p may be a novel molecular therapeutic target for CRC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

91P - Prognostic biomarker of clinical outcome in locally advanced rectal cancer in Chinese patients (ID 576)

Presentation Number
91P
Lecture Time
09:00 - 09:00
Speakers
  • Sandy S. Ho (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neoadjuvant chemoradiotherapy (NCRT) is one of the standard treatments for locally advanced rectal cancer (LARC), where pathological complete response (ypCR) has been traditionally used as a surrogate survival endpoint. A relatively new biomarker known as the Neoadjuvant Rectal (NAR) score has been consistently shown to correlate with survival in clinical studies. NAR score is a composite endpoint combining clinical and pathological staging information obtained before and after NCRT which warrants validation in local population. The main objective of this study is to investigate the factors that may influence the achievement of ypCR, such as age, sex, tumour stage and location, presence of threatened CRM and extramural vascular invasion (EMVI) as well as tumour down-staging. Other objectives are to validate the prognostic significance of NAR score and to investigate any factors that are associated with a lower score.

Methods

The data of patients with LARC who received NCRT at the Prince of Wales Hospital between August 2006 to October 2018 were retrospectively analyzed. Chi-square or Fisher’s Exact Test was used to determine any correlation between categorical variables and logistic regression for continuous variables. Cox regression was used to determine any interactions between covariates and Kaplan-Meier method for survival analysis.

Results

Of the 193 patients who had optimal response to NCRT and surgery, the mean age was 62 and the male-to-female ratio was 2.94: 1. Tumour down-staging was the only independent prognostic factor which predicted ypCR (p<0.0001). NAR score was associated with overall survival (OS) (hazard ratio, HR=1.042, 95% confidence interval, CI: 1.021-1.064, p<0.0001), disease-free survival (DFS) (HR=1.042, 95% CI: 1.022-1.062, p<0.0001), locoregional recurrence-free survival (LRFS) (HR=1.070, 95% CI:1.039-1.102, p<0.0001) and distant recurrence-free survival (DRFS) (HR=1.034, 95%CI: 1.012-1.056, p=0.002). Patients who had ypCR to NCRT was associated with a lower NAR score (p<0.0001), but ypCR was not associated with survival.

Conclusions

NAR score (but not ypCR) is an independent prognostic marker of survival and disease recurrence in a cohort of Chinese patients who underwent NCRT for LARC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

92P - Development and validation of risk and prognostic nomograms for bone metastases in advanced colorectal cancer patients (ID 665)

Presentation Number
92P
Lecture Time
09:00 - 09:00
Speakers
  • Nan Wang (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bone metastases (BM) from colorectal cancer (CRC) are often accompanied by extraosseous metastases and have a dismal prognosis. The present study aims to find out the risk factors for BM in metastatic CRC (mCRC) and the prognostic factors for CRC patients with BM.

Methods

The study was based on a training cohort of 214 mCRC patients (of which 101 patients with BM) from our center, and a validation cohort of 511 mCRC patients from another institution (of which 173 patients with BM). The risk and prognostic nomogram for BM were identified using univariate and multivariate analyses. The goodness of fit, discrimination and calibration performance of the nomograms were assessed by R2, concordance statistics (C-statistics) and the calibration curve. The results were internally validated using bootstrap resampling in the training cohort and externally validated in the validation cohort.

Results

The novel BM risk nomogram comprised of seven variables (degree of tumor differentiation, N_stage, serum ALP, LDH, CEA, liver metastasis and lung metastasis). It showed good performance with an R2 of 0.447 and a C-statistics of 0.846 (95% CI, 0.793 to 0.898) in the training cohort, and an R2 of 0.325 and a C-statistics of 0.792 (95% CI, 0.750 to 0.834) in the validation cohort. The optimal cutoff value to identify individuals at low or high risk was 56% probability with the sensitivity of 71.3% and specificity of 89.4%. The prognostic nomogram included five factors (tumor differentiation, No. of extra-BM organs, No. of BM lesions, ALP and LDH) with an R2 of 0.284 and a C-statistics of 0.723 (95% CI, 0.657 to 0.789) in the training set. This nomogram was externally validated in the validation cohort with an R2 of 0.182 and a C-statistics of 0.682 (95% CI, 0.638 to 0.726).

Conclusions

The developed and validated risk nomogram and prognostic nomogram show good performance on predicting the occurrence of BM in mCRC and prognosis in CRC patients suffered from BM. The risk nomogram can be used as a cost-effective preliminary screening tool prior to bone scan.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

93P - Assessment of nutritional status of colorectal cancer patients in a tertiary government hospital (ID 787)

Presentation Number
93P
Lecture Time
09:00 - 09:00
Speakers
  • Rogelio N. Velasco (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Malnutrition, a problem often missed among patients with colorectal cancer, can result in decreased survival. However, its prevalence has not yet been evaluated in our institution. This study aimed to determine the nutritional status among patients with colorectal cancer at the Philippine General Hospital and identify predictors for malnutrition.

Methods

A cross-sectional study was conducted among all patients with colorectal cancer seen at the Philippine General Hospital Cancer Institute between December 2019 to February 2020. Anthropometric measurements were taken and nutritional status was evaluated using the Subjective Global Assessment tool. Descriptive statistics, ANOVA and logistic regression were employed to analyze the data.

Results

A total of 292 participants were included in the study with a high prevalence of cachexia (25.34%), sarcopenia (31.16%), and malnutrition (76.37%). Notably, only 17% of patients were referred by oncologists to the dietary service. The presence of liver metastasis and multiple sites of metastases were associated with increasing degree of malnutrition across SGA B and C (p = 0.05). Additionally, more patients with lung and peritoneal metastases were classified as malnourished (p = 0.05). Patients who did not receive chemotherapy, radiation, or surgery were more likely to be malnourished compared to those who previously received or were currently receiving treatment (chemotherapy: p < 0.01; radiation: p = 0.04; surgery: p < 0.01). Furthermore, patients with stage III disease had a higher odds for malnutrition (OR: 6.22, p < 0.01) compared to those with stage I and II disease, while patients who received or were currently receiving chemotherapy were less likely to have malnutrition than those who did not (OR: 0.35, p < 0.01).

Conclusions

Due to the high prevalence of malnutrition among patients with colorectal cancer, routine nutritional evaluation is important. Moreover, the high prevalence of cachexia and sarcopenia warrants early and adequate nutritional intervention. Thus, a hospital-wide program focusing on early nutritional assessment is recommended for implementation.

Legal entity responsible for the study

The authors.

Funding

Philippine General Hospital.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

94P - Prognostic influence of mean platelet volume on stage III rectal cancer patients: A tertiary cancer center study (ID 390)

Presentation Number
94P
Lecture Time
09:00 - 09:00
Speakers
  • Pavan K. Jonnada (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Mean platelet volume (MPV) is a marker of inflammation that indicates the average size of platelets, platelet production rate and stimulation. The role of Pre-operative levels of MPV and its prognostic effect on disease free survival (DFS) and overall survival (OS) are poorly understood. This study was intended to analyze the effect of pre-operative levels of MPV on DFS and OS of stage III rectal cancer patients.

Methods

This is a retrospective study of 149 stage III rectal cancer patients who underwent surgery in our institution between 2011 and 2015. Association between pre-operative levels of MPV and clinicopathological variables were analysed. DFS and OS for 5 years were analysed, and survival analysis was done using Kaplan-Meier curve. MPV of 9.35 femto litres (fl) was chosen based on the ROC curve. The Area under curve was 0.889. Differences between survival curves were analysed for statistical significance using log-rank test.

Results

In our study, mean 5-year OS were 91.1 and 50.36 months, for patients with MPV < 9.35 and MPV >9.35 respectively (P 0.0001). The mean DFS of MPV < 9.35 and MPV > 9.35 were 89.32 and 43.54 months respectively (P 0.0001). Univariate analysis for OS and DFS showed significance for MPV, Nodal status, Circumferential resection margin, stage and lymph node ratio. Multivariate analysis showed significance for MPV [HR 2.379 (95% CI 1.733-3.264) P .0001 for MPV>9.35] and CRM [HR 0.392 (95% CI 0.191-0.804) P 0.01) for CRM negative] for OS and DFS. Multivariate Analysis for OS & DFS

Variable OS DFS
P value Hazard Ratio 95% CI P value Hazard Ratio 95% CI
Lower Upper Lower Upper
N Stage
N1a .782 .785 .140 4.390 .824 .833 .167 4.146
N1b .119 .322 .077 1.340 .159 .389 .104 1.448
N2a .554 .715 .235 2.175 .680 .810 .297 2.209
N2b Reference Reference
CRM
Negative .011 .392 .191 .804 .012 .412 .207 .821
Positive Reference Reference
Stage
IIIA .568 .692 .196 2.447 .203 .465 .143 1.510
IIIB .474 .727 .303 1.743 .203 .607 .281 1.310
IIIC Reference Reference
MPV
>9.35 .0001 2.379 1.733 3.264 .0001 2.370 1.791 3.136
<9.35 Reference Reference
LNR ratio
>0.2 .220 3.269 .492 21.738 .059 5.756 .938 35.327
<0.2 Reference Reference
.

Conclusions

Pre-operative MPV measured one week before surgery is a convenient and inexpensive marker which has been proved to be a prognostic marker for OS and DFS in stage III rectal cancer patients.

Legal entity responsible for the study

Kidwai Memorial Institute of Oncology, Bangalore, India.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

95P - Prognosis of Japanese patients with detailed RAS/BRAF mutant colorectal cancer (ID 427)

Presentation Number
95P
Lecture Time
09:00 - 09:00
Speakers
  • Tatsuki Ikoma (Kobe, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

RAS mutations are the most prominent oncogenic driver mutations in cancers, including colorectal cancer. Patients with metastatic colorectal cancer (mCRC) with mutant RAS are ineligible for anti-epidermal growth factor receptor (EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. In particular, mutations in the amino acid at position 12 in the KRAS protein are common, and the KRAS p.G12C mutation occurs in ∼3% of CRC cases and is often associated with poor prognosis. Nevertheless, no agent directly targeting mutant RAS has been clinically approved. The CodeBreak 100 trial revealed that a novel KRASG12C inhibitor, AMG510, has an attractive anti-tumor effect against KRASG12C-mutant solid tumors, including mCRC. However, there are no data about the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC including KRASG12C. The aim of this multicenter retrospective study was to investigate the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC.

Methods

Between August 2018 and July 2019, chemotherapy-naïve patients with mCRC from whom samples were collected and investigated for all RAS/BRAFV600E statuses were included in this study. The RAS/BRAFV600E status was determined using the MEBGEN RASKET-B kit, PCR-rSSO method.

Results

In total, 152 patients with mCRC (median age, 71 years; male, 71%; left-sided primary, 67.1%) were enrolled from three tertiary cancer centers. Of the patients, RAS/BRAF mutations were detected in 54.6% (KRAS codon 12, 27.0%; KRAS codon 13, 11.8%; minor RAS, 9.2%; BRAFV600E, 6.6%). BRAFV600E-mutant tumors were predominantly located on the right side (77.8%, p=0.005), and minor RAS-mutant tumors were located predominantly on the left side (92.9%, p=0.037). Minor RAS-mutant tumors were associated with significantly shorter survival times than those associated with RAS wild-type {hazard ratio (HR)=2.65 [95% confidence interval (CI), 0.99 to 7.07], p=0.043} and major RAS-mutant tumors (HR=5.15 [95% CI, 1.56 to 16.98], p=0.003).

Conclusions

This multicenter study revealed the clinical and prognostic features in Japanese patients with detailed RAS/BRAFV600E-mutant mCRC.

Legal entity responsible for the study

Hironaga Satake.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

96P - Early-onset colorectal cancer prognosis, conflict resolution, review of literature and meta-analysis (ID 817)

Presentation Number
96P
Lecture Time
09:00 - 09:00
Speakers
  • Ereny S. Poles (Assiut, Egypt)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Early-onset colorectal cancer (EOCRC) is defined as colorectal cancer diagnosed in individuals younger than 50 years old. There is a concept that EOCRC is associated with a worse survival, while the data on literature is conflicting. Evaluation of the available data is highly needed to reach an evidence-based conclusion.

Methods

A systematic literature search was performed using Scopus (2015-2020), CENTRAL PubMed (2015-2020) for studies assessed prognosis of EOCRC in comparison with LOCRC using the relative 5-year survival (OS) as a surrogate for prognosis. Extracted information included: study identification, number of EOCRC and LOCRC patients, AJCC stage, and overall 5-year survival. Keywords and Mesh words used: prognosis, outcome, survival, young, early-onset, age of onset, colorectal cancer, rectal cancer, colon cancer. Statistical analysis was done using MedCalc Statistical Software for the meta-analysis.

Results

Meta-analysis for a total of 428554 LOCRC and 670030 EOCRC patients of the included 9 studies showed no statistically significant difference in male ( P= 0.19 ) or female ( P= 0.20 ) as regards the incidence EOCRC when compared to LOCRC. Younger adults were1.2 more likely to present with left-sided and rectal cancer ( OR;1.20, 95% CI, 0.18 to 7.86, P= 0.84 ) than older patients, while the right colon cancer was less presented by 79% in EOCRC patients (OR; 0.79, 95%CI, 0.05 to 11.13, P= 0.86). Stage I disease was statistically significant less diagnosed in EOROC than LOCRC patients ( P< 0.001, 95%CI, 0.31 to 0.70 ), while there were no statistically significant differences for stages II, III, and IV, ( P= 0.27, 95%CI, 0.03 to 2.58), ( P= 0.84, 95%CI, 0.03 to 4.57) and ( P= 0.70, 95%CI, 0.10 to 4.62 ) respectively. There was no difference in the 5 year OS between EOCRC and LOCRC patients ( P= 0.62, 95%CI, -0.004 to 0.002). Subgroup analysis based on the stage showed a better survival in EOCRC patients in all stage groups; ( P= 0.03, 95%CI,1.34 to 21.19) for stage I, (P, 0.001, 95%CI, 2.38 to 3.64) for stage II, (P< 0.001, 95%CI, 2.20 to 4.80) for stage III, and (P= 0.009, 95%CI, 1.62 to 28.79) for stage IV.

Conclusions

EOCRC patients had a similar 5-year OS when compared to LOCRC while had a better 5-year OS when corrected for the disease stage.

Legal entity responsible for the study

The authors.

Funding

Quality Control Unit, Faculty of Medicine, Assiut University.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

97P - A population-based study to assess the associations of rural residence and low socioeconomic status (SES) with cardiovascular disease (CVD) in patients with colorectal cancer (CRC) (ID 252)

Presentation Number
97P
Lecture Time
09:00 - 09:00
Speakers
  • Atul Batra (New Delhi, Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients with CRC are predisposed to CVD due to shared risk factors and sequalae of cancer treatments. We aimed to assess if rural residence and low SES modify the risk of developing new-onset CVD in patients with CRC.

Methods

Patients diagnosed with stage I-III CRC without any baseline CVD in a large Canadian province from 2004 to 2017 were identified using the population-based registry. Postal codes were linked with Census data to determine rural residence as well as SES. Low income and low education were defined as <46,000 CAD/annum and a neighborhood population in which <80% attended high school. The presence of myocardial infarction, heart failure, arrythmia or cerebrovascular accident constituted as CVD.

Results

We identified 12,170 eligible patients. The median age was 65 years and 43.7% were women. Stage I, II and III CRC were diagnosed in 30.2%, 31.4% and 38.5% patients. One-fourth of patients resided rurally, while 78.8% and 59.5% belonged to low income and low education neighborhoods. At a median follow-up of 62.2 months, 4,163 (34.2%) developed new-onset CVD, which was more common in patients from rural communities (36.8% vs 33.3%, P<.001), low income (35.7% vs 28.8%, P<.001) and low education (36.0% vs 31.6%, P<.001) neighborhoods. After adjusting for age, sex and treatment, low income (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10-1.37; P<.001) and low education (OR, 1.10; 95% CI, 1.01-1.20; P=.044) were associated with a higher likelihood of developing CVD, while rural residence was not. In a Cox regression model adjusting for measured confounders, low income (hazard ratio, 1.14; 95% CI, 1.03-1.25; P=.010) but not low education and rural residence predicted for worse overall.

Conclusions

In this large population-based study, patients from low SES neighborhoods were at an increased risk of developing new-onset CVD. However, the effect on survival was attenuated, likely reflecting access to universal healthcare in Canada. SES disparities in physical activity, diet, and other lifestyle modification strategies may explain the different risk profiles for CVD and should be the focus of public health efforts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

98P - Operational challenges of an Asian Pacific (APAC) academic oncology clinical trial (ID 928)

Presentation Number
98P
Lecture Time
09:00 - 09:00
Speakers
  • Daphne Day (Clayton, Ontario, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Multinational academic trials can pose complex organisational issues. We describe our experience running the phase III ASCOLT trial (NCT00565708), studying the impact of aspirin in resected high-risk colorectal cancer. This is the first large academic adjuvant trial fully conducted in the APAC region.

Methods

ASCOLT is coordinated by the National Cancer Centre Singapore and funded largely by academic grants. The trial opened in 2008 and is nearing full accrual (1480 of 1587) at 58 sites in 12 countries/regions, including 5 middle income countries. Trial conduct logistics were analysed to identify barriers and enablers.

