Background

Rectal cancer is one of the most common causes of cancer-related deaths worldwide. Circulating tumor cells (CTCs) are rare aneusomic cells that detach from the primary solid tumors and enter the circulation, and can initiate metastasis. Detection of CTCs in liquid biopsies is a promising strategy for diagnosing, monitoring the relapse and metastasis, and evaluating cancer prognosis and therapy. However, CTC detection in patients with rectal cancer is limited in routine clinical practice. The aim of this study was to elucidate the role of CTCs in patients with rectal cancer.

Methods

A total of 142 patients with rectal cancer were enrolled. CTCs were measured in the peripheral blood (preoperatively, immediately postoperative, day 1 and 7 postoperatively) and inferior mesenteric vein (intraoperatively), usingthe CTCBIOPSY® System (YZYBIO Company, Wuhan, China). General information, initial diagnosis and the integrated pathological information of all participants were recorded. Data Analysis was performed using the Chi-square test, with 95% confidence intervals (95% CIs) as the threshold for statistical significance.

Results

CTCs were detected (≥1 CTC per 5ml blood) in the blood preoperatively more frequently in patients with a higher grade of TNM stage (c2=7.317, P = 0.048) and there was a trend of association (c2=6.457, P = 0.012). CTC detection in the blood was significantly associated with T stage (c2=12.912, P = 0.005) and N stage (c2=17.587, P < 0.001) preoperatively. It proved that age and gender were uncorrelated variables with CTC detection. Compared with CTC detection preoperatively, postoperative CTCs are firstly increased and then decreased.

Conclusions

CTC detection is closely related to TNM stage in patients with rectal cancer, and so it may be a way to predict clinicopathological stage by detecting CTCs. The postoperative CTCs are potential biomarkers for rectal cancer prognosis but needed to be verified in more studies.

Clinical trial identification

NCT02955173; Pre-results.

Legal entity responsible for the study

Qilu Hospital of Shandong University.

Funding

Ministry of Science and Technology of China.

Disclosure

The author has declared no conflicts of interest.

Background

Head and Neck Squamous Cell Carcinomas (HNSCC) account for 4.5% of global cancer incidences and mortality respectively. In India however, HNSCC accounts for 17% of cancer related incidences and 15% of cancer related mortality. Standard of Care (SoC) systemic treatment approaches for HNSCC are based on randomized clinical trials which do not sufficiently consider patient specific features of the tumor. We evaluated the efficacy of personalized treatment in a cohort (n = 31) of advanced refractory HNSCC, where patient-specific treatment regimens were based on Encyclopedic Tumor Analysis (ETA).

Methods

Freshly biopsied tumor tissue and peripheral blood of patients were used for integrational multi-analyte investigations as part of ETA, which included gene alterations and gene expression, as well as in vitro chemosensitivity and response profiling (CRR) of viable tumor cells. Patients received individualized therapy recommendations based on ETA. All patients underwent whole body PET-CT and brain MRI scans prior to start of treatment, and follow-up scans every 6-8 weeks. Treatment response was evaluated as per RECIST 1.1 criteria.

Results

Among the 31 patients who received personalized treatment guided by ETA, partial response (PR) was observed in 14 patients and Stable Disease (SD) in 16 patients yielding an Objective Response Rate (ORR) of 45.2% and Clinical Benefit Rate of (CBR) 96.8%, respectively. Patients were followed up for a median of 146 days (Range 42 – 368). At most recent follow-up 1 patient showed disease progression, whereas Progression Free Survival was observed in 30 patients. Median Progression-Free Survival was 146 days. No grade IV adverse events were observed. There were no treatment related deaths. Most common Grade III adverse events included Fatigue, Anorexia, Thrombocytopenia, Neutropenia and Oral Mucositis. Most patients reported qualitative improvements in symptomatic and functional status.

Conclusions

ETA guided treatments can offer viable treatment options in advanced refractory HNSCC yielding meaningful ORR and disease control in majority of patients.

