bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of DNA repair gene based on stratification of gastric cancer.
Authors: Chang Jinjia , Xu Midie , Sun Hui , Li Wenhua , Ye Min , Weng Weiwei , Zhu Xiaodong 
Published: January 2019

12 Background: DNA repair genes can be used as prognostic biomarkers in many types of cancer. We aimed to identify prognostic DNA repair genes in patients with gastric cancer (GC) by systematically bioinformatic approaches using web-based database. Methods: Global gene expression profiles from altogether 1,325 GC patients’ samples from six independent datasets were included in the study. Clustering analysis was performed to screen potentially abnormal DNA repair genes related to the prognosis of GC, followed by unsupervised clustering analysis to identify molecular subtypes of GC. Characteristics and prognosis differences were analyzed among these molecular subtypes, and modular key genes in molecular subtypes were identified based on changes in expression correlation. Multivariate Cox proportional hazard analysis was used to find the independent prognostic gene. Kaplan-Meier method and log-rank test was used to estimate correlations of key DNA repair genes with GC patients’overall survival. Results: There were 57 key genes significantly associated to GC patients’ prognosis, and patients were stratified into three molecular clusters based on their expression profiles, in which patients in Cluster 3 showed the best survival (P < 0.05). After a three-phase training, test and validation process, the expression profile of 13 independent key DNA repair genes were identified can classify the prognostic risk of patients. Compared with patients with low-risk score, patients with high risk score in the training set had shorter overall survival (P < 0.0001). Furthermore, we verified equivalent findings by these key DNA repair genes in the test set (P < 0.0001) and the independent validation set (P = 0.0024). Conclusions: Our results suggest a great potential for the use of DNA repair gene profiling as a powerful marker in prognostication and inform treatment decisions for GC patients.
Gls-010, a novel anti-PD-1 mAb in Chinese advanced gastrointestinal tumor: Result of a phase Ib clinical trial.
Authors: Lin Shen , Gong Jifang , Xu Yingying , Zhang Xiaotian , Peng Zhi , Qi Changsong , Li Guochun , Meng Haijin , Liu Zhen , Wang Hui , Chen Chris , Li Jing , Zheng Yong , Lee Johnathan , Zhang Yan , Zhang Qiang , Jin Ge , Yang Yining , Zhao Guodong 
Published: January 2019

125 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Phase Ia exhibited good result of tolerance and 240mg fixed dose was selected. Phase Ib is to explore efficacy and biomarkers in different types of advanced cancer. Here we report the preliminary result in Chinese gastrointestinal (GI) tumor patients (pts) from the phase Ib. Methods: All pts enrolled received GLS-010 240mg every 2 weeks. Tumor response was assessed by RECIST 1.1 every 8 weeks. Adverse events (AEs) were graded by NCI CTCAE v4.03. Several biomarkers were evaluated, including PD-L1 by IHC, tissue tumor mutation burden (tTMB) by whole exome sequencing (WES) from FFPE tissue, blood TMB (bTMB) by the multi-gene panel based next-generation sequencing (NGS) from blood ctDNA. Results: Until September 2018, 23 pts (including 10 gastric cancer or GC, 10 esophagus cancer or EC, and 3 biliary tract cancer or BTC) were enrolled in the phase 1b. The median dosing number was 4 (range: 1~16). The most common treatment related AEs included haemoglobin decreased (16/23, G1-2), leukopenia (6/23, G1-2), fever (4/23, G1), blood bilirubin increased (4/23, G1-3), ALT increased (3/23, G1), etc. Treatment–related grade 3-5 AEs include 1 multiple organ dysfunction syndrome, 1 interstitial lung disease and 1 blood bilirubin increased. 21 pts received response evaluation. Four patients achieved partial response (PR), including 1 GC (1/9), 2 EC (2/10), and 1 BTC (1/2). 2 subjects had stable disease (SD) at Week 8, and were still in treatment. No apparent correlation was observed between treatment response and PD-L1 expression. However, both tTMB and bTMB data obtained from 18 patients support positive correlation to tumor response. The tTMB level of 3 PR pts with valid data is significantly higher than that of 9 PD pts (P = 0.036). The bTMB level of 4 PR pts with valid data is significantly higher than that of 10 PD pts (P = 0.049). Conclusions: GLS-010 showed promising efficacy and acceptable safety in Chinese patients. For Chinese GI tumor TMB may be a useful biomarker to predict the treatment response to PD-1 inhibitor. Comparing to tTMB, bTMB may be of more future value due to its applicability in clinical practice.
Hyperprogressive disease (HPD) during nivolumab (Nivo) or irinotecan (IRI) as salvage line in patients with metastatic gastric cancer (MGC).
Authors: Sugimoto Naotoshi , Otsuka Tomoyuki , Hasegawa Akiko , Yagi Toshinari , Kudo Toshihiro , Fujiishi Koto , Nishio Minako , Yamamoto Sachiko , Fujisawa Fumie , Imamura Fumio 
Published: January 2019