Results

Diverse regulatory requirements necessitated >100 contracts and 49 ethics board reviews, leading to start up times of ∼6 months per site. Consent forms were translated into 13 languages. The enrolment target and period were revised in 2017, and site numbers expanded due to lower than projected accrual and event rates. Other challenges include communication and logistical barriers, patient attrition, recruitment holds due to changes in local laws and limited funding for patient visits, affecting countries where healthcare is not publicly funded. Solutions included engaging local cooperative groups (e.g. the Australasian GastroIntestinal Trials Group in Australia and New Zealand) and 6 contract research organisations to manage sites, developing processes sensitive to local needs, transition to electronic data management, and a centralised drug dispensing system. Measures to overcome disparate experience across sites and to quality control include regular contact with the central team to troubleshoot (e.g. >200 data queries are raised a month) and central and on-site monitoring. 16 sites were closed due to resource or recruitment issues. In response to the COVID-19 pandemic, strategies such as telehealth consults, direct postage of drugs to patients, consent form amendments, and rationalised recruitment and biospecimen collection were swiftly applied.

Conclusions

While ASCOLT highlights the feasibility and value of APAC academic collaborative trials, our challenges reflect the complexities in a region of cultural, linguistic, economic and regulatory diversity. An APAC academic trials consortium is suggested.

Clinical trial identification

NCT00565708.

Legal entity responsible for the study

National Cancer Centre Singapore.

Funding

National Cancer Centre Singapore.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

99P - Development of a qRT-PCR-based diagnostic test to identify colorectal cancer patients with recurrent R-Spondin gene fusions (ID 245)

Presentation Number
99P
Lecture Time
09:00 - 09:00
Speakers
  • Veronica Diermayr (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In colorectal cancers (CRC) 4 different recurrent gene fusions involving R-Spondin (RSPO)2/3 and different exons of PTPRK or EIF3E are found with around 4% incidence. These fusions (Fusion A-D) occur exclusively in a sub-population of CRC with high unmet medical need that is microsatellite-stable (MSS) and mutant for KRAS, NRAS or BRAF but wild-type (WT) for APC. RSPO-fusions are known driver mutations, increasing Wnt signalling and sensitizing for treatment with upstream Wnt pathway inhibitors. Detection of the fusions is possible using Archer FusionPlex technology, but with low sensitivity. A multiplex reverse transcription, real-time PCR-based test, specific for the detection of recurrent RSPO fusions, was developed as a Clinical Trial Assay (CTA).

Methods

The CTA uses RNA extracted from FFPE or frozen tumor tissue in a qRT-PCR, simultaneously detecting the RSPO fusion, the WT fusion partner(s), and an internal control. The assays span exon-exon junctions to increase selectivity and amplify fragments of 80-140 bp in length to allow for detection in RNA extracted from FFPE tissue. A ΔCt is calculated by subtracting the Ct of the WT reaction (PTPRK or EIF3E) from the RSPO fusion Ct. Values below or equal to the set cut-off permit qualitative calling of samples positive for the fusions.

Results

180 fresh frozen and 118 FFPE samples from CRC patients were used in the analytical validation for the 4 CTAs. All assays show high precision (100%) at the limit of detection (LoD) and high specificity in terms of residual EtOH (≤4%) or EDTA (<5 mM). Sensitivity was high with the LoD for Fusions A-D between 1.46-5.10% for frozen tissue and 2.82%-21.6% for FFPE, respectively. The assays also showed high accuracy and 100% concordance with Sanger sequencing for fusion positive samples (with a ΔCt cut-off of ≤13-15 and ≤5-7.5 for frozen and FFPE tissue, respectively).

Conclusions

The RSPO Fusion CTA is a quick and cost-effective test with high sensitivity (RNA input of 5 or 25 ng for frozen and FFPE tissue respectively). This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA.

Clinical trial identification

NCT02521844.

Legal entity responsible for the study

Experimental Drug Development Centre, A*STAR.

Funding

BMRC, NRF and NMRC Singapore.

Disclosure

V. Diermayr: Research grant/Funding (institution), Full/Part-time employment: A*STAR. S. Sarma, K.F.Y. Lee, B.H. Gan: Full/Part-time employment: A*STAR. M. Inoue: Licensing/Royalties, Full/Part-time employment: A*STAR. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

100P - Individualized treatment of advanced digestive system tumour guided by PDTX mouse model: A multicenter trial (ID 499)

Presentation Number
100P
Lecture Time
09:00 - 09:00
Speakers
  • Yuan Cheng (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To explore the clinical feasibility of the patient-derived tumor xenograft (PDTX or PDX) mouse model in guiding the individualized precise treatment of advanced digestive system tumors through a multicenter clinical study.

Methods

14 centers participated the trial in China. Fresh tumor tissues were obtained by surgery and biopsy, then engrafted subcutaneously into immune deficient mice. When the tumor volume grew to 60 mm3, the modeling was successful. The consistency of the original tissue (PA) and the engrafted tissue (P0) was analyzed by pathological comparison. The tumorigenesis time model was recorded. After successful modeling, medication was administered in groups according to the recommended regimen for 21 days. The tumor growth inhibition rate (TGI) was recorded and evaluated as positive if TGI > 60%. According to RECIST 1.1, DCR (SD, PR, CR) was evaluated as positive in clinical synchronous treatment. The two results were compared to evaluate the accuracy of guiding clinical medication.

Results

A total of 33 patients with different advanced digestive system tumors were included, including 2 cases of esophageal cancer, 10 cases of colorectal cancer, 10 cases of pancreatic cancer, 5 cases of gastric cancer, 3 cases of liver cancer, 2 cases of duodenal adenocarcinoma and 1 case of gallbladder cancer. The successful rate of tumor xenograft modeling was 75.8% (25/33), including 78.3% (18/23) in small samples and 70% (7/10) in surgical samples. Pathological results showed that the consistency of P0 and PA was 100% in 25 cases. The average tumorigenesis time of PDTX model was 42 days. Pharmacodynamic tests were completed in 17 cases, including 28 kinds of drugs and 49 regimens. The clinical efficacy of 10 regimens in 9 patients were evaluated as PR in 2 cases, SD in 6 cases and PD in 2 cases. The results of pharmacodynamic test were consistent with clinical synchronous efficacy.

Conclusions

PDTX mouse model has high successful modeling rate with the biological and pathological characteristics of primary tumor, and the results of pharmacodynamic test are highly consistent with the clinical efficacy. It can be used as a individualized diagnosis and treatment technique of advanced gastrointestinal tumors.

Legal entity responsible for the study

The authors.

Funding

Nanjing Personal Oncology Biotechnology Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

101P - HIF1-α depletion overcomes resistance to oxaliplatin in colorectal cancer via ERK signalling pathway (ID 551)

Presentation Number
101P
Lecture Time
09:00 - 09:00
Speakers
  • Se Jun Park (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemoresistance is a major reason for treatment failure and results in poor prognosis in patients with advanced colorectal cancer (CRC). Hypoxia-inducible factor-1 (HIF1-α) is a regulator of the transcriptional response to oxygen deprivation in cancer cells and activates the transcription of genes that are involved in angiogenesis, cell survival and invasion. However, the effect of HIF1-α activation on oxaliplatin resistance in CRC is unclear. This study aimed to investigate the effects and potential mechanism of HIF1-α on oxaliplatin resistance in CRC.

Methods

Oxaliplatin-resistant cells were generated from HCT116 cells. Cell Counting Kit-8, flow cytometry, Transwell assay were used to compare the characteristics of oxaliplatin resistant HCT116 (HCT116_OxR) cells and the corresponding parental HCT116 cells. The expression of HIF1-α, extracellular signal-related kinase (ERK), and transforming growth factor β (TGFβ) were confirmed by RT-PCR and western blotting in HCT116_OxR and HCT116 cells. Next, we evaluated the combination efficacy of inhibitors of HIF1-α (YC-1), ERK (Ravoxertinib), and TGFβ1 (SB431542) with oxaliplatin by in vitro and in vivo experiments.

Results

We found that cell viability of HCT116_OxR was higher than that in parental cells in the presence of oxaliplatin. The relative expression of HIF1-α was significantly increased in HCT116_OxR cells compared with the parental HCT116 cells. Downregulation of HIF1-α in HCT116_OxR cells increased oxaliplatin sensitivity, and diminished cell survival and invasion. Significantly, ERK signaling in HCT116_OxR cells is dependent on TGFβ1, promoting oxaliplatin resistance by activating HIF1-α. Inhibition of ERK by Ravoxertinib or TGFβ1 by SB431542 efficiently overcame oxaliplatin resistance in vitro and in vivo.

Conclusions

HIF1-α activation is regulated by TGFβ1/ERK axis in HCT116_OxR cells. Hence, HIF1-α, ERK, and TGFβ1 are potential therapeutic targets for overcoming oxaliplatin resistance in patients with CRC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

102P - Colorectal cancer organoids culture exploits new neoadjuvant therapy resistance mechanisms and therapeutic targets (ID 1007)

Presentation Number
102P
Lecture Time
09:00 - 09:00
Speakers
  • Yun Deng (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumor organoids are a state of the art platform for precision medicine. With more and more studies showing that the treatment in organoids in vitro perfectly matches the patients' response, tumor organoids could predict patients' responses in clinical settings, including for colorectal cancer, pancreatic cancer, and ovarian cancer. Based on these studies, comparing the genetic data from the tumor organoids should be a strategy to investigate treatment resistance mechanisms and exploit new therapeutic targets.

Methods

Tumor organoids were obtained from our colorectal cancer organoids bank. RNA sequencing analysis was used to screen potential markers that play pivotal roles in mediating treatment response based on the organoids' response to drug treatment and radiation. Candidate genes were analyzed by qPCR, and CRISPR technology was applied to investigate the gene function in cell lines and organoids.

Results

We found several differentially expressed genes between sensitive and resistant organoid groups of which most were metabolism related. Among them, GPX2 and FREM1 were highly expressed in colorectal cancer and could prompt cell proliferation and growth. GPX2 and FREM1 are found to tightly influence treatment with 5-FU and irinotecan, respectively, in colorectal cancer cells, higher GPX2 could enhance the IC50 of 5-FU, while FREM1 increases the IC50 of irinotecan in colorectal cancer cells, and both of them could increase radiation resistance. Overexpressing GPX2 could decrease cellular ROS levels, increase stem cell marker CD24 level and EMT transition, while FREM1 could activate the NF-KB signaling and inhibit cell apoptosis included by radiation and drug treatment.

Conclusions

Tumor organoids could be useful to explore new therapeutic targets in cancer treatment with higher precision. GPX2 and FREM1 which are upregulated in colorectal cancer increase cell proliferation and growth, cause radioresistance. GPX2 is related to 5-FU resistance while FREM1 is related to irinotecan resistance in colorectal cancer cells. These results imply these two molecules could be new therapeutic targets in the treatment of colorectal cancer.

Legal entity responsible for the study

Zhen Zhang.

Funding

National Natural Science Foundation of China, 81773357.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

103P - Comprehensive genomic landscape in younger and older Chinese patients with colorectal cancer (ID 826)

Presentation Number
103P
Lecture Time
09:00 - 09:00
Speakers
  • Huina Wang (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The incidence of colorectal cancer (CRC) in young patients is increasing in recent years. However, the difference of genomic landscape between younger and older patients with CRC are poorly investigated and has never been reported in Chinese population.

Methods

A total of 75 CRC patients were enrolled. All kinds of genetic alterations were analyzed by next-generation sequencing (NGS) with Acornmed panel.

Results

Genomic landscape exhibited notable differences between younger and older CRC groups. APC and PIK3CA alterations were more commonly altered in older tumors (p < 0.05), while SMAD4 mutations tended to occur in younger tumors (p = 0.054). Notably, mutational distributions of KRAS in younger group differed from those in older group, and a higher prevalence of KRAS codon 12 alterations was potentially associated with young age (p = 0.076). Furthermore, the majority of patients (77.3%) harbored at least one clinically actionable alteration, and targeted genetic profiles between younger and older patients were significantly different (p < 0.05). Additionally, in patients with mismatch repair-proficient and mscirosatellite-stable (pMMR/MSS) CRC, tumor mutational burden (TMB) was positively correlated with age (p < 0.05), and a significantly association was found between high TMB and DNA damage response (DDR) pathway alterations (p < 0.05).

Conclusions

This study revealed different molecular profiles between younger and older Chinese patients with CRC, which provided novel insights into the personalized therapy in CRC.

Legal entity responsible for the study

Acornmed Biotechnology Co., Ltd.

Funding

Has not received any funding.

Disclosure

H. Wang, H. Cheng, T. Zhou, F. Lou, S. Cao: Full/Part-time employment: Acornmed Biotechnology Co., Ltd.

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e-Poster Display Session (ID 87) Poster Display

104P - Safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment for metastatic colorectal cancer: A randomised, double-blind phase III study (ID 674)

Presentation Number
104P
Lecture Time
09:00 - 09:00
Speakers
  • Shukui Qin (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HLX04, a proposed bevacizumab biosimilar, was developed stepwise with proven analytical and clinical PK similarities. This confirmatory ph3 study (NCT03511963) aimed to compare the safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment in pts with recurrent/metastatic colorectal cancer.

Methods

We conducted this double-blind, multicentre, parallel-controlled, ph3 study (HLX04-mCRC03) in pts (18≤age≤75 years) with histologically/cytologically confirmed unresectable recurrent/metastatic CRC. Eligible subjects were randomised 1:1 to receive either HLX04 or bevacizumab intravenously (7.5 mg/kg Q3W in combination with XELOX or 5 mg/kg Q2W in combination with mFOLFOX6). The primary endpoint was the progression free survival rate at week 36 (PFSR36w) per RECIST v1.1. Secondary endpoints included ORR, 12-month OS rate and DoR. Primary and secondary endpoints were further stratified (by chemotherapy, KRAS/BARF mutation, etc.) for subgroup analyses.

Results

PFSR36w was 46.4% (n=338) in HLX04 and 50.7% (n=337) in bevacizumab per FAS. The group difference was -4.2% (90% CI -10.6%, 2.1%), which fell entirely in the pre-defined equivalence margins (-11%, 15%). No statistically significant difference was observed in primary or secondary endpoints and their subgroup analyses. Similar safety results were demonstrated between the two treatment groups. The most common TEAEs (grade≥3) in both groups were decreased neutrophil count (20.6% vs 20.2%), decreased platelet count (10.3% vs 10.1%) and hypertension (7.4% vs 12.5%). The most common SAEs in both groups were intestinal obstruction (9.0% vs 9.6%) and decreased platelet count (11.2% vs 6.7%). The incidences of death during the treatment was 11 (3.2%) and 9 (2.7%), respectively. The immunogenicity profiles were similar between treatment groups.

Conclusions

HLX04 demonstrated equivalent efficacy and similar safety and immunogenicity profiles with reference bevacizumab as first-line treatment for mCRC, presenting as an alternative option for cancer pts as a biosimilar candidate.

Clinical trial identification

NCT03511963; April 30, 2018.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

L. Zhang, W. Li, K. Chai: Full/Part-time employment: Shanghai Henlius Biotech, Inc. W. Jiang, S. Liu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

105P - Prospective, open-label, observational study of cetuximab for metastatic colorectal carcinoma (mCRC): The OPTIM1SE study (ID 903)

Presentation Number
105P
Lecture Time
09:00 - 09:00
Speakers
  • Tsai-Sheng Yang (Taipei, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Cetuximab-based infusional 5-FU regimens are approved for the first-line treatment of mCRC in 116 countries. The OPTIM1SE study observed long-term real-world outcomes of these regimens in routine practice in Australia, South Korea, Malaysia, Singapore, Taiwan, Vietnam, Russia, Lebanon, and Saudi Arabia.

Methods

OPTIM1SE was a prospective, open-label, observational study. Patients with untreated KRAS wild-type mCRC and distant metastases were treated per the locally approved label and monitored for 3 years via hospital, laboratory, and other records. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Safety and other efficacy outcomes were secondary endpoints.

Results

From 19 Nov 2013 to 30 Jun 2016, 520 patients were enrolled by 51 sites. Patients were mostly male (61.2%) with a mean age of 58.5 (±12.0) years; 1.7% were BRAF mutated; 420 patients were treated with FOLFIRI-based regimens and 94 with FOLFOX. The most common primary tumor site was rectum (38.8%) with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%-49.7%), including 26 patients (5.0%) with a complete response. Median progression-free survival was 9.9 months (95% CI, 8.2-11.0); median overall survival (mOS) was 30.8 months (95% CI, 27.9-33.6). Patients receiving FOLFIRI-based regimens had better outcomes than those on FOLFOX, including increased ORR (48.6% vs 34.0%) and mOS (31.3 vs 28.6 months). Higher mOS was also associated with tumors of left- rather than right-sided origin (HR 0.69 [95% CI, 0.49-0.99]), and higher ORR with liver metastases compared to all other metastases (55.4% vs 40.2%). Adverse events were consistent with the known safety profile of cetuximab. The most common treatment-related adverse events (TRAE) were rash (20.2%), dermatitis acneiform (16.5%), and paronychia (13.7%); 2.1% of patients had a serious TRAE.

