Browsing Over 852 Presentations
510P - Characteristics and outcome of small cell lung cancer patients (SCLC) transformed from adenocarcinoma after tyrosine kinase inhibitors treatment
- Bo Zhang
- Bo Zhang
- Jianlin Xu
- Shuyuan Wang
- Yanwei Zhang
- Jie Qian
- Rong Qiao
- Jun Lu
- Lele Zhang
- Yiming Zhao
- Baohui Han
Abstract
Background
Small cell lung cancer (SCLC) transformation was a rare mechanism associated with EGFR-TKI resistance. However, knowledge in this field is very limited due to the low prevalence. The aim of the study was to investigate characteristics and outcome of SCLC transformed from adenocarcinoma after TKI treatment.
Methods
From January 2013 to December 2017, SCLC patients enrolled into our standardized large database were screened and we also performed a literature review of published articles. Clinical characteristics and prognosis were retrospectively analyzed after combining our data with reported cases.
Results
A total of 87 eligible patients were included in this study. Median TKIs exposure time and SCLC transformation time were 15.0 months (95% CI, 13.3 months to 16.7 months) and 20.5 months (95% CI, 17.9 months to 23.1 months), respectively. Female gender (OR, 2.10, 95% CI: 1.18-3.73, P = 0.01) and mutation in exon 19 deletion (19del, OR, 1.95, 95% CI: 1.05-3.60, P = 0.03) were independent positive predictors for SCLC transformation. 94.0% (63/67) of patients still retained the initial mutations (19del or 21L858R) after SCLC transformation, however, the median PFS was only 2.0 months (95% CI, 1.2 months to 2.8 months, n = 13) when treated with TKI monotherapy. 38 patients were treated with etoposide combined with cisplatin or carboplatin (EC/EP) (7 combined with TKIs and 2 combined with radiotherapy), conferring a median PFS of 6.0 months (95% CI, 4.8 months to 7.2 months) after SCLC transformation.
Conclusions
Efficacy of EC/EP may not be that bad when treating SCLC transformed from lung adenocarcinoma. EGFR-TKIs confer limited efficacy after SCLC transformation even with the presence of sensitive mutations, thus they should not be recommended routinely.
Legal entity responsible for the study
Professor Baohui Han.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
126P - STING, an immune biomarker for colorectal cancer
- Hongjae Chon
- Hongjae Chon
- Dae J. Kim
- Chan Kim
Abstract
Background
STING is an innate immune sensor for cytosolic DNA. The activation of STING signaling is indispensable in Type I interferon response and the evocation of anti-cancer immune response by CD8+ T cells. The aim of this study is to characterize intratumoral STING expression pattern and its clinical implication in colorectal cancer (CRC).
Methods
We analyzed STING and CD8 expression in 225 CRC patients who underwent surgical resection. Clinicopathological variables and survival outcomes were analyzed according to STING expression level.
Results
Distinct STING expression was observed in tumor specimens of CRCs. Patients with higher STING expression seemed to have early stage cancer (P = 0.001) with increased intratumoral CD8+ T cell infiltration (P < 0.001), and less frequent lymphovascular invasion (P = 0.02). Compared to CRC patients with lower STING expression, those with higher STING expression had longer overall survival (P < 0.001) and recurrence-free survival (P < 0.001). The Cox proportional hazard model adjusted for age, stage, and CD8+ T cells, revealed that higher STING expression is an independent prognostic factor for a better overall survival (P = 0.012, hazard ratio 0.573, 95% CI 0.370 – 0.886).
Conclusions
We have confirmed the distinct STING expression in CRC and demonstrated its independent prognostic value for the survival outcome, thereby suggesting the intratumoral STING expression as a potential immune biomarker for CRC.
Legal entity responsible for the study
Hongjae Chon.
Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the the Ministry of Science, ICT & Future Planning (grant NRF-2016R1D1A1B03934012 to H.C.).
Disclosure
All authors have declared no conflicts of interest.
Castration-resistant prostate cancer: Case presentation: Indications for SABR, treatment planning and delivery techniques
- Melvin Lee Kiang Chua
- Melvin Lee Kiang Chua
Immuno checkpoint blockade in patients with brain metastases
- Simon Ekman
- Simon Ekman
Discussion / Q&A
119P - Poor-prognosis Locally Advanced Rectal Cancer is Defined by a Molecularly Distinct Subtype
- Jing Zhang
- Jing Zhang
- Lijun Shen
- Yaqi Wang
- Yun Deng
- Lifeng Yang
- Juefeng Wan
- Zhen Zhang
Abstract
Background
TNM stage is still the only prognostic tool used in clinical practice to treat patients but it fails to accurately predict outcomes. Categorization of locally advanced rectal cancers into distinct subtypes using a combination of qPCR-based biomarkers could provide insight into variability in outcomes.