Legal entity responsible for the study

The Authors.

Funding

Datar Cancer Genetics Limited.

Disclosure

R. Nagarkar: Advisory / Consultancy: Datar Cancer Genetics Limited. D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. V. Palwe: Non-remunerated activity/ies: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Ghaisas: Full / Part-time employment: Datar Cancer Genetics Limited. N. Srivastava: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Leadership role, Shareholder / Stockholder / Stock options, Licensing / Royalties: Datar Cancer Genetics Limited.

Background

Genomic rearrangements involving neurotrophic tropomyosin receptor kinase 1, 2, or 3 (NTRK1/2/3) result in constitutively active tropomyosin receptor kinase (TRK) fusion proteins that are oncogenic drivers in multiple pediatric and adult cancers. Larotrectinib is a selective TRK inhibitor approved by the US Food and Drug Administration in 2018 for the treatment of TRK fusion cancer based on a primary analysis in 55 patients from 3 clinical trials [Drilon et al. NEJM 2018]. Here, we report median duration of response (DOR) data in the primary cohort and updated data in an expanded cohort of 159 patients with TRK fusion cancer treated with larotrectinib, with 153 (55 primary + 98 supplemental) evaluable for efficacy.

Methods

Patients with TRK fusion cancer detected by local molecular profiling were treated with larotrectinib across 3 studies (NCT02122913, NCT02637687, NCT02576431). Disease status was assessed by investigators using RECIST 1.1. Data cut-off was February 19, 2019.

Results

In the primary cohort of 55 patients with a median follow-up of 26 months, the median DOR in 44 patients with complete or partial responses was 35.2 months (95% CI 21.2–not evaluable [NE]), with 17 progression events and 27 responses ongoing (range 1.6–44 months). Median progression-free survival in the primary cohort was 25.8 months (95% CI 9.9–NE), with 27 patients having progressed. In the expanded combined dataset, the most common tumor types included soft tissue sarcoma (n = 36), infantile fibrosarcoma (n = 29), thyroid carcinoma (n = 26), salivary gland carcinoma (n = 21), and lung cancer (n = 12). Median age was 43 years, ranging from < 1 month to 84 years; 33% < 18 years. The overall response rate was 79% (95% CI 72–85), with complete responses in 16%. Adverse events were mostly grade 1–2; 13% of patients had a grade 3–4 event related to larotrectinib. Only one patient discontinued due to an adverse event related to larotrectinib.

Conclusions

These data confirm the marked tissue-agnostic efficacy and long durability of response in patients with TRK fusion cancer treated with larotrectinib. Larotrectinib demonstrated a favorable long-term safety profile. Screening patients for NTRK gene fusions should be considered.

Clinical trial identification

NCT02122913, NCT02637687, NCT02576431.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

F. Doz: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (self): Celgene; Advisory / Consultancy: Bayer; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Servier. L. Mascarenhas: Speaker Bureau / Expert testimony: Bayer. J. Berlin: Research grant / Funding (institution): PsiOxus; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): AbbVie (pharamcyclics); Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): FivePrime; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Macrogenics; Honoraria (self): Nestle; Advisory / Consultancy: Rafeal; Advisory / Consultancy: Seattle Genetics; Honoraria (self): Eisai; Advisory / Consultancy: Taiho; Advisory / Consultancy: Armo. All other authors have declared no conflicts of interest.

Background

Interleukin-4 (IL-4) is an important modulator in the immune response of macrophages, B and T cells to stand in front of infections and malignancy. This study aimed to assess the association between IL-4 gene 590CT polymorphism and risk of hepatocellular carcinoma (HCC) on top of viral hepatitis.