Conclusions

Cetuximab-based 5-FU regimens were effective in treating patients with mCRC, particuarly in those with left-sided disease origin and with liver metastases only, in routine practice. FOLFIRI-based cetuximab regimens were more common and showed improved outcomes over FOLFOX. Our findings are consistent with recent studies.

Editorial acknowledgement

Medical editorial asssistance provided by Kristen Perry and Tim Stentiford, CMPP, of ClinicalThinking, part of Nucleus Global, and was funded by Merck Pte. Ltd.

Legal entity responsible for the study

Merck Pte. Ltd.

Funding

Merck Pte. Ltd.

Disclosure

T.W. Kim: Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Sanofi. J.B. Ahn: Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Boryung. G.F. Ho: Honoraria (self): Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Tessa Therapeutics; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: AstraZeneca; Full/Part-time employment: University Malaya Medical Centre; Full/Part-time employment: UM Specialist Centre. L.T. Anh: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck KGaA; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis. S. Temraz: Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck KGaA; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD. M. Burge: Advisory/Consultancy: Merck KGaA. C. Chua: Research grant/Funding (institution): MSD; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Merck KGaA. J. Huang: Full/Part-time employment: Merck Pte Ltd. Y.S. Park: Advisory/Consultancy: Merck KGaA; Full/Part-time employment: Samsung Medical Center. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

106P - Efficacy and tolerability of capecitabine and mitomycin-C based concurrent radiotherapy in patients with anal canal cancer (ID 782)

Presentation Number
106P
Lecture Time
09:00 - 09:00
Speakers
  • Prabhat G. Bhargava (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Stage I-III squamous cell cancers (SCC) of the anal canal are treated with definitive concurrent chemoradiotherapy. Capecitabine (Cape) and mitomycin-C (MMC) chemotherapy is an approved concurrent regimen, but with limited evidence.

Methods

A retrospective analysis of stage I-III SCC patients treated at Tata Memorial hospital with concurrent Cape-MMC (Capecitabine 1250mg/m2 PO continuous with IV Mitomycin C 12mg/m2 on D1) based chemoradiotherapy from March 2014 to March 2020 was conducted. Patients were staged as per American Joint Committee on Cancer, seventh edition. The primary outcome of the study was recurrence-free survival (RFS). Overall survival (OS) and RFS were calculated by Kaplan-Meier estimates.

Results

Two hundred and twenty-six patients were included in the study, with the median age being 58 (range: 22-81) years. Stage I, stage II, and stage III cancers were seen in 1(0.4%), 62 (27.4%), and 163 (72.1%) patients, respectively. Patients received a median 45 Gy (range; 20-63) in 25 fractions as definitive radiotherapy with concurrent Cape-MMC. Response evaluation at 6 months was available in 190 patients, with 51 patients (27%) having local residual or progressive disease. Nine patients (4%) underwent salvage surgery. At a median follow up of 28 months, 38 recurrences had occurred, with 13 patients having only local recurrence while 25 patients had distant metastasis, with or without local recurrences. The median 2-year RFS was 82%, while median 2 years OS was 85%. Patients with stage III disease had inferior RFS as compared to patients with stage I/II disease (2 year RFS: 78% vs. 90%; p=0.042) Common grade 3 and grade 4 toxicities were local skin reactions in 44 (21.4%), neutropenia and thrombocytopenia in 9 (4.4%) patients, respectively.

Conclusions

The current study using chemoradiation with Cape-MMC is a large study in predominantly stage III anal canal cancers and shows excellent loco-regional control rates and tolerance in comparison to the traditional 5 fluorouracil-based regimens.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

107P - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in previously treated metastatic colorectal cancer (mCRC): Results from the Australian cohort of the phase IIIb, international, open-label, early-access PRECONNECT study (ID 291)

Presentation Number
107P
Lecture Time
09:00 - 09:00
Speakers
  • Timothy J. Price (Woodville, SA, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The PRECONNECT study assessed safety and efficacy of FTD/TPI in previously treated mCRC patients in daily practice. This analysis presents the results from the Australian patient cohort.

Methods

Enrolled patients had confirmed mCRC and ECOG PS of 0 or 1, previously treated with, or not considered candidates for available therapies. Patients received FTD/TPI (35 mg/m2, orally bid, on days 1–5 and 8–12 in a 28-day cycle) with follow-up to the end of study treatment. Withdrawal criteria included disease progression, unacceptable toxicity and commercial availability of FTD/TPI. The primary endpoint was safety; secondary endpoints were PFS and QoL.

Results

70 Australian patients from 9 centres received at least one dose at cut-off (May 2018). At baseline, median age was 61 years (range 27–77); 57.1% male; 80% Caucasian, 14.3% Asian, 1.4% Black. ECOG PS was 0/1 in 54%/44%. 60% had RAS-mutant cancers; 10% had BRAF-(V600E) mutant cancers. Primaries were left-sided in 71%, right-sided in 14% (14% not specified). Over 98% received prior fluoropyrimidine and/or oxaliplatin, irinotecan, while 91%, 36% and 0% received anti-VEGF, anti-EGFR or regorafenib respectively. Most common any-grade treatment-emergent adverse events (TEAs) were nausea (49%), asthenia/fatigue (40%), neutropenia (34%), vomiting (33%), diarrhoea (26%), Anemia (21%) and constipation (20%). Most common TEAs grade ≥3 were: neutropenia (31%), anaemia (10%), diarrhoea, nausea, vomiting, abdominal pain (3%). TEAs led to patient withdrawal in 7% and dosage reduction in 9%. Median treatment duration was 3 cycles (range 1–16). Median relative dose intensity was 92%. FTD/TPI was associated with a median PFS of 2.7 months (95% CI, 2.4–3.4) and disease control rate of 40% (95% CI, 28.47–52.41). Median time to ECOG PS decline to ³2 was 14 months. Mean QLQC30 GHS at baseline was 67.2 (±17.8) with mean change from baseline to end of therapy of -11.3 (±21.7) points.

Conclusions

Results from the Australian cohort are consistent with the global PRECONNECT population and randomised datasets in previously treated mCRC patients.

Clinical trial identification

NCT03306394.

Legal entity responsible for the study

Institut de Recherches Internationales Servier.

Funding

Institut de Recherches Internationales Servier.

Disclosure

G. Tancock: Full/Part-time employment: Servier Australia Pty. Ltd. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

108P - Comparative analysis of two-stage hepatectomy and enhanced one-stage hepatectomy in the setting of bilobar colorectal liver metastases (ID 756)

Presentation Number
108P
Lecture Time
09:00 - 09:00
Speakers
  • Hayk G. Torgomyan (Nizhny Novgorod, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Multiple bilobar colorectal liver metastases (CLM) is a big challenge for surgeon oncologist due to high risk of postoperative morbidity and mortality. Two-stage hepatectomy (TSH) is a nowadays surgical standard. As alternative enhanced one-stage hepatectomy (e-OSH) with intraoperative ultrasound control to reduce the resection of the unaffected parenchyma could be performed.

Methods

665 patients with CLM who underwent liver resection at the Privolzhsky District Medical Center from 2010 to 2017 were retrospectively analyzed. Inclusion criteria were multiple CLM in one lobe with at least one lesion in the contralateral lobe. 76 patients (11,5%) were included in the study: 49 with TSH and 27 with e-OSH. Post-operative complications rate and overall survival in 2 groups were investigated and compared.

Results

Among 49 patients in first group (TSH) 23 reached to the second stage. Drop-out rate of TSH was 53%. Compared to the e-OSH patients who reached to the second stage had similar overall morbidity (TSH – 30.4% vs. e-OSH – 33.3% p = 0.827), liver-specific morbidity (TSH – 17.4% vs. e-OSH – 29.6%, p = 0.313) severe morbidity (TSH – 21.7% vs. e-OSH – 22.2% p = 0.968) and overall mortality (TSH – 8,7% vs. e-OSH – 14,8% p = 0.507). R0 resection rate was similar between groups. Completed TSH and e-OSH had similar overall survival rate (1-year 83% vs. 73% р = 0.313; 3-year 39% vs. 38% р = 0.880).

Conclusions

e-OSH may be considered as the surgical treatment of choice due to the absence of drop-out risk and a similar to TSH rate of morbidity, mortality, and overall survival. TSH is preferable to perform in cases where postoperative fatal liver insufficiency is highly likely.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

109P - Efficacy and safety of biweekly or triweekly XELOX regimen for adjuvant chemotherapy of colorectal cancer (ID 632)

Presentation Number
109P
Lecture Time
09:00 - 09:00
Speakers
  • Hangyu Zhang (hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Adjuvant CAPOX (capecitabine plus oxaliplatin) provided significant disease-free survival (DFS) benefit in patients with high-risk stage Ⅱor stage Ⅲ colorectal cancer (CRC), which might translate into long-term overall survival (OS). However, the standard triweekly CAPOX has recently raised some concerns onits hematological toxicity such as thrombocytopenia, which results in discontinuation ofadjuvant courses in a majority of patients. The regimen of modified biweekly CAPOX was observed to be generally well-tolerated in previous studies.

Methods

We conducted a prospective, phase II study to investigate the efficacy and safety between these two adjuvant chemotherapy models. Patients were randomized (1:1) to receive capecitabine 1000mg/m2 BID D1-D14 with oxaliplatin 130mg/m2 IV D1, Q21 days(standard triweekly arm) or capecitabine 1000mg/m2 BID D1-D10 with oxaliplatin 85mg/m2 IV D1, Q14 days (modifiedbiweeklyarm) as adjuvant therapy. Patients with T3N1M0 disease would receive 3 months of adjuvant chemotherapy while patients who had T4 or N2 disease would receive 6 months of adjuvant chemotherapy. The primary endpoint was DFSwhile safety and OS were secondary endpoints.

Results

Since the enrollment of the first patient on June 28, 2018, 85 patients have been enrolled, 59 of whom have completely completed adjuvant therapy, 20 patients are still in treatment, and 6 patients terminated the treatment due to personal reasons, adverse reactions intolerant or postoperative complications such as intestinal adhesion. Of the 59 patients who completed adjuvant therapy, 29 received the triweekly regimen and 30 received the biweekly regimen, respectively. Leukopenia was 43% in the biweekly group and 58% in the triweekly group. Thrombocytopenia was 33% at biweekly group, 51% at triweekly group. Peripheral neurotoxicity was 46% at biweekly group, and 75% at triweekly group.

Adverse events Grade Case No.
Biweekly XELOX Triweekly XELOX
WBC I 9 6
II 3 43% 10 58%
III 1 1
PLT I 4 7
II 3 33% 6 51%
III 3 2
Hb I 9. 36% 5 20%
II 2 1
Liver function injury I 2. 16% 5 31%
II 3 4
Peripheral neurotoxicity I 7 10
II 3 46% 5 75%
III 4 7

Conclusions

Blood toxicity was significantly reduced in the biweekly treatment group, as were liver function injury and neurotoxicity.DFS and OS are not available for the time being due to immature data.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

110P - Analysis for stereotactic body radiotherapy (SBRT) effect for colorectal liver metastases (ID 726)

Presentation Number
110P
Lecture Time
09:00 - 09:00
Speakers
  • Wei Zou (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There are various treatment methods for colorectal metastasis, such as surgery and RFA. However, not every patient is suitable for surgery, and radiofrequency ablation is a better for lesions less than 3 cm in diameter. Under this situation, SBRT can be a choice, which has the advantages of non-invasiveness and high precision. So far, there are relatively few studies on SBRT of colorectal liver metastasis worldwide and no studies have been reported in China. Therefore, this study retrospectively analyzes patients receiving SBRT treatment of colorectal liver metastasis, to explore its effectiveness and safety.

Methods

We retrospectively analyzed CRLM patients who received SBRT treatment for liver metastases from 2017 to 2019 in our center. 20 liver lesions in total were treated. Most patients (91.7%) previously received other local treatment, and Most (91.7%) patients received first-line and above systemic treatment. The median size of treated lesions is 2.5cm(1.2∼2.5cm). The average dose was 49Gy(48∼64Gy), with average fraction number of 7(5∼10) times, equals to BED as 85.5Gy(72∼115.2Gy).

Results

The median follow-up time was 15 months (range 3-22 months). 4 lesions were observed recurrence in the irradiation field. The 6-month, 1-year local control rate was 94% and 75%, if evaluated by lesion. By univariate analysis, the local control rate of liver metastases with a maximum diameter <3 cm was significantly better than that of lesions ≥ 3 cm. The 1-year local control rate was 82% and 33%, respectively, P=0.016. The patients had a median PFS of 8 months, 6 months of PFS of 58%, and 1 year of PFS of 10%. The median OS was not reached. The 6-month OS was 92%, and the 1-year OS was 73%. None of the patients had toxicity ≥ higer grade 3.

Conclusions

SBRT treatment for liver metastases from rectal cancer has shown promising local control and survival outcomes. And the local control rate of liver metastases < 3 cm in diameter was better than that of lesions ≥ 3 cm.

Legal entity responsible for the study

Fudan University Cancer Center, Shanghai, China.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

111P - A meta-analysis study on safety and effectiveness comparison between FOLFOX and XELOX regiments on advanced stage colorectal cancer (ID 871)

Presentation Number
111P
Lecture Time
09:00 - 09:00
Speakers
  • Ida Bagus Budhi (Surakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Advanced stage colorectal cancer therapy shows positive progress by increasing overall survival (OS). Mainstay treatment still uses cytotoxic agents and oxaliplatin which results in an average survival of 18 months when combined with 5-Fluorouracil (5-FU) or capecitabine. This study aims to determine the effectiveness and safety of the use of FOLFOX and XELOX chemotherapy in advanced stage colorectal cancer patients using a meta-analysis study.

Methods

This is a meta-analysis study comparing only the Randomized Controlled Trial (RCT) study using FOLFOX and XELOX chemotherapy in patients with metastatic colorectal cancer taken from PubMed, EMBASE and The Cochrane Library using keywords: Capecitabine, FOLFOX, XELOX and metastatic colorectal.

Results

9 journals were included in the inclusion criteria and were followed by a meta-analysis study. A total of 5,873 patients were obtained with the number of groups given FOLFOX of 3,034 and 2,839 in the group given XELOX. The analysis doesn’t show evidence of publication bias in the forest plot. The results of the analysis of Progress Free Survival (PFS) found no significant heterogeneity (OR = 1.09, 95% CI: 0.97-1.23, p = 0.14), the Overall Survival (OS) analysis also did not obtain heterogeneity (OR = 0.98, 95% CI : 0.87-1.10, p = 0.77). Overall Response Rate (ORR) there were no significant differences in the two groups. All studies gave grade 3 and 4 toxicity. The results of the combined analysis showed thrombocytopenia, Hand Foot Syndrome (HFS) and diarrhea in the XELOX group were significantly higher.

Conclusions

The effectiveness of XELOX and FOLFOX found no significant differences. However, the safety of the XELOX group showed significantly more side effects. Keywords: FOLFOX, XELOX, Advanced Stage Colorectal Cancer.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 89) Poster Display

112P - Pembrolizumab vs chemotherapy in patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: Asia subgroup results of the phase III KEYNOTE-177 study (ID 1048)

Presentation Number
112P
Lecture Time
09:00 - 09:00
Speakers
  • Takayuki Yoshino (Kashiwa, Chiba, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
22.11.2020
Time
09:00 - 20:00

Abstract

Background

KEYNOTE-177 (NCT02563002) was a randomized, open-label phase III study of first-line (1L) pembrolizumab (P) vs chemotherapy (C) in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). P significantly improved progression-free survival (PFS) vs C in KEYNOTE-177; the Asia subgroup (sg) analysis is presented.

Methods

Pts with previously untreated dMMR/MSI-H stage IV mCRC and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned 1:1 to P 200 mg every 3 weeks or investigator’s choice of C (mFOLFOX6/FOLFIRI every 2 weeks ± bevacizumab/cetuximab). Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 by central review and overall survival. Hazard ratio and 95% confidence interval of PFS were based on Cox regression model with Efron’s method of tie handling with treatment as a covariate. PFS and duration of response (DOR) were assessed per Kaplan-Meier analysis. Secondary endpoints were overall response rate (ORR) and safety. Confirmed responses are shown.

Results

Of 307 pts enrolled in the study, 153 were randomly assigned to P and 154 to C. Of the 307 pts, 48 were enrolled from Asia (P, n=22; C, n=26). At data cutoff (19 Feb 2020), median follow-up in the Asia sg was 28.7 mo in the P arm vs 23.3 mo in the C arm. Efficacy and safety in the total population (pop) and Asia sg are presented in the table.