Methods
We used a PCR-based assay to detect 30 genes (LARCassigner-30) in 197 locally advanced rectal cancer samples, collected prospectively from patients treated with neoadjuvant chemoradiation and surgery from January 2007 to December 2012 in Fudan University Shanghai Cancer Center. 197 patients were randomly divided into training queuing of 98 cases and validation of the cohort of 99 cases. Median follow-up time is 58 months. Association with 5-year overall survival, disease-free survival, recurrent rate and metastatic rate was evaluated using Cox proportional hazards models.
Results
Baseline clinical characteristics and postoperative pathological features were similar between the training cohort and the validation cohort. The overall survival rate of LARCassigner-30 type 1 patients was lower than that of type 2 patients in the training and validation cohorts (p < 0.01), tumor-free survival rate decreased (p < 0.01); local recurrence rate increased (p < 0.01), distant metastasis rate increased (p < 0.01), the difference was statistically significant. In the training cohort, LARCassigner-30 type 1 patients with locally advanced rectal cancer were found to have poorer response to neoadjuvant chemoradiation than type 2 patients (p = 0.023), but they were not verified in the validation cohort.
Conclusions
We developed qPCR-based classifiers LARCassigner-30 that performs well at predicting the outcomes in locally advanced rectal cancer.
Legal entity responsible for the study
Institutional Review Board of Fudan University Shanghai Cancer Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
491O - Carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab in first-line metastatic squamous NSCLC: results from the KEYNOTE-407 East Asia subgroup
- Terufumi Kato
- Terufumi Kato
- SungSook Lee
- Ying Cheng
- Gyeong-Won Lee
- KiHyeong Lee
- Alexander Luft
- José Trigo
- Rina Hui
- Beatrix Balint
- Andrew Robinson
- Isamu Okamoto
- Gregory J. Gerstner
- Luis Paz-Ares
- Xiaodong Li
- Yue Shentu
- Bilal Piperdi
- Ali Tafreshi
Abstract
Background
Primary results from the global, randomized, double-blind, phase 3 KEYNOTE-407 study (NCT02775435) demonstrated superior OS, PFS, and ORR with pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel (chemo) in patients with previously untreated squamous NSCLC. Here we report results from the East Asia subgroup of KEYNOTE-407.
Methods
In KEYNOTE-407, patients with untreated metastatic squamous NSCLC were randomized 1:1 to carboplatin 6 mg/mL/min and paclitaxel 200 mg/m2 Q3W or nab-paclitaxel 100 mg/m2 weekly (investigator’s choice) plus pembrolizumab or saline placebo Q3W for 4 cycles followed by pembrolizumab or placebo Q3W for a total of 35 treatment cycles. Randomization was stratified by taxane (paclitaxel vs nab-paclitaxel), PD-L1 (tumor proportion score [TPS] <1% vs ≥ 1%), and region (East Asia vs other). Primary endpoints were OS and PFS (by blinded independent central review [BICR]); ORR by BICR was a secondary endpoint. For the East Asia subgroup, OS and PFS HRs were estimated using an unstratified Cox regression model; between-group difference in ORR was estimated using an unstratified Miettinen & Nurminen method.
Results
Of 559 patients randomized globally, 106 (19.0%) with largely similar baseline characteristics were enrolled from East Asia (pembrolizumab plus chemo, n = 54; placebo plus chemo, n = 52). After median follow-up of 6.7 (range, 0.5–18.9) mo among patients from East-Asia, median (95% CI) OS (16.6 [16.6–NR] mo vs 9.5 [7.5–NR] mo) and PFS (6.3 [5.3–10.2] mo vs 4.1 [3.5–5.2] mo) were longer in those who received pembrolizumab plus chemo vs placebo plus chemo, with HRs of 0.44 [95% CI, 0.22–0.89] and 0.49 [95% CI, 0.30–0.82], respectively. ORR was 63.0% vs 34.6%, respectively (ORR difference, 28.3% [95% CI, 9.3–45.4]). Grade ≥3 AEs occurred in 83.3% of patients in the pembrolizumab plus chemo arm vs 80.8% of those in the placebo plus chemo arm.
Conclusions
Consistent with overall results from KEYNOTE-407, pembrolizumab plus chemo extended OS and PFS, and almost doubled ORR vs placebo plus chemo in patients from East Asia with previously untreated metastatic squamous NSCLC. No new safety signals were observed.
Editorial acknowledgement
Sheri Arndt.
Clinical trial identification
MK-3475-407, NCT02775435.