126 Background: Nivo was approved in heavily treated MGC patients in September 2017 in Japan. HPD have been reported in patients with various tumor types treated with anti-PD-1/PD-L1 antibody therapy, but no data was existed in gastric cancer. Methods: We retrospectively compared tumor growth kinetics (TGK) on Nivo or IRI as salvage line and TGK on last treatment in patients with MGC in our hospital. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. HPD was defined as a TGKR ≥ 2. Results: 51 patients have been treated Nivo (n = 31) or IRI (n = 20) as salvage line before Aug 2018 in our hospital. The median age was 67 years (range 37-81) in Nivo and 68 years (range 46-80) in IRI.; 20 males and 11 females in Nivo and 16 males and 4 females in IRI; PS 0-1/2 score 19/12 in Nivo and 19/1 in IRI. Thirty-five patients (Nivo : IRI = 16:19) had target lesions according to RECIST 1.1 and performed CT pre, baseline and during treatment. HPD were observed in seven patients (44%) with Nivo. On the contrary, only one patient (5%) experienced HPD with IRI. Median PFS and OS (HPD vs. non-HPD) were 2.1 versus 3.5 months (HR: 0.29 (0.083-0.98), p = 0.046) and 5.3 versus 6.6 months (HR: 0.44 (0.078-2.5), p = 0.35) with Nivo. The rate of grade3-4 irAEs were colitis (6%), interstitial pneumonia (6%), and mytosis (3%) with Nivo. No treatment-related death and pseudo-progression were observed. Conclusions: HPD is more common with Nivo compared with IRI in patients with MGC as salvage line and associated with poor PFS in patients treated with Nivo. Further analysis will be warranted.
M1a disease should be reconsidered in esophageal cancer staging system from the perspective of treatment response and survival after definitive concurrent chemoradiotherapy.
Authors: Chung Tae Ryong , Kim Jie-Hyun , Lee Ik Jae , Cho Yona , Jung Da Hyun , Park Jae Jun , Youn Young Hoon , Park Hyojin 
Published: January 2019

13 Background: M1a node involvement based on the 6th edition AJCC staging system was classified as regional node involvement in the 7th edition of esophageal squamous cell carcinoma (ESCC). However, the clinical significance of M1a node involvement based on the 6th edition staging system has not been well established. Thus, we analyzed the prognostic value of M1a node in patients of ESCC after definitive chemoradiotherapy (CCRT). Methods: A total of 188 ESCC patients had M0 disease based on the 7th edition AJCC classification, of which 31 (16.5%) of them were reclassified to the M1a patient group under the 6th edition AJCC classification. After definitive CCRT, we compared the basic characteristics of two groups, analyzed the rate of complete remission (CR), recurrence, finally assessed overall survival (OS), and disease-free survival (DFS) of each group. Results: Among 31 patients reclassified to M1a disease, 21 patients (67.7%) had subclavian nodes and 10 patients (32.3%) had celiac nodes. The median follow-up period was 18.3 months. The M1a group showed a significantly lower survival rate not only in median OS (M1a 16.4 months, M0 42.7 months, P = 0.015), but also in 5-year OS (M1a 10.8%, M0 41.2%). Three of 31 patients (9.7%) in the M1a group achieved CR, while 41 of 157 patients (26.1%) in the M0 group achieved CR ( P = 0.048). However, there was no recurrence in the M1a group after achieved CR during follow-up period. Conclusions: Among ESCC patients after completing definitive CCRT, M1a patients according to the 6th AJCC staging system showed lower CR rate and OS rate compared with M0 disease patients. M1a nodes should be differentiated from regional node involvement.
A multicenter study of trimodality therapy for patients 75 years and older with esophageal cancer.
Authors: McDonnell Niamh Anna , Lester Scott , Haddock Michael G. , Halfdanarson Thorvardur Ragnar , Mahipal Amit , Spears Grant M. , Liao Zhongxing X. , Blackmon Shanda H , Hallemeier Christopher Leigh , Lin Steven H. , Merrell Kenneth 
Published: January 2019