Conclusions

1L P compared with C showed clinically meaningful improvement in PFS, led to more durable responses and improved safety profile in the total pop of pts with dMMR/MSI-H mCRC. The Asia sg results were generally consistent with those of the total pop of KEYNOTE-177

P (total pop) C (total pop) P (Asia sg) C (Asia sg)
ITT pop, n 153 154 22 26
Median PFS, mo 16.5 8.2 NR 10.4
HR (95% CI) 0.60 (0.45-0.80) -- 0.65 (0.30-1.41) --
12-mo PFS rate, % 55.3 37.3 62.0 45.9
ORR, n (%) 67 (43.8) 51 (33.1) 10 (45.5) 12 (46.2)
CR, n (%) 17 (11.1) 6 (3.9) 2 (9.1) 3 (11.5)
PR, n (%) 50 (32.7) 45 (29.2) 8 (36.4) 9 (34.6)
Median DOR, (range), mo NR (2.3+-41.4+) 10.6 (2.8-37.5+) NR (4.4+-33.1+) 28.8 (3.4+-35.5+)
Response duration ≥24 mo, % 82.6 35.3 87.5 51.1
APAT pop, n 153 143 22 25
Any grade TRAE, n (%) 122 (79.7) 141 (98.6) 14 (63.6) 25 (100.0)
Grade 3-5 TRAE, n (%) 33 (21.6) 94 (65.7) 2 (9.1) 20 (80.0)

APAT, all patients as treated; NR, not reached; TRAE, treatment-related adverse event.

.

Clinical trial identification

NCT02563002.

Editorial acknowledgement

Provided by Jemimah Walker, PhD, and Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. Yoshino: Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Amgen K.K., Parexel International Inc., MSD K.K., Daiichi Sankyo Co., Ltd., and Sanofi K.K. T.W. Kim: Research grant/Funding (institution): Research Grant/Funding (Institution) Merk Serono, AstraZeneca, Pfizer. W.P. Yong: Speaker Bureau/Expert testimony: Bayer. K-K. Shiu: Honoraria (self): BMS, Guardant Health, Innovent Biologics, Merck KGaA, Roche, Servier; Advisory/Consultancy: Roche; Research grant/Funding (institution): Amgen, BMS, Gilead, Merck KGaA, MSD, Roche; Travel/Accommodation/Expenses: MSD, Merck KGaA, Innovent Biologics. B. Vittrup Jensen: Research grant/Funding (institution): Merck Sharp & Dohme Corp. L. Henrik Jensen: Research grant/Funding (institution): MSD, 2cureX, Incyte, BMS. R. Garcia-Carbonero: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Research grant/Funding (self): Pfizer, BMS; Research grant/Funding (institution): ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Non-remunerated activity/ies: Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), Member of the Scientific Advisory Group for Oncology (SAG-O) of th; Non-remunerated activity/ies: Global PI of a clinical trial of Axitinib (Pfizer) in NETs; Global PI of a clinical trial of Nivolumab (BMS) and chemotherapy in NECs; Non-remunerated activity/ies: Member of the EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD. J. Alcaide-Garcia: Speaker Bureau/Expert testimony: Amgen; Travel/Accommodation/Expenses: MSD, Merck, Roche, Sanofi, Bristol. P. Gibbs: Honoraria (self), Research grant/Funding (self): Merck. C. de la Fouchardiere: Advisory/Consultancy: Roche, Pierre Fabre Oncologie, MSD, Eisai, Bayer; Travel/Accommodation/Expenses: Amgen, Eisai, BMS, Roche. F. Rivera: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene. E. Elez: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, Servier, MSD, Array Pharmaceuticals, Bristol-Myers Squibb; Honoraria (institution): Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Array Pharmaceuticals, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune. J. Bendell: Research grant/Funding (institution): Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Koltan, SynDevRex, Forty Seven, AbbVie, Ar; Advisory/Consultancy: Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Array, Sanofi, ARMO, Ipsen, Merrimack, Oncogenex, FORM; Travel/Accommodation/Expenses: Gilead, Genentech/Roche, BMS, Lilly, Merck, MedImmune, Celgene, Taiho, Novartis, OncoMed, BI, ARMO, Ipsen, Oncogenex, FORMA. D.T. Le: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Aduro, Medivir, Curegenix, Nouscom; Licensing/Royalties: Patent pending: technology for mismatch repair deficiency. P. Yang: Full/Part-time employment: MSD China Holding Co., Ltd.. M. Farooqui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. P. Marinello: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. L.A. Diaz: Advisory/Consultancy: Personal Genome Diagnostics, 4Paws, Neophore; Leadership role: Jounce Therapeutics, Personal Genome Diagnostics; Shareholder/Stockholder/Stock options: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Amgen, Thrive; Research grant/Funding (self), Non-remunerated activity/ies: Merck; Travel/Accommodation/Expenses: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Merck, Neophore; Licensing/Royalties: Personal Genome Diagnostics, Thrive, Qiagen; Officer/Board of Directors: Jounce Therapeutics, Personal Genome Diagnostics. T. Andre: Honoraria (self): Bristol-Myers Squibb, Chugai, GSK, Pierre Fabre, Roche/Vantana, Sanofi, Servier ; Advisory/Consultancy: Amgen, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Gritstone Oncology, Halliodx, Merck Sharp & Dohme Corp, Pierre Fabre, Roche/Vantana, Sanofi, Servier, Tesaro; Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Servier; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Travel/Accommodation/Expenses: Roche/Vantana, Merck Sharp & Dohme Corp, Bristol-Myers Squibb; Non-remunerated activity/ies: Participant to the Scientific committee of ARCAD Foundation and GERCOR Group. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

113TiP - Prospective observational study monitoring circulating tumour DNA in resectable colorectal cancer patients undergoing radical surgery: GALAXY study in CIRCULATE-Japan (ID 328)

Presentation Number
113TiP
Lecture Time
09:00 - 09:00
Speakers
  • Hiroki Yukami (Kashiwa, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Adjuvant chemotherapy has reduced the risk of recurrence and improved survival in patients with resected colorectal cancer (CRC). Early clinical utility of circulating tumor DNA (ctDNA) pre- and post-surgery has been reported across various solid tumor subtypes including CRC. Analysis of ctDNA status can be utilized as a predictor biomarker for stratifying patients based on their risk of recurrence and to monitor the effectiveness of adjuvant chemotherapy.

Trial design

GALAXY is a prospective observational study to monitor the ctDNA status and to establish the registry data in patients with stage II-IV CRC who will undergo a radical surgery. The study utilizes a personalized, tumor-informed ctDNA assay (Signatera™ bespoke multiplex-PCR NGS assay) that tracks patient-specific somatic single nucleotide variants present in plasma based on the whole-exome sequencing of tumor tissue. A total of 2500 patients will be enrolled at 146 sites and will be followed-up for 7 years. Blood samples will be collected at pre-surgery and post-surgery at 1, 3, 6, 9, 12, 18, and 24 months. Patients will also undergo regular radiologic assessment at pre-specified timepoints. Mutations in RAS, BRAF and microsatellite instability will be analyzed using PCR. The primary endpoint of the study is disease-free survival and secondary endpoints are overall survival, analysis of ctDNA status at each time point, and association between clinical characteristic and genetic alterations. Based on the ctDNA results in the GALAXY trial, patients can be enrolled either of the two distinct investigator-initiated phase III trials: the VEGA trial (treatment de-escalation) or the ALTAIR trial (treatment escalation). The VEGA trial assesses the non-inferiority of observation vs. adjuvant CAPOX in GALAXY participants who are high-risk stage II or low risk stage III CRC and show absence of ctDNA one-month post-surgery. The ALTAIR trial evaluates the superiority of FTD/TPI over placebo in GALAXY participants with ctDNA status that remains positive after the standard therapy. Moreover, additional tumor tissue and blood samples will also be banked for multi-omics analysis.

Clinical trial identification

UMIN000039205 on 01/20/2020.

Legal entity responsible for the study

CIRCULATE-Japan.

Funding

This study is funded by Japan Agency for Medical Research and Development (AMED).Grant number: JP19ck0106447.

Disclosure

D. Kotani: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Lilly; Honoraria (self): Merck Biopharma; Honoraria (self): Taiho; Honoraria (self): Sysmex. E. Oki: Speaker Bureau/Expert testimony: Bayer Yakuhin; Speaker Bureau/Expert testimony: Chugai Pharmaceutical Co., Ltd; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co., Ltd.; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Yakult Honsha Co., Ltd.; Speaker Bureau/Expert testimony: Merck Serono; Speaker Bureau/Expert testimony: Takeda Pharmaceutical Co., Ltd. H. Taniguchi: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Taiho. Y. Nakamura: Research grant/Funding (self): Ono; Research grant/Funding (self): Taiho. T. Kato: Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Takeda Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Bayer Yakuhin Ltd.; Honoraria (self): Sanofi K.K.; Honoraria (self): Yakult Honsha Co. Ltd. T. Yamanaka: Honoraria (self), Research grant/Funding (self): Takeda Pharma; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Taiho Pharma; Honoraria (self), Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (self): Ono Pharma; Research grant/Funding (self): Merck Biopharma; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): Bayer. A. Aleshin, P. Billings: Full/Part-time employment: Natera Inc. T. Yoshino: Research grant/Funding (self): Novartis Pharma K.K; Research grant/Funding (self): MSD. K.K.; Research grant/Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (self): Sanofi K.K.; Research grant/Funding (self): Daiichi Sankyo Company, Limited; Research grant/Funding (self): Parexel International Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (self): GlaxoSmithKline K.K.. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO7 - Locally Advanced Rectal Cancer- A Case Report (ID 340)

Presentation Number
YO7
Lecture Time
09:00 - 09:00
Speakers
  • Uthaman Jithin (Chongqing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

Gastrointestinal tumours, non-colorectal (ID 1146)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

122P - Nomogram to predict short-term effect of radiotherapy based on pre/post-treatment inflammatory biomarkers and their dynamic changes in esophageal squamous cell carcinoma (ID 271)

Presentation Number
122P
Lecture Time
09:00 - 09:00
Speakers
  • Shuai Liang (Jinan, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

We initial aimed to investigate pre/post-treatment inflammatory biomarkers (pre/post-IBs) and their dynamic changes (delta-IBs) on short-term effect (STE). Furthermore, a nomogram was built to provide accurate prediction of STE in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy.

Methods

The IBs included absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). All pre/post-IBs and delta-IBs of 398 ESCC patients at Shandong Cancer Hospital between 2015 and 2019 were analyzed. The nomogram was then constructed that forecasted STE based on logistic regression analyses.

Results

At 1 month after radiotherapy, 261 patients (65.6%) achieved remission, and 137 patients (34.4%) achieved un-remission. The pre-ALC and pre-LMR significantly increased, pre-NLR and pre-PLR significantly decreased during radiotherapy (all P<0.001). Meanwhile, there was a positive correlation between delta-NLR as well as delta-PLR and delta-LMR (r=0.621 and 0.613, respectively), whereas a negatively correlated between delta-LMR and delta-PLR (r=-0.573). Multivariate analysis indicated that gender [OR, 0.473; 95%CI, 0.274-0.816; P=0.007], pre-ALC [OR, 0.554; 95%CI, 0.335-0.915; P=0.021], pre-NLR [OR, 3.176; 95%CI, 1.733-5.823; P<0.001], post-NLR [OR, 2.418; 95%CI, 1.271-4.600; P=0.007] and delta-NLR [OR, 1.929; 95%CI, 1.035-3.595; P=0.039] were statistically significant with STE. Nomogram for STE was established by combining all independent predictors and the concordance indexes for STE were 0.770 [95%CI, 0.719–0.820].

Conclusions

In conclusion, pre-NLR and pre-ALC, post-NLR, and delta-NLR could predict STE in ESCC patients. Further, pre-NLR had the best predictive value, and the developed nomogram with superior prediction ability for STE could assist in patients counseling and guide to make treatment decisions.

Legal entity responsible for the study

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan 250117, Shandong, People’s Republic of China.

Funding

This work was supported by the National Natural Science Foundation of China (81972864), Academic Promotion Program of Shandong First Medical University (2019RC002), Science and Technology Support Plan for Youth Innovation Teams of Universities in Shandong Province (2019KJL001) and Science and Technology Plan of Jinan (201907113).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

123P - The clinical value of prognostic nutritional index in esophagogastric junctional adenocarcinoma patients with anastomotic leakage after surgery (ID 149)

Presentation Number
123P
Lecture Time
09:00 - 09:00
Speakers
  • Yan Wang (Shijiazhuang, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To study the relationship between prognostic nutritional index (PNI) and clinicopathological factors in gastroesophageal junction cancer patients with postoperative anastomotic leakage and the clinical significance of PNI in predicting the survival of patients with postoperative anastomotic leakage.

Methods

Clinicopathological and follow-up data of 115 gastroesophageal junction cancer patients with anastomotic leakage after radical surgery in the Department of Thoracic Surgery, the 4th Hospital of Hebei Medical University from January 1 2004 to December 31 2013 were retrospectively analyzed. PNI values were calculated [PNI = absolute lymphocyte count (109/L) x 5 + serum albumin (g/L)], and was grouped according to the PNI mean value. Relationships of PNI with patient gender, age, tumor stage, tumor differentiation, tumor location, lymph node metastasis were analyzed. For survival analysis, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis.

Results

The mean PNI of patients with anastomotic leakage was 48.51 (43.25∼56.25). The 5-year survival rate of patients with PNI ≤48.51 was 58.9%, and the 5-year survival rate for patients with PNI>48.51 was 59.3%. There was no significant difference between the two groups (χ2=0.127, P=0.722). Univariate and multivariate analysis showed that N stage is an independent risk factor for the prognosis of patients with PNI≤48.51. Postoperative adjuvant treatment is an independent risk factor for the survival of patients with PNI>48.51. P for interaction between PNI and treatment modality: P=0.037.

Conclusions

The independent prognostic factors of patients with esophagogastric junction adenocarcinoma combined with anastomotic leakage are N stage and adjuvant treatment for PNI≤48.51 and PNI>48.51 group, respectively. For patients with esophagogastric junction adenocarcinoma combined with anastomotic leakage, PNI is an important factor for guiding the selection of appropriate postoperative treatment.

Legal entity responsible for the study

The Fourth Hospital of Hebei Medical University.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

124P - Prospective evaluation of pattern of care and quality of life in patients undergoing esophagectomy at a high-volume regional cancer centre in South India (ID 249)

Presentation Number
124P
Lecture Time
09:00 - 09:00
Speakers
  • Faheem A. Abdulla (Thiruvananthapuram, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Carcinoma esophagus is a disease with dismal prognosis and even though treatment has evolved considerably, morbidity after surgery has remained a drawback. We intend to prospectively study the pattern of care for such patients at our centre, how it affects their subsequent quality of life (QoL) and the factors that influence these changes.

Methods

All patients who underwent curative esophagectomy for carcinoma esophagus from May,2017 to May,2019 were included in the study after obtaining informed consent. Patient characteristics, pre-op therapy, surgical details and final histopathology reports were collected. QoL was collected at pre-op, 1 and 6 months after surgery using FACT-E, OES 18 and OG 25 questionnaires. QoL analysis was done comparing the changes that occured after curative surgery with the baseline value.

Results

99 patients underwent curative esophagectomy during the study period. With a mean age of 58.8 and a male to female ratio of 3.54 : 1, 84/99 underwent surgery after NACT. Lower third and GE junction primary adenocarcinomas accounted for 72 % of cases. Totally minimally invasive McKeowns procedure was the most common surgery done (33%). 8 patients comprised the 30-day mortality with 5 patients having anastomotic leak. QoL analysis showed a dip in post-op QoL at 1 month, with improvement to baseline at 6 months, both in general functional scales, as well as symptom scales. The improvement in symptom scales assessed by OES 18 and OG 25 were found to be statistically significant ( p value < 0.05). Younger patients (<50 yrs) and females fared better during the post-op period. There was a trend to better QoL for patients who underwent minimally invasive procedures. Those patients who had post-op complications, had inferior QoL at 1 month, but later improved by 6 months.

Conclusions

Radical esophagectomy can be performed with achievable morbidity and mortality at high volume centres. Global HRQoL scores show a dip during immediate post-surgery period, but then picks up to even eclipse pre-op values. Post-op morbidity, as expected, adversely affects HRQoL, but once patients tide over the immediate period, they often do well as time passes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

125P - Analysis of esophageal cancer incidence for last 20 years in Uzbekistan (ID 829)

Presentation Number
125P
Lecture Time
09:00 - 09:00
Speakers
  • Abrorjon A. Yusupbekov (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Esophageal cancer (EC) takes, all over the world, 9th place in the structure of new incidents of malignant tumors, amounting to 572034 registered cases and 6th place in the structure of mortality rate, taking 508585 lives annually. According to statistical data, EC develops much more often in men than in women (70% of new cases have developed in men), and people over 70 make up about 40% of the total number of cases, with a peak incidence occurring at the age of 50-60 years. However, these indicators vary by geographic region. So, for example, the highest incidence is found in East Asia, eastern and southern Africa (8.1-23.6‱), while the lowest rate belongs to central America. The aim of the research was to study the dynamics of changes in the incidence trends in the Republic of Uzbekistan over the past 20 years.

Methods

A meta-analysis of the detection of mortality of esophageal cancer (EC) for all patients with the verified diagnosis was performed. For the period from 2000 - 2019, 18129 patients were identified in the Uzbekistan and the average incidence of EC was 2.8 per 100 thousand of the population. Of these 8283 (45.7%) were treated at the clinic of NCC, in particular, 1174 (14.2%) patients were operated.

Results

The analysis revealed that in 2000, in 0,4% and 18,2% of cases, patients had I - II stage disease, in 64,5% of cases – III, and in 18,2% of cases – IV clinical stage, in 2009, 0,5% and 22,8% of cases, patients had I - II stage disease, in 54,4% of cases – III, and in 16,4% of cases - IV clinical stage, and in 2019, 3,3% and 33,7% of cases patients had I – II stage disease, in 44,5% of cases - III, and in 12,5% of cases - IV clinical stage.