Legal entity responsible for the study
Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
T. Kato: Grants, personal fees: Abbvie, Astellas, AZ, BI, BMS, Chugai, Eli Lilly, Kyowa Kirin, MSD (inc. for this study), Novartis, Ono, Parexel, Pfizer, Quintiles, Taiho, Roche, Merck Serono, Sumitomo Dainippon. K. Lee: Grants: MSD during the conduct of the study; Personal fees for advisory boards: BMS, MSD outside of the submitted work. R. Hui: Advisory board member: MSD, AstraZeneca, Roche, BMS, Novartis; Speaker honoraria: MSD, Novartis, AstraZeneca, Roche, BMS. B. Balint: No financial interests or arrangements with the sponsor that may bias the results of the study. A. Robinson: Grants: Bristol-Myers Squibb, Merck, Roche, AstraZeneca. I. Okamoto: Grant support: AstraZeneca during conduct of the study. Additional grant support, personal fees (honoraria): AstraZeneca, Ono, BMS, Chugai, Lilly, Taiho, Boehringer Ingelheim and Pfizer outside the submitted work. L. Paz-Ares: Grant and funding to institution for conduct of this study: MSD; Personal fees for advisory boards: MSD, BMS, AstraZeneca, Lilly, Pfizer, Merck-Serono, Roche, Amgen, Takeda, Incyte outside the submitted work. X. Li: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Y. Shentu, B. Piperdi: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. All other authors have declared no conflicts of interest.
137P - Prognostic value of staging FDG PET/CT in patients with metastatic colorectal cancer
- Eun Kyoung Choi
- Eun Kyoung Choi
- Jin Kyoung Oh
- Yong-An Chung
Abstract
Background
The aim of the study was to assess the prognostic value of staging PET/CT in patients with metastatic colorectal cancer (mCRC) with respect to the location, number, and maximum standardized uptake value (SUVmax) of metastatic lesions.
Methods
We retrospectively reviewed the staging F-18 FDG PET/CT images of 136 patients (mean age 63.5 y; range 31-88 y; 80 men, 56 women) with mCRC and their medical records. Using the PET/CT images, the location of metastasis, number of lesions per organ, and maximal SUVmax of metastatic lesions in each organ were identified on PET/CT images of the patients. The patients were grouped according to the location and number of metastatic lesions: group I, a single lesion confined within a single organ or location; group II, multiple lesions within a single organ or location; and group III, multiple metastases in multiple organs or locations. Correlations between the location, number, and SUVmax of metastatic lesions and overall survival (OS) were evaluated.
Results
Of 136 patients, hepatic metastasis was found in 104, pulmonary metastasis in 36, distant lymph node metastasis in 18, peritoneal metastasis in 15, and bone metastasis in 13. The SUVmax range for metastatic lesions was 4-9.9 (mean 7.8; median 7.5). According to the sub-classification, groups I, II, and III were consisted of 35, 58, and 43 patients, respectively. The patients without bone and distant lymph node metastasis, with metastatic lesion of SUVmax <7.5, from groups I and II had significantly longer OS compared with those of the patients with bone and distant lymph node metastasis, with metastatic lesion of SUVmax ≥ 7.5, and from group III. Moreover, multivariate analysis showed that bone metastasis and higher SUVmax of metastatic lesion (≥ 7.5) were independent prognostic factors for OS.
Conclusions
The presence of bone metastasis and high SUVmax of metastatic lesion in staging PET/CT might have prognostic value in predicting the survival of mCRC patients.
Legal entity responsible for the study
Jin Kyoung Oh.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
325P - Comparing different normal tissue complication probability (NTCP) models of radiation-induced temporal lobe injury after intensity-modulated radiation therapy for nasopharyngeal carcinoma
- Lei Zeng
- Lei Zeng
Abstract
Background
To compare different normal tissue complication probability (NTCP) models to predict the incidence of radiation-induced temporal lobe injury (TLI) for nasopharyngeal carcinoma (NPC) patients who received intensity-modulated radiotherapy (IMRT).
Methods
Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively. A large number of dose-volume effect models has been fitted to data on the occurrence of TLI after IMRT for NPC. The following models were considered: (1) Lyman model and (2) logit-formula with dose-volume histogram (DVH) reduced to generalized equivalent uniform dose (EUD), (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose model. The fitting was done with the maximum likelihood method.
Results
Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. As assessed qualitatively and quantitatively, the Lyman-EUD model fitted the data very well (a=∞, m = 0.07, TD50=81Gy), and was superior to the remaining models. So it demonstrates that temporal lobe is a serial organ. Temporal lobe mean dose did not correlate to TLI.
Conclusions
Our study clearly confirms a dose effect for TLI after IMRT for NPC. The Lyman model was the most accurate predictor for the incidence of TLI. It suggests that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe.
Legal entity responsible for the study
Jiangxi Cancer Hospital.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Targeting BRCA mutations and BRCAness in patients with metastatic breast cancer: Evidences from clinical trials
- Young-Hyuck Im
- Young-Hyuck Im
YO37 - The usefulness of radiotherapy for intubated patients with squamous cell carcinoma of the lung.