131 Background: Trimodality therapy is the standard of care for patients with resectable cancer of the esophagus. However, patients ≥75 years have been underrepresented or excluded from landmark clinical trials to date. We investigated the feasibility and safety of treatment of esophageal cancer with trimodality therapy in patients’ ≥ 75 years. Methods: We performed a retrospective review of all patients ≥75 years who received trimodality therapy for esophageal cancer in 3 high volume tertiary cancer institutions from June 2007 to June 2013. All patients received neoadjuvant radiation with concomitant chemotherapy followed by esophagectomy. Toxicities and clinical outcomes were abstracted from the electronic medical record and partially from a prospectively maintained database. Overall and disease-free survival were estimated using the Kaplan-Meier method. Results: Five hundred seventy patients were treated with trimodality therapy for esophageal cancer from 2007-2013. Of these, 38 patients (7%) were 75 or older at the time of diagnosis. At diagnosis, comorbidities included coronary artery disease (32%), atrial fibrillation (11%) and COPD (13%). The majority of patients (87%) received 50.4Gy/28 fractions. 5-fluorouracil (5-FU)/cisplatin was the most common chemotherapy regimen (37%), followed by 5-FU/docetaxel (24%). A total of 13 patients (34%) developed acute grade ≥3 toxicity associated with neoadjuvant therapy. The most common acute grade 3 toxicities were haematological (10%), nausea (8%), esophagitis (5%) and fatigue (5%). Significant postoperative complications included respiratory (empyema, ARDS, pleural effusion) (39%), arrhythmia (32%), anastomotic leak (5%), and ileus (5%). There were 2 deaths (5%) within 90 days of surgery: one was secondary to empyema, the other developed DIC and sepsis. Median overall survival and disease free survival were 4.4 and 2.3 years respectively. Conclusions: Trimodality treatment is a reasonable approach for management of carefully selected elderly patients with esophageal cancer, with similar rates of cancer outcomes, and treatment related morbidity and mortality as compared to younger patients.
Impact of double-flap technique for reconstruction after proximal gastrectomy.
Authors: Asanuma Kazuki , Kawakubo Hirofumi , Mayanagi Shuhei , Nakamura Rieko , Irino Tomoyuki , Fukuda Kazumasa , Wada Norihito , Kitagawa Yuko 
Published: January 2019

134 Background: Proximal gastrectomy (PG) has been performed for proximal early gastric cancer as a minimally invasive procedure. In PG, gastroesophageal reflux disease (GERD) becomes problem, thus several techniques have been reported to reduce GERD. So far, we have mainly performed the method of anastomosis based on double stapling technique (DST) using a trans-oral anvil delivery system for reconstruction after PG. For preventing GERD, we recently introduced double-flap technique (DFT) reported to be more physiological anti-reflux reconstruction which can prevent GERD. So, this study shows superiority of DFT compared to DST. Methods: Patients who have undergone PG for proximal gastric cancer during Jan. 2012 to Jul. 2017 in our hospital were reviewed as candidates. Operation time, blood loss, postoperative anastomotic complication, postoperative hospital stay, postoperative reflux symptom or endoscopic findings, intake of proton pump inhibitor (PPI) at 1 year after the operation, and postoperative nutritional status were retrospectively investigated. Results: DFT was performed in 26 patients whereas DST was performed in 38 patients. Average operation time and postoperative hospital stay was not significant in both groups (DFT group; 275.8±41.4 minutes, 13.6±8.9 days, DST group; 252.2±82.9 minutes, 15.2±7.2 days, respectively). As for postoperative complications higher than Clavien-Dindo Grade III, one case of suture failure was observed in DFT group. Postoperative reflux symptoms and endoscopic findings of gastroesophageal reflux were significantly frequent in DST group compared to DFT group (Reflux symptoms, DFT group : DST group = 0 : 7(p = 0.03), Endoscopic findings, DFT group : DST group = 1 : 11(p < 0.01) , respectively). There were significantly more cases of PPI taking one year after the operation in DST group(DFT group : DST group = 8 : 28 (p < 0.01) ). Average weight loss at one year after the operation and serum level of albumin of in DFT group were 6.0±4.7kg and 4.11±0.29 g/dL, respectively and DST group were 7.6±5.3kg and 3.95±0.39 g/dL, respectively and there were no significance between two groups. Conclusions: DFT is superior to DST as a reconstruction method after PG in terms of suppressing GERD.
Reliability of endoscopic biopsy compared with endoscopic submucosal dissection histopathologic diagnosis.
Authors: Lee Kyuwon , Kim Tae Ho 
Published: January 2019