Conclusions

A relative decrease in the mortality rate over the study period was also revealed: from 2.7% in 2000 to 1.8% in 2019. There has been a decrease in the mortality trend - 2000, 2009 and 2019, 2.2, 1.7 and 1.1, respectively. At the same time, 5-year survival was relatively stable and varied in the range of 12.1% - 27.3%. The largest number of patients was identified in the clinical stage III of the disease and ranged from 42.2 to 67%, respectively.

Legal entity responsible for the study

Republican Specialized Oncology and Radiology Research - Practice Medical Center (National Cancer Center).

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

126P - A phase II study of rh-endostatin combined with irinotecan plus cisplatin as the second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) (ID 604)

Presentation Number
126P
Lecture Time
09:00 - 09:00
Speakers
  • Jianhua Chang (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For patients (pts) with advanced ESCC, there is lack of effective treatment. Rh-endostatin (endostar) has shown clinical activity when combined with chemoradiotherapy in treating locally advanced ESCC. This single-arm phase II study aimed to assess the efficacy and safety of endostar combined with irinotecan and cisplatin as the second-line treatment for pts with advanced ESCC.

Methods

Eligible pts were histologically proven stage IV ESCC; 18-75 years old; had progressive disease after first line treatment or chemoradiation within a year; at least one measureable lesion according to RECIST 1.1; ECOG PS 0-1. Endostar (15 mg/m2/day, continuous infusion, day 1-7) plus irinotecan (60 mg/m2, day 1, 8) and cisplatin (60 mg/m2, day 1) were administered every 3 weeks for 4-6 cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Results

From May 2017 to Jun 2020, 52 pts were enrolled and 1 patient withdrawn consent before receiving treatment, 1 patient was excluded due to concurrent radiotherapy. The mean cycle of treatment was 3.4 (range 1 to 6) in 46 patients with study discontinuation, while 4 patients remain receiving investigational treatment. Among these patients, 46 pts (90.2%) were male, and the median age was 60 (47-73). 47 pts were assessable for response. A total of 13 pts achieved partial response and 18 pts had stable disease. ORR was 27.7% and DCR was 66.0%. To date, 42 PFS events and 22 OS events have occurred. The median PFS and OS were 3.8 months (95% CI 2.4-5.3 months) and 12.3 months (95% CI 7.0-17.6 months), respectively. The most common AEs observed during this study were anemia (35.3%), neutropenia (29.4%), abdominal distension (29.4%), fatigue (27.5%), anorexia (19.6%). The most common Grade 3/4 AEs observed were neutropenia (15.7) and diarrhea (9.8%).

Conclusions

The combination of endostar plus irinotecan and cisplatin is a well-tolerated treatment option with promising activity in the second line treatment of advanced ESCC. Its efficacy and safety profile warranted further study in randomized trials.

Clinical trial identification

NCT03797625.

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

127P - A prospective phase II clinical trial exploring neoadjuvant immunotherapy combined with chemotherapy in resectable thoracic esophageal squamous cell cancer (TESCC) with multi-station lymph node metastases (NICE study): Preliminary results (ID 549)

Presentation Number
127P
Lecture Time
09:00 - 09:00
Speakers
  • Jun Liu (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients (pts) with resectable TESCC with multi-station lymph node metastases derive unoptimistic overall survival benefit with neoadjuvant or postoperative adjuvant therapy. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced TESCC in China. We hypothesize that the addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) will increase the pathological complete response (pCR) rate compared with historical controls.

Methods

This was an investigator-initiated trial for pts with newly diagnosed AJCC 8th resectable TESCC with multi-station lymph node metastases with a plan to have surgery. Pts received 2 courses of camrelizumab 200mg IV q3w added to carboplatin AUC=5 IV q3w plus albumin paclitaxel 100 mg/m2 IV qwk with surgery 4 wks after the last dose. The primary objective was pCR. Our primary endpoint will be reached if 5/52 (9.6%) planned pts have pCR.

Results

From 11/2019 to 6/2020, 11 pts were enrolled all of whom had surgery. Median age was 65 (55-72), 9.1% women, and 36.4% PD-L1 positive (≥1%, 22C3). Pre-surgical grade 3/4 toxicity occurred in 8/11pts, and treatment was delayed by an average of 5.7 days due to toxicities. Grade 3/4 toxicities were neutropenia (8/11), thrombocytopenia (2/11). All pts recovered well from pre-surgical toxicities.Our primary endpoint was met; the pCR (pT0N0M0) was achieved in 45.4% (5/11) and pT0 was 54.5% (6/11). Radiologic response rate was 90.9% (PR10,CR0). Pts with either PD-L1+ or PD-L1- had pCRs. R0 resection rate was 100% (11/11). The average intraoperative blood loss was 172ml and the average hospitalization time after operation was 9 days (7-12days).No patient developed anastomotic leak and died due to treatment-related toxicity.

Conclusions

The addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) was well tolerated. The primary endpoint of pCR in at least 5/52 pts was surpassed with pCR in 5/11 pts post-surgery. The pCR was seen independent of PD-L1 score. The surprisingly good preliminary results have encouraged us to keep this phase II study ongoing.

Clinical trial identification

ChiCTR1900026240.

Legal entity responsible for the study

Shanghai Chest Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

128P - Clinical update with plasma and tumour-based genomic analyses in expansion part of phase I study of selective FGFR inhibitor E7090 (ID 391)

Presentation Number
128P
Lecture Time
09:00 - 09:00
Speakers
  • Chigusa Morizane (Chuo-ku, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The first-in-human phase I study of E7090 consists of dose-escalation (Part 1) and expansion (Part 2) cohorts, which has been conducted in Japan. The interim analysis results of Part 2, as of 31 July 2019, were reported (ASCO-GI 2020 #538). The interim analysis indicated that E7090 had a manageable safety profile and the promising clinical activity in cholangiocarcinoma subjects with FGFR2 rearrangements. In this study, we analyzed tumor tissue and plasma samples with NGS panels to assess baseline tumor gene characteristics and evolution of the ctDNA profile during E7090 treatment.

Methods

In part 2, subjects with cholangiocarcinoma harboring FGFR2 gene rearrangements (cholangiocarcinoma [CCA] cohort) and gastric cancer harboring FGFR2 gene amplification or FGFR2 protein high expression (GC cohort) were enrolled. Archival tumor tissue samples were analyzed with PGDx elio tissue complete NGS panel (PGDx; Personal Genome Diagnostics, Inc.). Plasma sample was collected at pre-treatment, every day 1 of odd cycle on-treatment and at discontinuation visit for ctDNA analysis with PGDx elio plasma resolve NGS panel.

Results

As of cutoff date, 3 June 2020, 6 subjects harboring FGFR2 rearrangements identified with break-apart fluorescence in situ hybridization were enrolled in the CCA cohort. Among six tumor tissue samples, one was failed in quality-check of NGS assay. Fusion gene partner in FGFR2 rearrangements was identified in 4 of the 5 tumor tissues as BICC1, CCDC6, POC1B, and SLMAP (n=1, each). FGFR2 rearrangements were also detected in baseline blood samples from 3 of the 6 subjects. In those three cases, the number of mutant reads for FGFR2 rearrangements in ctDNA assay decreased during treatment. ctDNA for FGFR2 (L617F, M537I) were detected in blood from 2 subjects at discontinuation visit. The updated efficacy and safety results in Part 2 will also be presented as of a new cutoff date.

Conclusions

The NGS assay illuminated FGFR2 fusion partners in archival tumor tissues. Besides, ctDNA analysis indicated ctDNA for FGFR2 rearrangements were decreased during E7090 treatments, and the potential clonal changes occurred as detections of ctDNA with FGFR2 mutations.

Clinical trial identification

NCT02275910.

Legal entity responsible for the study

Eisai.

Funding

Eisai.

Disclosure

C. Morizane: Honoraria (self): MSD K.K., Yakult Honsha, Novartis, Eisai, Teijin Pharma, Taiho Pharmaceutical; Research grant/Funding (institution): Yakult Honsha, Eisai, Taiho Pharmaceutical, Merck Biopharma, AstraZeneca, J-Pharma; Advisory/Consultancy: MSD K.K., AbbVie, Novartis, AstraZeneca,. M. Ueno: Honoraria (self): Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Ono Pharmaceutical, Merck Biopharma, MSD; Research grant/Funding (institution): Taiho Pharmaceutical, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Biopharma, Dainippon Sumitomo Pharma, Incyte, Yakult Honsha, Astellas. T. Ioka: Honoraria (self): Taiho Pharmaceutical, Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Otsuka; Advisory/Consultancy: Taiho Pharmaceutical, Otsuka, Shire, Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca, Dainippon Sumitomo Pharma, Baxalta/Shire, Eisai, Taiho Pharmaceutical, Taiho Pharmaceutical, Incyte, Takara Bio; Research grant/Funding (self): Taiho Pharmaceutical. M. Tajika: Speaker Bureau/Expert testimony: EA Pharma Co., Ltd., Olympus. M. Ikeda: Research grant/Funding (institution): Aslan Pharmaceuticals; Honoraria (self): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Sqiibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Micron; Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self), Advisory/Consultancy: Nihon Seriver; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis Pharma; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Mylan, Otsuka Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical, Teijin Pharma; Advisory/Consultancy: Takeda. K. Yamaguchi: Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (institution), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau/Expert testimony: Chugai Pharm; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Honoraria (institution), Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution): MSD oncology; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult Honsha. H. Hara: Advisory/Consultancy: Lilly, MSD, Ono: Honoraria (institution): Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Merck Biopharma, MSD, Ono, Sanofi, Taiho, Takeda and Yakult; Research grant/Funding (institution): Astellas, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Incyte, LSK BioPharma, Merck Biopharma, MSD, Ono, Pfizer, Taiho. A. Miyamoto: Research grant/Funding (institution): Eisai. S. Iwasa: Research grant/Funding (institution): Eisai, BMS, Daiichi-Sankyo, Ono, Bayer, Pfizer, Astellas; Honoraria (self): BMS, Ono, Chugai, Taiho. M. Muto: Research grant/Funding (institution): Eisai. T. Takashima: Honoraria (self): Taiho Pharmaceutical Co., Ltd; Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Daiichi-Sankyo K.K. K. Minashi: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd; Research grant/Funding (institution): Daiichi Sankyo Company, Limited. Y. Komatsu: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi-Sankyo, Yakult, Chugai, Taiho, Lilly, Sanofi, Ono, Nipro, Asahikasei, Nihonkayaku, Takeda; Research grant/Funding (institution): Eisai, MSD; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self): Kyowa Kirin, Merck Biopharma, Bristol-Myers Squibb, Shire Japan, Novartis Pharma, Pfizer, Mitsubishi Tanabe, Otsuka; Research grant/Funding (self): A2 Healthcare Corp., Astellas Pharma, Dainippon Sumitomo Pharma, NanoCarrier, Parexel International Corporation, IQVIA Inc., Syneos Health Clinical, Sysmex Corporation. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Merck biopharma; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Suibb; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo; Research grant/Funding (institution): Eisai; Honoraria (self): Nihonkayaku; Honoraria (self): Yaklut Honsya. T. Nakajima: Honoraria (self): Mochida Pharmaceutical, Celltrion Healthcare Japan, Merck Serono Co., Sawai Pharmaceutical Co., Bayer Yakuhin, Bristol-Myers Squibb, Teijin Pharma, Pfizer Japan Inc., Novartis Japan, Yakult Honsha Co., Nipro Co.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Sanofi K.K., Daiichi Sankyo Co., Eli Lilly Japan K.K., Nippon Kayaku Co., Ono Pharmaceutical Co., MSD K.K.; Research grant/Funding (institution): Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Eisai Co., Solasia Pharma K.K. T. Sahara: Full/Part-time employment: Eisai. S. Funasaka: Full/Part-time employment: Eisai. M. Yashiro: Research grant/Funding (self): Eisai Co., Ltd.; Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Research grant/Funding (self): Chiome Bioscience Inc.; Research grant/Funding (self): Five Prime Therapeutics, Inc. J. Furuse: Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin Pharma, Shionogi, EA Pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Fujifilm, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel p; Research grant/Funding (institution): Eisai, Fujifilm, Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan, Astellas Pharma, AstraZeneca, AbbVie, Shire, Merck Serono, Takara Bio, Chugai Pharma, Bayer Yakuhin, Otsuka, Novartis, MSD, Sumitomo Dainippon, J-Pharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

129P - Exploration of the best candidates for splenic hilar lymph node dissection (No.10 LND) based on long-term survival: Stage IIIA proximal gastric cancer may benefit from No.10 LND (ID 453)

Presentation Number
129P
Lecture Time
09:00 - 09:00
Speakers
  • Zu-Kai Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There is no conclusion regarding the indications for No.10 LND in advanced proximal gastric cancer (PGC). We aimed to explore the best candidates for splenic hilar lymph node dissection (No.10 LND) from the perspective of long-term survival.

Methods

Data of 995 patients who underwent laparoscopic radical gastrectomy from January 2008 to December 2014 were analyzed. Five hundred sixty-four patients underwent No.10 LND (No.10D+ group); the other 431 patients did not receive No.10 LND (No.10D- group). Propensity score matching was applied to reduce the effects of observed confounding. Study end points were overall survival (OS) and disease-free survival (DFS).

Results

No.10 LN metastasis was associated with pT or pN in multivariate logistic analysis (P<0.05). Recursive partitioning analysis obtained 3 groups of patients with different risks of No.10 LN metastasis: low-risk group (pT1-3N0-1), the No.10 LN metastasis rate was 0; intermediate-risk group (pT4aN0-1, pTanyN2, pT1-3N3a), the rate was 6.5%; and high-risk group (pT1-3N3b, pT4aN3), the rate was 30.5%. After matching, stepwise stratification survival analysis showed that for stage IIIA PGC, the No.10D+ group had significantly better survival than the No.10D- group (5-year OS: 68.9% vs. 48.1%%, P=0.001; 5-year DFS: 66.3% vs. 41.2%, P=0.001). Comparison of recurrence patterns in stage IIIA PGC showed that the No.10D+ group had a significantly lower overall recurrence rate (26.4% vs. 50.6%, P=0.004) and distant metastasis rate (11.1% vs. 38.1%, P<0.001) than the No.10D- group.

Conclusions

Stage IIIA PGC may achieve the benefit of long-term survival from No.10 LND. For PGC with stage IIIB and IIIC, although the No.10 LN metastasis rate is high, No.10 LND does not result in survival benefits, and neoadjuvant therapy before surgery is recommended.

Legal entity responsible for the study

The authors.

Funding

Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

130P - Reappraisal of the role of no. 10 lymphadenectomy for proximal gastric cancer in the era of minimal invasive surgery during total gastrectomy: A pooled analysis of 4 prospective trials (ID 466)

Presentation Number
130P
Lecture Time
09:00 - 09:00
Speakers
  • Qing Zhong (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it.

Methods

A total of 1068 patients (D2 group=409; D2+No. 10 group=659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed.

Results

No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2+No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size >5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2+No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations.

Conclusions

LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

131P - Prognostic value of tumour regression grading (TRG) in patients treated with neoadjuvant chemotherapy plus surgery for gastric cancer (ID 500)

Presentation Number
131P
Lecture Time
09:00 - 09:00
Speakers
  • Jian-Wei Xie (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The factors associated with a better tumor response rate and an optimal neoadjuvant chemotherapy regimen are uncertain. We aimed to validate the prognostic value of tumor regression grading (TRG) and explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery.

Methods

Three hundred forty-four AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting the tumor regression grading.

Results

For patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively(p=0.000). TRGs were independent risk factors for OS. Similar findings were observed in RFS. The oxaliplatin-based regimen was superior to the non-oxaliplatin-based regimen for the OS (38.4m vs 19.5m, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in non-signet ring cell carcinoma compared to the non-oxaliplatin-based regimen (53.7m vs 19.5m, respectively; p=0.011). However, Similar findings were not observed in RFS.

Conclusions

TRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with non-signet ring cell carcinoma.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

132P - Impact of increasing age on cancer- and noncancer-specific mortality in patients with gastric cancer treated by radical surgery: A competing risk analysis (ID 505)

Presentation Number
132P
Lecture Time
09:00 - 09:00
Speakers
  • Long-Long Cao (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To perform competing risk analysis and evaluate cancer- and noncancer-specific mortality in patients with gastric cancer after radical surgery.

Methods

A total of 5051 patients from our department (as training set) and a total of 7123 patients from the Surveillance, Epidemiology, and End Results (SEER) database (as validation set) were enrolled in the study. The cumulative incidence of cancer and noncancer-specific mortality was determined by univariate and multivariate competing risk analysis.

Results

The five-year cancer- and noncancer-specific cumulative incidence of death (CID) in the training set were 36.9% and 2.5%, respectively, which were significantly lower than that in the validation set (48.2% and 8.6%, respectively). Multivariable analysis showed that age, tumor site, tumor size and pTNM stage were independent predictors of gastric cancer-specific mortality and overall survival, whereas age was an independent predictor of gastric noncancer-specific mortality. Noncancer–specific CID surpassed cancer-specific CID for pTNM stage I patients after approximately 8 years of surgery, but never for stage II and III patients. Moreover, for stage I patients, the time point when noncancer–specific CID surpassed cancer-specific CID become earlier as age increasing, with only 3.5 years after surgery for patients more than 74 years of age.