Methods

This study was conducted on 220 patients and 60 apparently healthy individuals. One hundred and twenty patients with HCV infection (group 1) classified as sixty patients with liver cirrhosis and sixty with HCC, one hundred patients with HBV infection (group 2) classified as fifty with liver cirrhosis and fifty with HCC. Virus status of the patients was confirmed by measuring HBsAg, HCV antibodies and real time PCR. Liver cirrhosis was assessed by laboratory investigations, abdomino-pelvic ultrasound and CHILD score. Patients with HCC were diagnosed by triphasic CT, alphafeto-protein level (AFP) and biopsy. The studied groups were genotyped for IL-4 590C/T gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

IL-4 590C/T gene analysis detected significant variation between studied groups, regarding genotype and allele frequencies (p = 0.025 and p = 0.002 respectively). There were higher frequencies of CC genotype and C allele in HCC and cirrhotic hepatitis C patients than controls. C allele had higher prevalence in HCC than cirrhosis in HBV patients. CT+CC genotype carriers had an elevated HCC risk odd ratio (OR): 4.6 [95% CI: 1.5 –14] and OR 3.6 [95% CI: 1.1 –11.6], in HCV and HBV patients in contrast to controls. C allele was associated with increased cirrhotic and HCC risk in HCV infected patients with OR = 4 [95% CI: 1.8 – 8.8] and OR = 2.3 [95% CI: 1.1 – 5.2] versus control group. In HBV patients C allele showed higher HCC risk with OR = 4.2 [95% CI: 1.8 – 9.5] when compared to controls.

Conclusions

IL-4 590C/T gene polymorphism may have a role in occurrence of HCC on top of liver cirrhosis.

Legal entity responsible for the study

authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Elderly STS patients (pts) have different clinicopathological feature and health status compared to younger pts. The optimal management for mSTS remained unclear.

Methods

From January 2011 to December 2017, mSTS pts in National Taiwan University Hospital and ≥65-years-old at the time of metastatic disease diagnosis were included. The clinicopathological features and the chemotherapy (C/T) received were collected.

Results

61 mSTS pts ≥65 y/o were identified; the median age was 74 (range 65- 89); male: female 46%: 54%. The most common histologies were liposarcoma (23%), angiosarcoma (19.7%), and sarcoma NOS (18%). 50 (82%) pts received at least one-line of C/T and the median lines of C/T received was 1 (range 1-5). Anthracycline (exclusive of liposomal doxorubicin (lip-dox)) and ifosfamide were administered to 16 (32%) and 8 (16%) pts; 16 (32%) pts received combination chemotherapy as first-line systemic treatment (tx). Another 9 (18%) and 6 (12%) of patients received lip-dox and oral cyclophosphamide (o-cyclo), as first-line systemic tx. With a median follow-up time of 6.8 months (mos), the median OS was 9.57 mos (95% CI 6.03-22.87 mos); pts who received at least one line of C/T had a numerically but not statistically significant better OS as compared to those who did not receive any C/T (17.50 vs 6.83 mos, p = 0.25). The benefit of systemic C/T were similar for pts aged 65-74 vs ≥ 75 (p for interaction = 0.72). In terms of tx efficacy, the PFS and 1-year OS rate of first-line lip-dox, o-cyclo, and doxorubicin were 7.37 mos and 42%; 16.29 mos and 83%, and 6.97 mos and 40%, respectively. The histologies of mSTS pts who received o-cyclo and lip-dox tx are shown in the table. In multivariate Cox model, only liposarcoma histology had a trend for OS impact (HR 0.4, 95% CI 0.15-1.08, p = 0.07). Table:

410P Histology distribution of pts receiving lip-dox and o-cyclo as first-line therapy

Conclusions

Systemic C/T should be considered for elderly mSTS pts. Less toxic tx such as o-cyclo or lip-dox could be considered for selective histologies.

Legal entity responsible for the study

The authors.

Funding

Taiwan Maple Orthopedic Association.

Disclosure

All authors have declared no conflicts of interest.

Background

To compare the long-term oncologic outcome of laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for patients with stage Ia1-Ib3 cervical cancer.