15 Background: Endoscopic biopsy is the most convenient and simple method for approaching gastric neoplasm. Aim of our study was to determine the diagnostic accuracy of biopsy during screening endoscopy compared to endoscopic submucosal dissection (ESD). Methods: 175 patients who underwent both screening endoscopic biopsy and ESD from 2015.01 to 2017.12 in Bucheon St. Mary’s hospital were retrospectively reviewed. Results: Seventeen lesions had different histopathological ESD findings compared with endoscopic biopsy. Among six endoscopic biopsies that showed atypia, four were diagnosed with adenocarcinoma and two maintained the results. 64 out of the 175 lesions showed low grade dysplasia by endoscopic biopsy. After ESD, two cases were diagnosed with high grade dysplasia and two cases were diagnosed with adenocarcinoma. Of 12 lesions which showed high grade dysplasia on endoscopic biopsy, four lesions turned out to be adenocarcinoma (three well differentiated, one moderately differentiated) after ESD. Of 91 adenocarcinoma lesions on endoscopic biopsy, three lesions had discrepancy on differentiation level and one lesion turned out to be signet ring cell carcinoma after all. Patients who were infected with Helicobacter pylori (H. pylori) had tendency to have discrepancy between initial biopsy and ESD histopathology result. (OR 3.68, 95% CI 1.08-11.955, P = 0.018). Conclusions: Discrepancy between endoscopic biopsy and post-ESD histopathology were found. Possibility of coexistence or progression to high grade neoplasm should be considered regarding endoscopic biopsy results especially if infected with H. pylori and active ESD histopathological confirmation needs to be done if necessary.
Predictive biomarkers for the efficacy of nivolumab as ≥ third-line therapy in patients with advanced gastric cancer (AGC): From a subset analysis of ATTRACTION-2 phase III trial.
Authors: Kim Jwa Hoon , Ryu Min-Hee , Park Young Soo , Ma Jungeun , Lee Sun Young , Kim Deokhoon , Kang Yoon-Koo 
Published: January 2019

152 Background: ATTRACTION-2 phase III trial proved the clinical efficacy of nivolumab (Nivo) in AGC patients (pts) treated with ≥ 2 previous chemotherapy regimens. However, the benefits of Nivo seem to be limited to a subset of pts and there is a need to identify predictive markers to select pts who would benefit from Nivo. Methods: Clinical data and tumor samples of AGC pts enrolled from Asan Medical Center in ATTRACTION-2 study were retrospectively analyzed. PD-L1 (+) was defined as combined positive score of ≥ 1%. EBV and MSI status were determined by EBV-encoded small RNA in situ hybridization and IHC for MLH-1, MSH-2, PMS-2, and MSH-6, respectively. Tumor mutation burden (TMB) was acquired by targeted next-generation sequencing using the NextSeq platform with OncoPanel. Results: A total of 45 pts (28/17 in Nivo/placebo arms) were eligible for the analysis. Baseline neutrophil-lymphocyte ratio (NLR) was median 2.9 and 7 pts had hyponatremia ( < 135). In 36 pts with available tissues, there were PD-L1 (+) (N = 13, 36.1%), EBV (+) (N = 6, 16.7%), and no MSI-high. TMB data could be acquired in 29 pts and median TMB was 8.2/Mb (0.0-21.3). With a median follow-up of 28.3 months (mo) in surviving pts, objective response rate, median progression-free survival (PFS), and overall survival (OS) were 16.7%, 1.6 mo, and 8.1 mo in Nivo arm and 0%, 1.6 mo and 6.5 mo in placebo arm. In Nivo arm with measurable lesions, PD-L1 (+) pts had significantly higher disease control rate than PD-L1 (-) pts (87.5% vs. 20%, p = 0.015). In multivariate model adjusted for important factors (age, sex, Nivo vs. placebo, treatment line, NLR, Na, and PD-L1), NLR ≤ 2.9 and PD-L1 (+) were significant factors for PFS (Hazard Ratio [HR] 0.47, p = 0.037 and HR 0.32, p = 0.006, respectively) and PD-L1 (+) was a significant factor for OS (HR, 0.44, p = 0.012). With adjusting these factors with TMB, PD-L1 (+) remained favorable for PFS and OS. Pts with NLR ≤ 2.9 or PD-L1 (+) or Na > 135 significantly favored Nivo compared to placebo in terms of PFS and OS. Conclusions: Baseline NLR and PD-L1 status may be relevant predictive markers to select pts with AGC who would benefit from Nivo.
The real-world data in patients with advanced gastric cancer treated with ramucirumab combination chemotherapy.
Authors: Kimura Akie , Sakai Daisuke , Kudo Toshihiro , Nishida Naohiro , Katou Aya , Inagaki Chiaki , Otsuru Toru , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Doki Yuichiro , Mori Masaki , Satoh Taroh 
Published: January 2019