Conclusions

Age is an independent predictor of gastric cancer- and noncancer specific mortality and overall survival for patients after radical surgery. For patients with stage I gastric cancer, noncancer-specific mortality is a significant competing event, with an increasing impact as age increases.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

133P - Which patient subgroup needs more attention in early treatment failure? A matched cohort study of treatment failure patterns in locally advanced gastric cancer (ID 692)

Presentation Number
133P
Lecture Time
09:00 - 09:00
Speakers
  • Dong Wu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The aim of this study was to compare the treatment failure patterns after laparoscopic (LG) and open gastrectomy (OG) in locally advanced gastric cancer (LAGC).

Methods

A total of 1792 LAGC patients who underwent radical resection between January 2010 and December 2016 were divided into an LG group (n=1557) and OG group (n=235). Propensity score matching was performed to balance the two groups. Dynamic hazard rates of failure were calculated using the hazard function.

Results

A total of 1175 LAGC patients were included after matching (LG group, n=940; OG, n=235). The treatment failure rate of the whole group was 43.23% (508/1175), accounting for 41.38% (389/940) and 50.64% (119/235) in the LG and OG groups, respectively. The static treatment failure pattern showed that only distant recurrence rate of the LG group was significantly lower than that of the OG group (22.02% vs. 28.94%, P=0.025). Landmark analysis showed a lower early treatment failure rate of the LG group in stage Ib-IIIb subgroup (P=0.004). Furthermore, dynamic hazard curve peaked at 9.4 months (Peak rate=0.0186) and then gradually declined. For stage Ⅰb to Ⅲb patients, time of peak failure hazard was 5.2 months earlier in the OG group (OG versus LG: 11.0 versus 16.2 months). Finally, LG was an independent protective factor associated with early treatment failure in stage Ib-IIIb patients (hazard ratio, 0.63; 95% CI, 0.43-0.93; P=0.019).

Conclusions

Given the differences in treatment failure patterns between LG and OG, shorter-interval surveillance for the first 2 years should be considered for stage Ib-IIIb patients after OG.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

134P - Effect of preoperative tumour under-staging on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (ID 700)

Presentation Number
134P
Lecture Time
09:00 - 09:00
Speakers
  • Mi Lin (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study aimed to evaluate the effect of preoperative tumour staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC).

Methods

Clinicopathological data of 2 346 patients who underwent RGGC were retrospectively analysed. The preoperative tumour-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients.

Results

There were 1 031 uTNM (44.0%) and 1 315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). Analysis of surgical and pathological factors showed that among patients with pT2, pT3+4, and pN+, all patients in group nTNM underwent D2 lymph node dissection (LND), whereas 15.1%, 1.3%, and 5.5% patients in group uTNM underwent D1 + LND, respectively. Among patients with pN0, the lymph node noncompliance rate was higher in the uTNM than in the nTNM group. Logistic analyses revealed that high BMI, tumour size <2 cm, early gross typing, and differentiated tumours in the upper stomach independently affected uTNM (P < 0.05).

Conclusions

Underestimated tumour staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

135P - Significance of lymphatic invasion in the indication for additional gastrectomy after endoscopic treatment (ID 169)

Presentation Number
135P
Lecture Time
09:00 - 09:00
Speakers
  • Hirohito Fujikawa (Yokohama, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In latest Japanese guidelines for gastric cancer treatment, the curability of endoscopic resection of patients with lymphovascular invasion (LVI) is classified as C-2 regardless of the presence or absence of other risk factors, and the standard therapy for C-2 is additional radical resection. On the other hand, pathological diagnosis after additional resection is often diagnosed as pN0, resulting in over treatment. The aim of this study was to investigate the clinical significance of LVI in the indication of endoscopic resection for gastric cancer, and also to evaluate the recently proposed stratification using the eCura system, a new scoring system for post-ESD curability of early gastric cancer.

Methods

A total of 164 patients who underwent additional surgical resection after endoscopic resection were enrolled in this study. The correlation between LVI and pathological lymph node metastasis was investigated and compared with the eCura system score.

Results

Patients with LVI positive (LVI (+)) were 64, and 100 were LVI negative (LVI (-)). Only 12 (7.3%) had lymph node metastasis, 8 (12.5%) in the LVI (+) and 4 (4.0%) in the LVI (-) (p = 0.04). In 9 cases, additional resection was indicated only by LVI, and none of the lymph node metastases was observed. The risk assessment using eCura system for all cases were low / intermediate / high risk: 103 (62.8%) / 42 (25.6%) / 19 (11.6%). The positive rate of lymph node metastasis was 4 (3.9%) / 4 (9.5%) / 4 (21.1%) respectively. Of the 9 cases resected by LVI alone, there were no cases classified as high risk.

Conclusions

Indications for additional surgical resection based on LVI alone are likely to be over treatment, and in such cases, careful judgment is required with reference to evaluation by the eCura system.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

136P - Modified ypTNM staging classification for gastric cancer after neoadjuvant therapy: A multi-institutional study (ID 705)

Presentation Number
136P
Lecture Time
09:00 - 09:00
Speakers
  • Wen-Wu Qiu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the AJCC Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging.

Methods

Clinicopathological data of 1791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the SEER database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th ypTNM staging and the modified staging for patients after neoadjuvant therapy.

Results

In the development cohort, the 5-year OS for AJCC stage I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stage IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < 0.001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < 0.001), predictive accuracy (mean difference in BIC: 64.94; NRI: 35.54%; IDI: 0.032, all p<0.001), and model stability (time-dependent ROC curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p<0.05).

Conclusions

We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th ypTNM staging, allowing more accurate assessment of the prognosis of GC patients after neoadjuvant therapy.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

137P - Clinical utility of circulating tumour DNA (ctDNA) in resectable gastric cancer (GC) (ID 974)

Presentation Number
137P
Lecture Time
09:00 - 09:00
Speakers
  • Mikhail Fedyanin (Moscow, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Circulating tumor DNA (CtDNA) has shown its negative prognostic value in a number of studies, however, data on the role of ctDNA in resectable gastric cancer (GC) are lacking. The aim of our study was to determine the prognostic value of ctDNA at various stages of the disease using our simple and cheap test.

Methods

This prospective study included patients with diagnosis of GC who received treatment from 2017 to 2019. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored by ddPCR in plasma samples taken before and after surgery in case of resectable GC (n=42) and before and during chemotherapy in case of advanced GC (n=13). The median time between surgery and blood sampling was 7 days (5-15 days, σ 2.3). The plasma sample was considered "positive” if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma.

Results

Tumor-derived mutations were found in plasma with sensitivity of 74.5% (n=55): in stage IV (n=13) – 92.3%, stage III (n=24) – 70.8%, stage II (n=11) – 81.8% and in stage I (n=7) – 100%. In the group with resectable GC 24 (57.1%) pts received adjuvant or perioperative chemotherapy. Detection of ctDNA before surgery did not affect DFS (HR 0.7, 95%CI 0.04-11.5, p=0.8). In 10 (23.8%) cases ctDNA was determined after surgery. Progression of the disease was detected in 6/10 (50%) pts with ctDNA(+) and 6/32 (18.8%) - in ctDNA(-) pts (p = 0.012). One-year DFS in ctDNA(+) and ctDNA(-) pts with resectable GC after surgery were 25.4% and 73.2%, respectively. ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 6.6, 95%CI 1.5-30, p =0.014).

Conclusions

A robust and economical assay of ctDNA detection is sensitive and demonstrates the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the GC. Further clinical validation of this approach is required in trails with modifications of the perioperative treatment, in terms of escalation and de-escalation, according to the content of ctDNA.

Legal entity responsible for the study

The authors.

Funding

This research is conducted under the auspices of the experimental governmental assignment of the Ministry of Health of the Russian Federation and coordinated by the FSBI “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Ministry of Health of the Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

138P - Prognostic importance of dynamic changes in systemic inflammatory markers for patients with gastric cancer (ID 428)

Presentation Number
138P
Lecture Time
09:00 - 09:00
Speakers
  • Ying-Qi Huang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Systemic inflammatory markers (SIM) are closely related to the prognosis of various tumors. However, most of the studies were mainly limited to examining the preoperative level of these markers to evaluate prognosis. Reports on the significance of postoperative SIM in predicting the long-term prognosis of gastric cancer (GC) were rare. Therefore, this study aims to explore the preoperative and postoperative longitudinal changes of SIM in patients with GC and the impact on long-term prognosis.

Methods

The prospectively collected data from 2180 patients with GC who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were retrospectively analyzed. Changes in SIM between preoperatively and 1-6 months and 12 months postoperatively were reported. Cox univariate and multivariate analyses were performed to determine the prognosis of GC.

Results

In multivariate analysis, higher preoperative systemic inflammation score (pre-SIS) was independent predictor of poor prognosis (P <0.05). Further analysis showed that the area under the curve (AUC) of pre-SIS for prediction of 5-year overall survival (OS) was highest [0.605 (95% CI 0.584-0.6250)]. The optimal time of remeasurement was 12 months postoperatively, based on a longitudinal profile of SIS and accuracy in predicting 5-year OS [AUC: 0.712 (95% CI 0.630 - 0.785)]. According to the association between the conversion of SIS and OS, we classified patients into three risk groups. Kaplan-Meier (K-M) curves showed significant differences in OS among risk groups. Further Cox multivariate regression analysis showed that only risk groups of SIS and pTNM stage were independent prognostic factors for OS.

Conclusions

The efficacy of SIS in predicting prognosis 12 months after surgery is superior, and the elevation of SIS 12 months after surgery predicts poor prognosis. These findings provide support for the remeasurement of SIS 12 months after surgery.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

139P - An intraoperative model for predicting survival and deciding therapeutic schedules: A comprehensive analysis of peritoneal metastasis in patients with advanced gastric cancer (ID 474)

Presentation Number
139P
Lecture Time
09:00 - 09:00
Speakers
  • Zhi-Yu Liu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

No specialized prognosis model for gastric cancer patients with peritoneal metastasis (GCPM) exists for intraoperative clinical decision-making. This study aims to establish a new prognostic model to provide individual treatment decisions for GCPM.

Methods

This retrospective analysis included 324 GCPM diagnosed pathologically by laparoscopy from January 2007 to January 2018 who were randomly assigned to different sets (227 in the training set and 97 in the validation set). A nomogram was established from preoperative and intraoperative variables determined by the Cox model. The peritoneal metastasis nomogram (PMN), was compared with the 15th peritoneal metastasis staging system (P1abc) for its predictive ability and clinical applicability.

Results

The median survival time was 8 (range, 1-90) months. In the training set, each PMN substage had significantly different survival curves (P<0.001), and the PMN was superior to P1abc based on the results of time-dependent receiver operating characteristic curve, C-index, Akaike information criterion and likelihood ratio chi-square analyses. In the validation set, the PMN was also better than P1abc in terms of its predictive ability. Of the PMN1 patients, those undergoing palliative resection (PR) had better OS than those undergoing exploratory surgery (ES) (P<0.05). Among the patients undergoing ES, those who received chemotherapy exhibited better OS than those who did not (P<0.05). Among the patients with PR, only PMN1 patients exhibited better OS following chemotherapy (P<0.05).

Conclusions

We developed and validated a simple, specific peritoneal metastasis model for GCPM that can predict prognosis well and guide treatment decisions.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

140P - Preoperative and postoperative C-reactive protein levels predict recurrence and chemotherapy benefit in gastric cancer (ID 693)

Presentation Number
140P
Lecture Time
09:00 - 09:00
Speakers
  • Li-Li Shen (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Preoperative and postoperative C-reactive protein (CRP) levels are related to the prognosis for cancer patients. This study aimed to explore the predictive value of combining the two in gastric cancer (GC) patients.

Methods

Patients in a clinical trial (NCT02327481) from January 2015 to April 2016 were analyzed. Receiver operating characteristic curves (ROCs) were generated. By calculating the areas under the curve (AUC) and the C-index, the discriminative ability of CRP during different periods were compared, including preoperative (pre-CRP), postoperative days 1, 3, and 5 (post-CRPs) and postoperative maximum CRP (post-CRPmax).

Results

Ultimately, 401 patients were included in this study. The median follow-up time was 42 months (range 3-51 months). For postoperative recurrence, the AUC and C-index of pre-CRP were 0.692 and 0.678, respectively, higher than those for post-CRPs, all p<0.05. Among post-CRPs, post-CRPmax had the highest AUC (0.591) and C-index (0.585). The optimal cut-off values for pre-CRP and post-CRPmax were 3.1mg/L and 77.1mg/L, respectively. Multivariate analysis showed both pre-CRP≥3.1mg/L (high-pre-CRP) and post-CRPmax≥77.1mg/L (high-post-CRPmax) were independent factors for recurrence-free survival (RFS). The model consisting of the pre-CRP, post-CRPmax and TNM had higher predictive ability and clinical utility. Adjuvant chemotherapy (ACT) benefit analysis for stage II/III GC showed patients with pre-CRP<3.1mg/L did not benefit from chemotherapy (RFS:90.0% nonchemotherapy group vs 80.7% chemotherapy group, p=0.557). In the high-pre-CRP group, only patients with high-post-CRPmax but not post-CRPmax<77.1mg/L benefited from chemotherapy (RFS:33.2% nonchemotherapy group vs 49.9% chemotherapy group, p=0.037). Similar findings were observed for overall survival.

Conclusions

Both pre-CRP and post-CRPmax, inexpensively and easily obtained, are independent predictors of recurrence for GC. ACT significantly prolonged the RFS for stage II/III GC with high-pre-CRP and high-post-CRPmax after R0 resection.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

141P - Low expression of CDK5RAP3 and UFM1 indicates poor prognosis in patients with gastric cancer (ID 706)

Presentation Number
141P
Lecture Time
09:00 - 09:00
Speakers
  • Ning-Zi Lian (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the correlation between different expression of CDK5RAP3 and UFM1 and the long-term survival of patients undergoing radical gastrectomy.

Methods

The expression of CDK5RAP3 and UFM1 in cancer and adjacent tissues of gastric cancer patients were detected, and their relationship with clinical pathological parameters and long-term prognosis were analyzed.

Results

Low expression of CDK5RAP3 was detected in 102 patients (78.5%), and UFM1 expression was low in 99 patients (76.2%), and the expression of the two was significantly positively correlated. Based on the co-expression of CDK5RAP3 and UFM1, we found that the low expression of CDK5RAP3 and UFM1 was closely related to the depth of invasion (P = 0.041), lymph node metastasis (p = 0.006), and TNM stage (P = 0.000). In Kaplan-Meier analysis, the prognosis of patients with low expression of CDK5RAP3 and UFM1 was significantly poorer than that of patients with high expression of CDK5RAP3 or UFM1 (p = 0.005), and could be used as an independent risk factor for the prognosis of the entire group of patients. The co-expression of CDK5RAP3 and UFM1 had the largest area under the ROC curve, and the patients’ long-term prognosis was better than the TNM stage alone, and has statistical significance (p <0.05).

Conclusions

The expressions of CDK5RAP3 and UFM1 are significantly reduced in gastric cancer tissues. The co-expression of CDK5RAP3 and UFM1 is an independent prognostic factor for gastric cancer. Combining the expression of the two can provide a more accurate prognostic model for predicting the overall survival of gastric cancer.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

142P - Prognostic analysis of patients with intra-abdominal infectious complications after laparoscopy and open radical gastrectomy for gastric cancer: A propensity score-matching analysis (ID 703)

Presentation Number
142P
Lecture Time
09:00 - 09:00
Speakers
  • Si-Jin Que (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the incidence and prognosis of intra-abdominal infectious complications (IaIC) after laparoscopic and open radical gastrectomy for gastric cancer.

Methods

The data of patients who underwent radical gastrectomy for gastric cancer at the Fujian Medical University Union Hospital from January 2000 to December 2014, retrospectively LAG and OG were used. 1:1 propensity score matching (PSM) was used to reduce biases. The incidence and prognosis of postoperative IaIC in the two groups were analyzed.

Results

The incidence of IaIC after OG and LAG was 4.1% and 5.1%, respectively(p=0.264). Cox multivariate analysis showed that IaIC was an independent risk factor for overall survival (OS) of patients undergoing gastrectomy (HR: 1.65, 95%CI: 1.23-2.20, p<0.001). Analysis also showed that LAG was an independent protective factor for OS with IaIC (HR 0.54, 95%CI: 0.31-0.96, p=0.036), and tumor diameter ≥ 50 mm (p=0.01) and pTNM III stage (p<0.001) were independent risk factors. After PSM, the five-year OS rate of patients with IaIC in the LAG was higher than that in the OG (51.1% vs. 32.4%, p=0.042). The independent preoperative risk factors for IaIC include male (OR 1.82, p=0.046) and BMI ≥ 25 (OR 1.88, p=0.021). Among patients with IaIC, the prognostic nutritional index (PNI) in OG group was similar to that in LAG group before operation (p=0.220), but lower than that in LAG group on the 1st, 3rd, and 5th day after surgery (p<0.05).