Methods

A retrospective data of stage Ia1-Ib1 cervical cancer patients who underwent LRH and ARH at Sun Yat-sen University Cancer Center from Jan. 2012 to Dec. 2015 was collected. Patients were re-classified according to the 2018 FIGO staging system for cervical cancer and screened out 679 cases with stage Ia1-Ib3 cervical cancer. Propensity score matching (PSM) was performed by software SPSS 22.0, and a total of 268 patient pairs (LRH-ARH) were enrolled and analyzed. Oncologic outcomes and prognosis factors were compared between patients undergoing LRH vs. ARH.

Results

(1) Baseline characteristics after PSM: There were no statistical differences between LRH and ARH, but only in grade (p = 0.001). (2) Operation related data: The operative time [(228±90) vs (210±54) min], estimated blood loss (EBL) [(129.5±138.2) vs (207.8±204.6) ml], and the length of hospital stay [(10.6±3.5) vs (12.6±3.5) days] in the LRH group were significantly shorter compared with ARH group (all P < 0.001). (3) Recurrence and survival data: There was a significant difference in the 5-year disease-free survival (DFS; 86.4% vs 95.6%, p = 0.002) and 5-year overall survival (OS; 92.2% vs 97.5%, p = 0.017) between the LRH group and ARH groups. (4) Prognosis factors: In univariate and multivariat analysis, the results showed that surgical approach was common independent prognostic factor for OS and DFS. (5) Stratified analysis: Stratified analysis in low-risk patients with cervical cancer showed that, even in stage Ib1 patients with tumor size <2 cm, there were significant differences for OS and DFS between LRH and ARH group (all P < 0.05). Besides, ALR group only showed better DFS than LRH group in patients with no lymph vascular space invasion.

Conclusions

Our results suggest that, for patients with stage Ia1-Ib3 cervical cancer, ARH results in more benefits for OS and DFS compared with LRH. Even in low-risk patients, ARH is still an oncologically safer alternative.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

National Natural Science Fund.

Disclosure

All authors have declared no conflicts of interest.

Background

Helicobacter pylori-induced aberrant JAK/STAT3 signaling contributed to the development of gastric cancer. We hypothesize that activated STAT3 may epigenetically repress it’s targets by DNA methylation. The object of this study is to identified the diagnostic and prognostic value of novel STAT3 targets that are hypermethylated in gastric cancer.

Methods

Fifty patients’ clinical data and genomic DNA were collected from the Changhua Christian Hospital, Taiwan. DNA methylation microarray was used to analyze the methylation status in AGS gastric cancer cells and patient samples with different STAT3 status. Bioinformatic analyses was carried out to identify STAT3 targets with differential methylation status. Bisulphite pyrosequencing was designed and performed in cancer and normal tissue to examine the methylation level of the target genes. Receiver operating character (ROC) curve and the survival analysis were examined.

Results

We found that promoter hypomethylation of PCDHB15, a potential STAT3 target, was observed in AGS cells depleted with STAT3, while promoter hypermethylation was observed in patient samples with activated STAT3. Cell line studies found that treatment with the DNMT inhibitor, 5azaDC, restored PCDHB15 expression in AGS. Pyrosequencing in various cell lines, including AGS, MKN28, MKN45, SNU1 and SNU16, demonstrated hypermethylation of the PCDHB15 promoter. Compared to the cancer tissue, a lower PCDHB15 methylation was observed in matched adjacent tissue (P = 0.001) and gastritis tissue (P < 0.001). Interestingly, Kaplain-Meier analysis found that patients with higher PCDHB15 methylation had longer survival as compared to patients with lower methylation (p = 0.03).

Conclusions

Our study indicate that methylated PCDHB15 promoter may be associated with development of gastric cancer. Patients with higher PCDHB15 methylation are prone to have better prognosis.

Legal entity responsible for the study

The authors.

Funding

This study was supported by a grant from Taichung Veterans General Hospital (RVHYCY-107008).

Disclosure

All authors have declared no conflicts of interest.