- Shinya Hiraoka
- Shinya Hiraoka
- Kengo Ogura
- Yasuhiro Kosaka
- Toshiyuki Imagumbai
- Takayuki Hattori
- Takashi Ogata
- Masaki Kokubo
Abstract
Case Summary
Background: Intubated patients due to tracheal stenosis by the tumor rarely received radiotherapy because most of radiation oncologists think radiotherapy for these patients very risky. Therefore, the effect of radiotherapy for these patients is poorly identified. The objective of this study is to investigate the effective of radiotherapy for intubated patients due to tracheal stenosis by the tumor.
Methods: A total of 3 patients with tracheal intubation due to tracheal stenosis by squamous cell carcinoma of the lung undergoing radiotherapy in 2016 were identified.
Results: Three patients were admitted to the hospital because of tracheal stenosis due to locally advanced squamous cell carcinoma of the lung. Patient age was 67, 75, and 84 years old, respectively. Just a month before admission, their Eastern Cooperative Oncology Group Performance Status was 0. After admission, bronchoscopy with transbronchial biopsy was taken and they got intubated on the mechanical ventilator. The prescribed dose was 28 Gy at 7 Gy per fraction, 20 Gy at 4 Gy per fraction, and 25 Gy at 5 Gy per fraction. Two patients were extubated on Day 14 of admission. They were also able to return to their social activities one month after admission. They were given re-irradiation 4 months after completion of radiotherapy because of the loco-regional recurrence. One survived for 21 months without any treatment after re-irradiation. The other was alive 7 months after admission, but the follow-up was interrupted after that. Unfortunately, one patient was discontinued radiotherapy at 16 Gy because of her bad general medical condition. She died due to acute respiratory distress syndrome on day 22. No one was given chemotherapy. Acute toxicity related to radiotherapy was not experienced. Malfunction of the ventilator was concerned, but no ventilator broke down during radiotherapy.
Conclusion: Palliative radiotherapy enabled two of three patients to relief symptoms and return to their social activities. Our experiences suggest that intubated patients due to tracheal stenosis by squamous cell carcinoma of the lung can receive radiotherapy safely and can be rehabilitated well.
36P - Metabolic Syndrome in Luminal-Type Non-Metastatic Breast Cancer during Hormonal Treatment Does it really have impact on prognosis?
- Kartika W. Taroeno Hariadi
- Kartika W. Taroeno Hariadi
- Mardiah S. Hardianti
- Johan Kurnianda
- Yasjudan R. Putra
- Teguh Aryandono
Abstract
Background
Metabolic Syndrome (MetS) has been shown as risk and prognostic factors of cancer. MetS affects the prognosis of breast cancer patients differently according to the race, breast cancer type, metabolic component, cancer treatment and concomitant medication. Whether MetS influence the prognosis of the luminal type breast cancer patients has not been confirmed yet. This study aims at analyzing the association between metabolic syndrome and disease-free survival of luminal-type breast cancer patients.
Methods
Data from medical record of all non-metastatic breast cancer patients, luminal-type, HER-2 negative, receiving chemotherapy ± radiotherapy and or hormonal therapy, and diagnosed between 2013 – 2018 were extracted and included for this retrospective study. Cases with previous or concomitant malignancy, or which recurrent event is not assessed by imaging or cytology, or incomplete data, or follow up cannot be done were excluded from study. MetS is defined as Modified NCEP ATP III for Asian. Kaplan-Meir Survival analysis were used to estimate cumulative survival time for recurrence based on MetS status of breast cancer patients.
Results
There were 127 non-metastatic, luminal-type breast cancer included for analysis. Median age of subjects was 54-year-old (36-84 years). MetS were found in 47.2% of breast cancer patients with luminal type. Obesity and overweight occured in 40.9%; hypertension in 50.4%; low LDL in 51.2%; hyperglycemia in 56.7%; and increased waist circumference in 56.7%. Relapsed rate was similar between MetS and metabolic normal patients. Eighteen out of 60 luminal-type breast cancer patients with MetS were recurred (30%) as well as 33.3% of breast cancer without MetS. Median disease-free survival in MetS luminal type breast cancer was 84 months while in non MetS was 106 months (95% CI 16,6-151.3; p < 0.62).
Conclusions
In luminal-type breast cancer patients, MetS was not a prognostic factor for relapse. Concomitant medications used for metabolic syndromes, or cancer treatment may obscure the results.
Clinical trial identification
Ethics Committee Approval KE/FK/0670/EC/2018.
Legal entity responsible for the study
Medical And Health Research Ethics Commitee (MHREC) Faculty of Medicine Gadjah Mada University - Dr Sardjito Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.