Conclusions

Compared to OG, LAG can improve the prognosis of patients with postoperative IaIC. For high-risk patients with IaIC, LAG is recommended.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

143P - Lymph nodes metastasis is the most important factor associated with pattern of recurrence following curative resection of gastric adenocarcinoma (ID 488)

Presentation Number
143P
Lecture Time
09:00 - 09:00
Speakers
  • Fu-Hai Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lymph node status is among the most important predictors of recurrence after curative gastrectomy. However, the impact of lymph node status on recurrence patterns remains unclear. We aimed to analyse recurrence patterns in completely resected gastric cancer (GC) with negative (pN0) or positive (pN+) lymph nodes.

Methods

We retrospectively assessed 1694 patients who underwent curative gastrectomy from January 2010 to August 2014. Patients were divided into pN0(n=655) and pN+(n=1039) cohorts. Timing and site(s) of recurrence were examined.

Results

Of all,517(30.5%) patients developed recurrent disease, and complete data on recurrence could be obtained in 493 patients.For the pN0 cohort, the patterns of recurrence were different according to pT stage: locoregional recurrence was the most common in patients with pT1-2 disease (57.1%), distant was the most common in patients with pT3 disease (57.1%), and peritoneal was the most common in patients with pT4a disease (66.7%). For the pN+ cohort, distant metastasis was the most common pattern irrespective of pT stage. The site-specific trend of recurrence showed that locoregional recurrence increased within 5 years in patients with pN0-2 disease but plateaued 3 years after surgery in patients with pN3 disease. Time to recurrence was significantly longer for the pN0 cohort compared with the pN+ cohort (median:25 vs 16 months=0.001). Moreover, post-recurrence survival was significantly better for the pN0 cohort than for the pN+ cohort (median:12 vs 6 months<0.001), especially in patients with non-peritoneal recurrence, late recurrence, single recurrence, and receipt of potential curative treatment.

Conclusions

There was a significant difference in recurrence patterns survival between node-negative and node-positive patients. For node-negative patients, follow-up strategies should be considered according to pathologic T stage, while the key to follow-up for node-positive patients is distant metastasis.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

144P - Clinical implication of DNA damage response gene in patients with stage II or III gastric cancer (ID 707)

Presentation Number
144P
Lecture Time
09:00 - 09:00
Speakers
  • In Gyu Hwang (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study was conducted to evaluate the relation of DNA damage repair (DDR) to clinical outcomes in gastric cancer patients with stage II or III treated gastrectomy.

Methods

From January 2005 to December 2017, 217 patients with stage II or III gastric cancer were analyzed for disease free survival (DFS) and overall survival according to DDR gene status. Immunohistochemical assessment of MLH1, MSH2, ARID1A, PARP-1, BRCA1 and ATM was performed in biologic samples.

Results

Among the 217 patients, the most commonly mutated DDR gene was MSH2 (n = 208, 95.9%), followed by BRCA1 (n = 191, 88.0%), MLH1 (n = 184, 84.8%), ARID1A (n = 170, 78.3%), ATM (n = 146, 67.3%) and PARP-1 (n=120, 55.3%). The high expression levels of PARP-1 group had a significantly longer 5-year OS rate as compared to low expression level of PARP-1 group (62.7% vs. 48.1%, HR 0.649, 95% CI 0.433-0.974, P = 0.035). In the multivariate OS analysis, TNM stage (HR = 5.202, P < 0.001), high expression PARP-1 (HR = 0.583, P = 0.011) and adjuvant chemotherapy (HR = 0.382, P <0.001) were only significantly prognostic factor.

Conclusions

A subgroup of patients with gastric cancer may benefit from targeted therapy. High PARP-1 expression may be a good prognostic factor for gastric cancer particularly, stage II or III gastric cancer post-surgery.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

145P - A nomogram for predicting the benefit of adjuvant chemotherapy after resection in patients with Borrmann type IV gastric cancer (ID 709)

Presentation Number
145P
Lecture Time
09:00 - 09:00
Speakers
  • Qing-Zhu Qiu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study sought to explore prognostic factors for patients with Borrmann type IV gastric cancer and to establish a predictive model for survival benefit of postoperative adjuvant chemotherapy in such patients.

Methods

This study reviewed the clinical data of patients who underwent curative surgery at Fujian Medical University Union Hospital from 2006 to 2014 for Borrmann type IV gastric cancer using a prospective database. Cox regression analyses were performed to identify prognostic factors that formed the basis for a nomogram and risk groups. Establishment of risk groups to identify patients with Borrmann type IV gastric cancer who would benefit from adjuvant chemotherapy.

Results

265 patients who underwent R0 resection were included in this study.Multivariate analysis showed that BMI, tumour differentiation, pT stage, pN stage, and ASA score were independent prognostic factors. Patients in the ACT-group had longer OS than patients in the SA-group, although the p-value for this difference was marginally above the threshold for statistical significance (23.8% vs. 10.9%, p=0.057). Stratified analysis showed that there was no significant difference in OS between the ACT-group and the SA-group for each AJCC stage (stage II: 40.6% vs. 29.8%, p=0.44; stage III: 21.4% vs. 9.7%, p=0.056).A nomogram was established based on these independent risk factors, and nomogram scores were used to divide all patients into a high-risk group (score>16), an intermediate-risk group (8<score≤16) and a low-risk group (score≤8).Further stratified analysis based on AJCC stage showed that the 3-year survival rate was higher in the adjuvant chemotherapy group than in the surgery alone group for low- and intermediate-risk patients in each AJCC stage, while high-risk patients in stage III did not significantly differ.

Conclusions

The nomogram that we established may effectively be used to identify patients with Borrmann type IV gastric cancer who would benefit from postoperative adjuvant chemotherapy. Postoperative adjuvant chemotherapy can improve survival in low- and intermediate-risk patients.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

146P - Red cell distribution width and mean corpuscular volume ratio as a promising new marker for chemotherapy effects in remnant gastric cancer: An analysis of a multi-institutional database (ID 738)

Presentation Number
146P
Lecture Time
09:00 - 09:00
Speakers
  • Kai-Xiang Xu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To study the value of the ratio of the red blood cell distribution width (RDW) to the mean corpuscular volume (MCV) (RMR) in predicting the efficacy of adjuvant chemotherapy (AC) in residual gastric cancer (RGC).

Methods

A total of 379 patients who underwent resection for RGC at 7 hospitals in China from January 2004 to January 2016 were analyzed. A nomogram predicts survival was established to evaluate the effect of RMR through a decision curve.

Results

According to the RMR cut-off point (0.177), all patients were divided into Group L (RMR<0.177) (n = 179) and Group H (RMR ≥ 0.177) (n = 160). Patients with stage II and III disease with a high RMR who received AC had a significantly better 3-year OS than those who did not receive AC (P = 0.048 and 0.044), while AC had no significant effect on the survival of patients with low RMR. The independent prognostic factors for OS in patients with RGC who underwent AC were used to establish a nomogram. The C-index was 0.795, and the decision threshold was 0-85%. According to the nomogram, patients were divided into low-benefit patients with AC (point < 102 points) and high-benefit patients with AC (point ≥ 102 points).

Conclusions

The predictive model based on RMR in this study can provide a simple and accurate indication for postoperative AC in patients with RGC. It is recommended that postoperative AC be administered to high-benefit patients with a score of ≥102 on the nomogram.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

148P - MCV-the ideal answer to predict the prognosis of remnant gastric cancer: An analysis from a multi-institutional database (ID 746)

Presentation Number
148P
Lecture Time
09:00 - 09:00
Speakers
  • Kai Weng (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the mean hemoglobin volume (MCV) in predicting the prognosis of residual gastric cancer (RGC).

Methods

A total of 225 RGC patients who underwent R0 resection in three hospitals in China from January 2003 to June 2015 were enrolled. The 3-year survival time were compared. Two-step regression was performed to analyze the effect of MCV on prognosis in RGC patients.

Results

A total of 208 patients were included in the final analysis, including 135 in Group L (MCV < 100 fl) and 73 in Group N (100 ≤ MCV < 120 fl). In different hospitals, there were different RGC occurrence times and initial gastric surgery intervals and different initial surgical reconstruction methods, the MCV value was not significantly correlated with hemoglobin content (R2=0.397). Comparing the 3 years overall survival time (OS) and disease-free survival time (DFS) with Group L, Group N patients were all better (P < 0.001). The stratified analysis showed that for stage III, with no anemia or mild anemia and chemotherapy, Group N patients had significantly better OS and DFS than the Group L patients (P < 0.05). Two-step multivariate analysis showed that MCV was an independent factor for the OS and DFS, and both the OS and DFS decreased as the MCV decreased (P<0.001).

Conclusions

MCV showed significant heterogeneity in patients with different RGC. Patients with low MCV have a significantly poor prognosis, and the MCV can therefore be a simple and effective indicator for assessing the prognosis of patients with RGC.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

149P - Molecular and clinical characteristics of patients with resectable gastric cancer (ID 796)

Presentation Number
149P
Lecture Time
09:00 - 09:00
Speakers
  • Zhi Zheng (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is one of the most common malignancies and a leading cause of cancer deaths worldwide. Currently, the genomic researches mainly focused on metastatic GC, but the clinico-molecular characteristics of resectable GC were poorly investigated.

Methods

A total of 47 resectable GC patients were enrolled. All kinds of genomic mutations were identified by next-generation sequencing (NGS) with Acornmed panel. Programmed death-ligand 1 (PD-L1) expression was analyzed by immunohistochemistry staining.

Results

Overall, a total of 582 mutations were identified from all the patients. TP53, LRP1B, ARID1A, and MDC1 were the most commonly mutated genes in resectable GC. Genomic data revealed significant mutual exclusivity between alterations in TP53 and PIK3CA (p < 0.05) and between those in TP53 and DICER1 (p < 0.05), as well as mutual co-occurence between alterations in FAT1 and ERBB3 (p < 0.05) and between those in FAT1 and NOTCH2 (p < 0.05). Additionally, ARID1A and APC alterations were significantly associated with poor differentiation (p < 0.05), and frequency of ARID1A mutations was markedly higher in intestinal-type GC than diffuse GC (p < 0.05). PD-L1 expression was analyzed in 45 tumors, and 33.3% of them showed positive PD-L1 expression. Further analysis demonstrated that KMT2D and ARID1A alterations were strikingly correlated with positive PD-L1 expression (p < 0.05). The median tumor mutational burden (TMB) in resectable GC was 6.38 mutations/Mb, and AR, CDH1, NOTCH2, and FAT1 mutations were remarkably associated with high TMB (p < 0.05). We further found that patients with positive PD-L1 expression tended to have low TMB (p = 0.057).

Conclusions

This study is of great significance in understanding the population characteristics of patients with resectable GC, which will be useful to guide personalized therapy and promote the clinical management in this population.

Legal entity responsible for the study

Zhi Zheng.

Funding

Beijing Municipal Science & Technology Commission.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

150P - Real-world assessment of the treatment patterns associated with unresectable advanced and metastatic gastric cancer in China (ID 778)

Presentation Number
150P
Lecture Time
09:00 - 09:00
Speakers
  • Xiao Sun (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) [including gastroesophageal junction cancer (GEJC)] has the second highest incidence and third highest mortality rate of all malignancies in China. For patients diagnosed with unresectable advanced or metastatic (UAM) GC, the prognosis and survival outcomes are extremely poor.

Methods

This was a retrospective real-world observational study using an oncology database operated by Digital China Health (DCH), which is comprehensive electronic health record (EHR) repository of patient demographics, clinical (including imaging, pathology.), medication use, healthcare resource use (HCRU) and cost data. Patients having ≥2 inpatient records with a primary ICD-10 code of GC were selected from Jan 1st, 2012 through Dec 31st, 2018. The first date of inpatient admission was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified as resectable vs. unresectable advanced or metastatic (UAM). Demographics, clinical parameters, medication utilization, HCRU, and costs incurred were tracked for these cohorts.

Results

A total of 7,464 patients met the inclusion/exclusion criteria, of whom 14.1% (n=1056) had UAM GC. The mean age at index date of patients with UAM GC was 57.7 (SD=11.3) years, with the vast majority male (70.5%). 69.3% (n=732) of patients with UAM GC received first line (1L) chemotherapy, the most frequent being S-1 + oxaliplatin (SOX, 22.7%) fluorouracil + oxaliplatin (FOLFOX, 12.6%) and capecitabine + oxaliplatin (XELOX, 11.2%). The average duration of 1L chemotherapy was 133.8 ± 115.9 days. Of these 1L line patients, 29.5% (n=216) went on to 2L treatment and 25.9 % (n=56) of 2L patients received 3L treatment. The main disease complications due to UAM GC were gastro-intestinal obstructions (7.8%) and ascites (7.5%). The main adverse drug events due to treatment were anemia (45.6%) and liver impairment (41.1%).

Conclusions

The majority of patients with UAM GC received 1L treatment. The top three regimens were SOX, FOLFOX and XELOX which seems consistent with Chinese Society of Clinical Oncology (CSCO) GC treatment guidelines.

Legal entity responsible for the study

Bristol-Myers Squibb Pharmaceutical Corp.

Funding

Bristol-Myers Squibb Pharmaceutical Corp.

Disclosure

X. Sun, Y. Qu: Research grant/Funding (self): Bristol-Myers Squibb. P. Navaratnam, H.S. Friedman: Research grant/Funding (self): Bristol-Myers Squibb. J. Gricar, H. Xiao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb.

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e-Poster Display Session (ID 87) Poster Display

151P - Treatment patterns, healthcare resource use, economic and survival outcomes associated with unresectable advanced metastatic gastric cancers in Taiwan (ID 902)

Presentation Number
151P
Lecture Time
09:00 - 09:00
Speakers
  • Chee Jen Chang (Taoyuan City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths in Taiwan. Even with significant strides that have been made in GC early detection and management in Taiwan in recent years, patients with GC (including gastro-esophageal junction cancer, GEJC) that present with unresectable advanced metastatic disease (UAM) remain at risk for poor survival outcomes.

Methods

This was a retrospective ‘real world’ observational study using the linked Taiwan National Health Insurance Research Database, which contains health claims data on almost the entire Taiwan population, and the Taiwan National Cancer Registry. Patients having at least one hospital record with a primary ICD-9 or ICD-10 code of GC/GEJC were selected from Jan 1st, 2013 through Dec 31st, 2018. The first date of GC/GEJC diagnosis was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified by staging, clinical presentation [i.e. resectable vs. unresectable advanced metastatic (UAM)]. Key characteristics such as demographics, clinical parameters, medication utilization, health care resource utilization, costs incurred, and survival were tracked for the overall population and both cohorts.

Results

A total of 3736 UAM GC patients were identified with a mean age of 68.0 (sd=15.2) years, with most patients being male (n=2248, 60.2%). The majority of UAM GC patients were Stage 4 (n=2270, 60.8%) and most patients were identified as having adenocarcinoma (n=2847, 76.2%). Nearly half the patients received 1st line (1L) therapy (n=1846, 49.4%) with the most common 1L therapies being Capecitabine + Oxaliplatin (n=604, 32.7% of 1L), S-1 (n=280, 15.2% of 1L) and Capecitabine monotherapy (n=209, 11.3% of 1L). Only 38.2% (n=1428) of patients survived 1 year with the annualized post-index GC-related costs being New Taiwan (NT) $ 396,590 (sd = NT$ 412,523).

Conclusions

The most common 1L chemotherapeutic treatments for UAM GC patients were Capecitabine + Oxaliplatin, S-1 and Capecitabine. In Taiwan, UAM GC patients appear to have poor survival and incur high GC-related costs, which suggests the need for new treatment options.

Legal entity responsible for the study

Bristol-Myers Squibb Pharmaceuticals Corp.

Funding

Bristol-Myers Squibb Pharmaceuticals Corp.

Disclosure

C.J. Chang, Y. Tsai, H.S. Friedman, P. Navaratnam: Research grant/Funding (self): Bristol-Myers Squibb. J. Gricar, H. Xiao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb.

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e-Poster Display Session (ID 87) Poster Display

153P - Mutational landscape of gastric cancer (GC) in adolescents and young adults (AYA) in Asia from 2015-2019 (ID 929)

Presentation Number
153P
Lecture Time
09:00 - 09:00
Speakers
  • Evelyn Yi Ting Wong (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is an aggressive cancer and it is thought that they have a worse prognosis in AYA due to delayed diagnosis and a more aggressive tumour biology. There is an increasing trend to adopt next-generation sequence (NGS) to identify tumour genomic alterations for precision medicine in AYA. We aim to study the differences in the mutational landscape of GC in AYA and how it correlates to outcomes in a single-centre high-volume Asian institution.

Methods

Patients diagnosed between 16-39 years old with GC between 2015 to 2019 in our centre, National Cancer Centre Singapore, were included in this study.