156 Background: Ramucirumab with paclitaxel or ramucirumab monotherapy have shown the efficacy and safety in second-line chemotherapy for advanced gastric cancer. The previous reports have shown that neutrophil-lymphocyte ratio (NLR) was the prognostic factor for progression free survival. Methods: We conducted a retrospective review of clinical data from patients treated with ramucirumab at our institution between April 2015 to August 2018. Results: Of 90 patients, 81 received ramucirumab plus paclitaxel, and 9 received ramucirumab monotherapy. There was a significant difference of treatment line between combination therapy and monotherapy (mean 2.5 vs. 3.9, p = 0.00127). Response rate among the patients with target lesions was 18.8% (13/69), and disease control rate was 62.3% (43/69). On the other hand, response rate among the patients previously treated with nivolumab or pembrolizumab was 57.1% (4/7). Median overall survival (OS) for combination therapy and monotherapy was 10.8 months (95% confidence interval [CI] 7.1-11.9) and 5.5 months (95% CI 0.89-9.5), respectively. Grade 3 or 4 neutropenia was more common with combination therapy than with monotherapy (53.1 vs. 11.1%). Of 69 patients who received ramucirumab plus paclitaxel as second or third-line chemotherapy, high NLR (> 3) was the significant factor for poor PFS (median PFS, 2.7 vs. 5.4 months, p = 0.00103), but didn’t show the difference about OS (median OS, 9.7 vs. 11.9 months, p = 0.27). Conclusions: In our analysis, efficacy data was comparable with previous reports. In subgroup analysis, good response was observed in the group of prior nivolumab or pembrolizumab. NLR was prognostic factor for PFS, while it wasn’t show the relevance to OS because of the influence of after ramucirumab therapy.
Exploration of patients with gastric cancer who benefit from apatinib: An updated real-world study.
Authors: Sun Guo-ping , Li Dongliang , Ning Zhongliang , He Yifu , Zhang Fenglin , Chang Jiacong , Cheng Yunsheng , Yu Changjun , Peng Wanren , Hu Bin , Xia Liming , Jiang Congqiao , Wang Zi'an , Zhao Yong , Du Yingying , Wang Guihe , Zhang Nianqing , Liang Hui , Wang Daoqin , Hu Wenjun 
Published: January 2019

161 Background: A real-world study to observe the efficacy and safety of apatinib treatment in clinical practice, and explored patients (pts) who could benefit from apatinib. Methods: This is an open-label, prospective, observational study, pts (age ≥ 18 yrs) with pathologically or histologically diagnosed GC who were given apatinib treatment met the inclusion criteria. Results: From September 1, 2017 to September 1, 2018. 954 pts were enrolled. 679 pts received palliative treatment were included in the analysis. 499 (73.6%) were males. The age of the pts was (63.1 ± 10.8) yrs. Pts with ECOG PS 0/1 accounted for 78.1%. Pts received first-line treatment, second-line treatment, third-line treatment or above , respectively were 42.2%, 30.5%, 27.3%. 509 (75.1%) pts were treated with apatinib at dose of 500 mg. There were 375 pts available for efficiency evaluation. Among them, 1 achieved CR, 35 achieved PR, 198 had SD, and 57 had PD, resulting in an ORR of 11.9% and a DCR of 77.4%. The mPFS is 4.2 m (95% CI: 3.5-4.8), OS data was still in follow-up. This study showed its efficacy for pts with monotherapy compared with combined chemotherapy (3.3 m vs. 5.0 m, P = 0.003). The mPFS for patients with hypertension were longer than without hypertension (7.1m vs. 3.7m, P = 0.038). And pts also had longer mPFS with good ECOG PS (0-1) compared to those with poor ECOG PS (2-4) (4.7 m vs. 2.9 m, P = 0.003). The incidence of AEs was 402 (88.2%) and the grade 3/4 treatment-related AEs was 14.7%. The most common treatment-related AEs were debilitation (31.2%), hand-foot syndrome (27.5%), hypertension (25.3%), anorexia (11.5%), diarrhea (10.3%), albumin decreased (38.5%), uric acid elevated (31.6%), and total bilirubin increased (29.1%). Conclusions: In the real world, apatinib is confirmed to be effective and safe for GC pts. Factors associated with better prognosis were apatinib combined chemotherapy, ECOG PS 0/1 and occurrence of hypertension. Further analysis is needed to identify pts who benefit from apatinib treatment. Preliminary results of the study were released in ESMO 2018 Congress (683P). Clinical trial information: NCT 03333967.