Results

A total of 50 AYA GC patients were referred to NCCS between 1st January 2015 and 31st December 2019. 7 patients were excluded from this analysis (3 due to incomplete data and 4 were neuroendocrine tumours). The median age (n=43) was 35(22-39) with 22 males (51.2%) and majority (53.5%, n=23) having signet ring cell carcinoma. 28 patients (65.1%) had metastatic disease at diagnosis. Out of the 43 patients, only 60.5%(n=26) and 58.1%(n=25) were tested for programmed death-ligand 1(PD-L1) and DNA mismatch repair (MMR) respectively. 1 patient (3.8%) had MLH 1 loss and 1 patient (4.5%) had PD-L1 percentage of more than 50% by using combined positive score (CPS). 32 patients (74.4%) had the human epidermal growth factor receptor 2(HER2) tested, of which 5 were HER2 positive (15.6%). With a median follow-up of 11 months, median OS was 16.0 months (range 0.5- 111.3 months). There was no significant differences between subgroups with regards to age(p=0.931), presence of signet-ring histology (p=0.135), histology grade (p=0.384) and HER2 positivity (p=0.66).

Conclusions

Gastric cancer in the young behaves differently and generally seem more aggressive in the young regardless of gender. Further studies to evaluate how the differences in the mutational landscape of gastric cancer in the adolescents and young adults impact prognosis and treatment paradigm.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

154P - A multicenter, prospective study of apatinib plus chemotherapy as neoadjuvant treatment for locally advanced gastric cancer (ID 486)

Presentation Number
154P
Lecture Time
09:00 - 09:00
Speakers
  • Yi-Hui Tang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Apatinib, a novel treatment option for chemotherapy-refractory advanced gastric cancer (AGC), has not yet been evaluated in patients with locally AGC. This trial investigated the efficacy and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally AGC.

Methods

Patients with M0 and either T2-T4 or N+ disease received apatinib (500 mg orally once daily on days 1-21 and discontinued in the last cycle) plus SOX (S-1, 40-60 mg orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1) given every 3 weeks for 2-5 cycles. D2 gastrectomy was performed 2-4 weeks after the last cycle. To further compare the efficacy and safety between apatinib plus SOX (ASOX group) and SOX alone (SOX group), we reviewed historical control patients receiving SOX as neoadjuvant chemotherapy at the central center. The primary end point was the R0 resection rate.

Results

Between July 2017 and June 2019, 48 and 58 patients were enrolled in the ASOX and SOX groups, respectively. Forty patients in the ASOX group (83.3%) and 47 patients in the SOX group (81.0%) underwent surgery, with R0 resection rates of 75.0% and 67.2%, respectively (P=0.382). The proportion of patients with T downstaging in the ASOX group was significantly higher than that in the SOX group (36.4% vs 18.5%, P=0.036). For patients with target lesions, the radiological response rate was significantly higher in the ASOX group (75.0% vs 38.5%, P=0.015). Moreover, the ASOX group was associated with significantly higher proportions of patients achieving major pathological response (25.0% vs 10.3%, P=0.046). Grade 3 toxicities occurred in 33.3% of the ASOX patients, and no grade 4 toxicities or drug-related deaths were observed.

Conclusions

Apatinib combined with SOX showed promising efficacy with an acceptable safety profile as the first-line neoadjuvant treatment for locally AGC.

Clinical trial identification

NCT03192735.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

155P - Surgical outcomes and technical performance of robotic versus laparoscopic total gastrectomy for gastric cancer: A prospective comparative study FUGES-014 (ID 720)

Presentation Number
155P
Lecture Time
09:00 - 09:00
Speakers
  • Hua-Gen Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Despite the increasing application of robotic surgery in patients with gastric cancer, however, for the complex minimally invasive total gastrectomy, no reports are supporting robotic surgery that can improve surgical performance and clinical outcomes.

Methods

In this prospective study, 50 patients were assigned to underwent robotic total gastrectomy (RTG) between March 2018 to February 2020 at a tertiary referral teaching hospital. Patients who underwent laparoscopic total gastrectomy (LTG) in the FUGES-002 study were matched to compare the surgical outcome and surgery task load of RTG and LTG. Objective structured assessment of technical skill (OSATS) was used to evaluate the technical performance.

Results

After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The total operative time in the RTG group was longer than that in LTG Group (217.1 minutes vs. 186.1 minutes, P < 0.001). Compared with LTG, the RTG group had less intraoperative blood loss (66.4 ml vs. 38.7 ml, P = 0.042). The average number of errors in the RTG group was 43.2 times/case, which was less than 53.8 times/case in the LTG Group (P < 0.001). Compared with LTG, RTG had a higher OSATS score (30.2 vs. 28.4, P < 0.001). RTG is superior to LTG in terms of respect for tissue, time and motion, instrument handling, and knowledge of specific procedures. The mean number of lymph nodes (LNs) retrieved in the RTG group and LTG group was 47.9 and 44.0, respectively. Significantly more extraperigastric LNs were retrieved in the RTG group than in the LTG group (20.2 vs. 17.5, P = 0.039). RTG group had a lower Surg-TLX score than LTG Group (33.2 vs. 39.8, P < 0.001). The postoperative recovery processes in the RTG group were shorter than those in the LTG Group. No significant difference was found between the RG and LG groups in the incidence (14.6% vs 16.7%, P = .86) or severity of complications.

Conclusions

In the complex radical gastrectomy, compared with traditional laparoscopic surgery, the use of the robotic system provides a technically superior operative environment and lower surgeon workload for minimally invasive surgery.

Clinical trial identification

NCT03524287.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

156P - Safety and feasibility of laparoscopic spleen-preserving splenic hilar lymphadenectomy during total gastrectomy for advanced proximal gastric cancer: A randomized clinical trial (ID 477)

Presentation Number
156P
Lecture Time
09:00 - 09:00
Speakers
  • Jian-Xian Lin (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The splenic hilar lymph node (No. 10 LN) dissection is still controversial for patients with advanced proximal gastric cancer (APGC) not invading the greater curvature. We aim to evaluate the short-term outcomes of laparoscopic spleen-preserving No. 10 lymphadenectomy (LSPL) for APGC not invading the greater curvature and the characteristic of No. 10 LN metastasis.

Methods

Between January 2015 and December 2018, 536 APGC patients with clinical stage cT2-4a/N0-3/M0 not invading the greater curvature were enrolled and randomized to receive laparoscopy-assisted total gastrectomy with either D2 lymphadenectomy (D2 group) or D2 lymphadenectomy without No. 10 LN dissection (D2- group). The morbidity and mortality within 30 days after surgery, and number of retrieved LNs between the two groups were compared. Risk factors and the metastasis rate of No.10 LN were analyzed.

Results

The present analysis included 263 patients in each group. There were no significant differences in the intraoperative and postoperative morbidity between the D2 and D2- groups (all P>0.05), and no mortality in both groups. There were more retrieved LNs in the D2 group than in the D2- group (45.1 vs 40.6, P=0.001). The metastasis rate of the No. 10 LN was 13.3% (35/263): 4.9% (2/41) in the early stage, and 14.9% (18/223) in the advanced stage. Pathological T (pT) stage and pN stage were related to No. 10 LN metastasis. The metastasis rates of No. 10 LN in T3-4a tumors located in the lesser curvature, posterior wall or multiple parts were all higher than 10%.

Conclusions

Experienced surgeons can safely perform LSPL for APGC with more retrieved LNs. For APGC located in the lesser curvature, posterior wall, or multiple parts with a clinical stage cT3-4a, the dissection of No.10 LN is recommended, but long-term follow-up is still required.

Clinical trial identification

NCT02333721.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

157P - Efficacy and safety of penpulimab (AK105), a new generation anti-programmed cell death-1 (PD-1) antibody, in upper gastrointestinal cancers (ID 687)

Presentation Number
157P
Lecture Time
09:00 - 09:00
Speakers
  • Amy Prawira (Sydney, Ontario, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Upper gastrointestinal (UGI) cancers are a group of highly aggressive malignancies with poor prognoses. Immunotherapy is emerging as an effective treatment option for some of these cancers. Penpulimab, a new generation anti-PD-1 monoclonal antibody, was engineered to optimize receptor occupancy by improving duration of drug binding, and to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function. Here, we present the preliminary antitumor and safety data on Penpulimab in patients (pts) with advanced UGI malignancies.

Methods

Pts with advanced cancers, relapsed or refractory to standard therapy but naïve to immune checkpoint inhibitors (ICIs), were enrolled in two phase I trials of Penpulimab (NCT03352531 and NCT04172506). Pts received Penpulimab IV at 1-10 mg/kg Q2W or 200mg Q2W until disease progression or unacceptable toxicity. Antitumor activity was investigator-assessed per RECIST v1.1 criteria.

Results

As of 1st July 2020, 67 pts with UGI cancers received Penpulimab for a median of 6 (1–64) doses. The antitumor activity of Penpulimab in the 60 pts evaluable for efficacy is shown below. 11/13 (85%) responders had ongoing responses at data cutoff date.

Pancreatic cancer (PCA), n=9 Cholangiocarcinoma (CCA), n=9 Gastric/ gastroesophageal junction (GEJ) cancer, n=19 Hepatocellular carcinoma, (HCC), n=23
ORR, % (95% CI) 11.1 [0.3, 48.2] 22.2 [2.8, 60.0] 26.3 [9.1, 51.2] 21.7 [7.5, 43.7]
DCR, % (95% CI) 33.3 [7.5, 70.1] 44.4 [13.7, 78.8] 42.1 [20.3, 66.5] 52.2 [30.6, 73.2]
Median DoR, months (range) 22.1+ 21.1 [0.03+, 21.1] NR [3.7+, 14.8+] NR [3.7+, 23.0+]
.

Treatment-related adverse events (TRAEs) occurred in 44.8% of pts. There were no discontinuations due to drug-related AEs or drug-related deaths. Grade ≥3 TRAEs occurred in 5 pts (7.5%) – raised liver enzymes (n=2), adrenal insufficiency (n=1) and hyponatraemia (n=1) in the same pt, intestinal obstruction (n=1), and hypertension (n=1).

Conclusions

Penpulimab was well tolerated and demonstrated encouraging antitumor activity with durable response in pts with advanced UGI cancers, including PCA and CCA, which are generally resistant to single agent ICI. Penpulimab in combination with anlotinib, a multi-targeted receptor tyrosine kinase inhibitor, is being evaluated in phase III studies for 1L HCC (NCT04344158) and 2L Gastric/GEJ (NCT04385550).

Clinical trial identification

NCT03352531; NCT04172506.

Legal entity responsible for the study

Akeso Biopharma Inc.

Funding

Akeso Biopharma Inc.

Disclosure

A.R.A. Mislang: Honoraria (self): BMS. A. Cooper: Honoraria (self): MSD; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Roche. X. Jin, K.Y. Kwek: Shareholder/Stockholder/Stock options, Full/Part-time employment: Akeso Biopharma. B. Li, M. Wang, D. Xia: Y. Xia: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Akeso Biopharma. A. Prawira: Research grant/Funding (institution), Non-remunerated activity/ies: Akeso Biopharma; Research grant/Funding (institution), Non-remunerated activity/ies: Beigene; Research grant/Funding (institution), Non-remunerated activity/ies: Corvus; Research grant/Funding (institution), Non-remunerated activity/ies: CStone; Research grant/Funding (institution), Non-remunerated activity/ies: Macrogenics; Research grant/Funding (institution), Non-remunerated activity/ies: Five Prime; Research grant/Funding (institution), Non-remunerated activity/ies: Virogin; Research grant/Funding (institution), Non-remunerated activity/ies: QBiotics; Research grant/Funding (institution): Arcusbio; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): ENB Therapeutics; Research grant/Funding (institution): Henlius; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): INXMed; Research grant/Funding (institution): Merck/MSD; Research grant/Funding (institution): Janssen. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

158P - A phase II study of trastuzumab with S-1 plus oxaliplatin for HER2-positive advanced gastric cancer (HIGHSOX study): Final report (ID 275)

Presentation Number
158P
Lecture Time
09:00 - 09:00
Speakers
  • Atsuo Takashima (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

We previously reported that trastuzumab (Tmab) combined with S-1 plus oxaliplatin (SOX) exhibited promising activity with well-tolerated toxicities in patients (pts) with human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) (Gastric Cancer 2019). Here, we report the results of a follow-up extension, including exploratory analyses performed to investigate predictive factors for treatment effects.

Methods

We conducted an open-label, phase II trial in pts with chemo-naïve, HER2-positive AGC. Pts received S-1 (40 mg/m2) BID orally on days 1–14, oxaliplatin (130 mg/m2) intravenously on day 1, and Tmab (course 1, 8 mg/kg; course 2, 6 mg/kg) intravenously on day 1 of a 21-day cycle. The primary endpoint was objective response rate (ORR); secondary end points included overall survival (OS), progression-free survival (PFS), and adverse events. A sample of 75 provided the study with 90% power to test a hypothesis of threshold RR of 50% and an expected RR of 65% at a one-sided significance level of 0.05 using the binomial test.

Results

Seventy-five patients were enrolled from June 2015 to January 2018. Pts characteristics were previously reported. In the full analysis set of 75 pts with a median follow up of 20.6 months, ORR was 70.7% (95% confidence interval (CI): 59.0–80.6) and the disease control rate was 93.3% (95% CI: 85.1–97.8). OS and PFS (median) were 20.6 (95% CI: 15.9–29.2) and 8.8 (95% CI: 7.3–11.8) months, respectively. In the exploratory analyses, both OS and PFS were longer in pts with HER2 3+ (n=55) than in pts with 2+ (n=20) [OS, 25.9 vs.16.3 months; hazard ratio (HR), 0.59; 95% CI: 0.329–1.053; P=0.07; PFS, 9.8 vs. 7.0 months; HR, 0.72; 95% CI: 0.421–1.229; P=0.23]. Pts who underwent conversion surgery (n=8) exhibited dramatically prolonged survival [OS, not reached; 3-year survival rate, 85.7% (95% CI: 33.4–97.9), PFS, 34.5 months (95% CI: 6.9–not reached)].

Conclusions

Tmab in combination with SOX exhibited promising therapeutic effects in pts with HER2-positive AGC. Efficacy was enhanced in pts with HER2 3+ and in those who underwent conversion surgery.

Clinical trial identification

UMIN000017602.

Legal entity responsible for the study

The authors.

Funding

Japanese Foundation for Multidisciplinary Treatment of Cancer.

Disclosure

A. Takashima: Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self): Eli Lilly; Honoraria (self): Ono; Honoraria (self): Yakult; Honoraria (self): Chugai; Research grant/Funding (self): Sumitomo Dainippon; Research grant/Funding (institution): LSK BioPartners. K. Minashi: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Ono. S. Kadowaki: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Ono; Research grant/Funding (institution): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Bayer; Honoraria (self): Merck. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Daiichi Sankyo; Honoraria (self): Dainippon Sumitomo; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD. K. Amagai: Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution): MSD; Honoraria (self): Eli Lilly; Honoraria (self): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Daiichi Sankyo; Honoraria (self): Hisamitsu. N. Machida: Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self): Eli Lilly ; Honoraria (self): Ono; Honoraria (self): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Nippon Kayaku; Honoraria (self): Daiichi Sankyo; Honoraria (self): MSD. M. Goto: Honoraria (self): Taiho; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Ono; Honoraria (self): Takeda; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Novartis; Honoraria (self): Bayer; Honoraria (self): Mochida. N. Ishizuka: Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self): MSD. D. Takahari: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self): Eli Lilly; Honoraria (self): BMS. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

159P - Open surgery can improve the 3-year postoperative survival in some patients with advanced gastric cancer compared with laparoscopic surgery: A multicenter, propensity score matching, in-depth analysis (ID 702)

Presentation Number
159P
Lecture Time
09:00 - 09:00
Speakers
  • Ze-Ning Huang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The impact of time on the efficacy of advanced distal gastric cancer (ADGC) remains unclear. At 3 years postoperatively, the efficacy of oncologic surgery for ADGC needs to be confirmed.

Methods

A total of 1256 patients with ADGC at two teaching institutions in China from April 2007 to December 2014 were enrolled. The general data of the two groups were matched using propensity scores. Restricted mean survival time (RMST) was used to compare survival.

Results

After matching, 461 patients each in the open distal gastrectomy (ODG) and laparoscopic distal gastrectomy (LDG) groups were analyzed. The 3- and 5-year overall survival (OS) and disease-free survival in ODG group were comparable to those in LDG group. RMST-stratified analysis showed that the 3-year RMST of ODG group was similar to that of LDG group (-1.38 years, P=0.163) in cT4a patients, whereas the 5-year RMST had significant differences between groups (-8.36 years, P=0.005). In further stratified analysis, when patients with cT4a and tumor was >5 cm, the 3-year RMST of ODG group was similar to that of LDG group (0.98 year, P=0.480); however, the 5-year RMST was significantly longer in ODG group (4.67 years, P=0.042). Multivariate regression analysis showed that ODG is a protective factor for 5-year OS in patients with cT4a and tumors >5 cm.

Conclusions

Beyond 3 years, ODG can improve the survival of patients with serous infiltration and tumors >5 cm by reducing the risk of recurrence. The present findings can serve as a reference for the preoperative selection of GC surgery options and the setting of follow-up time for clinical studies.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

160P - Phase II study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma (ID 879)

Presentation Number
160P
Lecture Time
09:00 - 09:00
Speakers
  • Ning Li (Zhengzhou, China)
Location
On-Demand e-Poster Display, Virtual Me