bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes comparable between endoscopic resection and surgical resection for T1b esophageal adenocarcinoma.
Authors: Datta Samit Kumar , Belini Geoffrey , Singh Maharaj , Papenfuss Wesley Allan , Hernandez Lyndon , Sanchez Federico Augusto , Weese James L. , Chevinsky Aaron , Guda Nalini 
Published: January 2019

100 Background: Current guidelines recommend esophagectomy for submucosal T1b esophageal cancer. Data regarding efficacy of endoscopic resection (ER) of T1b esophageal cancer are limited. Our goal was to compare survival outcomes of ER as opposed to conventional surgical resection (SR) in a large cohort of patients with T1b cancers from a large national database. Methods: Data were obtained from the large national database maintained by the Commission on Cancer. Patients with T1b esophageal cancers with clinical stage 1A and 1B who underwent ER and SR between 2010 and 2014 were identified using the American Joint Committee on Cancer (AJCC Version 7). Patients undergoing ER and SR were identified. Patients who underwent neoadjuvant therapy or had incomplete survival data were excluded. The primary outcome was survival for age and Deyo-Charlson comorbidity index. We also evaluated 30-Day and 90-Day Mortality outcomes. Results: There were 1071 patients with T1b esophageal cancer with complete mortality data. After selecting and excluding patients above, 141 patients were identified who underwent EET and 286 who underwent esophagectomy. Average age was 71.5 years in the ER group and 64.5 years in the SR group (p < 0.001). In the group, 30-Day mortality after surgery was 1/134 (0.8%, 7 missing) compared to surgery with 30-Day mortality of 6/283 (2.1%, 3 missing) (P = 0.308). 90-Day mortality after surgery for the ER group was 3/134 (2.2%, 7 missing) compared with the surgery with 90-Day mortality of 11/281 (3.9%, 5 missing) (P = 0.377). Adjusted for age and Deyo-Charlson comorbidity index, there was a HR of 1.051 (95% CI 0.695-1.589, p = 0.815) for mortality associated with surgery compared with ER. Mean follow-up of 42.6 months for the ER group and 55.7 months for surgery group. Conclusions: Based on the data from a large national cancer data base ER seems to be comparable to SR in terms of short term (30 day and 90 day) mortality. Overall survival seems to be similar in both groups Prospectively done randomized studies comparing ER versus SR are desirable.
Endoscopic submucosal dissection versus surgery for undifferentiated-type early gastric cancer: A meta-analysis.
Authors: Kim Byung-Wook , Ma Dae Won , Kim Joon Sung 
Published: January 2019

111 Background: It is still controversial to treat undifferentiated early gastric cancer by endoscopic submucosal dissection (ESD). Therefore, we aimed to perform a meta-analysis to investigate long-term outcomes of ESD and surgery for undifferentiated early gastric cancer. Methods: PubMed, Cochran Library, and EMBASE were used to search for relevant researches comparing endoscopic submucosal dissection and surgery for undifferentiated early gastric cancer. The methodological quality of the included publications was evaluated using the Risk of Bias Assessment tool for Non-randomized Studies. The overall survival rate, recurrence rate, adverse event rate, and complete resection rate were explored, and the odds ratio (OR) and 95% confidence interval (CI) were estimated. Results: This meta-analysis enrolled five studies, with 376 and 1148 participants undergoing ESD and surgery, respectively. Overall survival rate did not show significant difference between ESD and surgery group (OR 0.57, 95% CI 0.18 – 1.83, P = 0.34). However, ESD was associated with higher recurrence rate (OR 11.57, 95% CI 5.07 – 26.39, P < 0.001) and lower complete resection rate (OR 0.03, 95% CI 0.01 – 0.11, P < 0.001). Adverse event rate was similar between two groups (OR 0.95, 95% CI 0.46 – 1.96, P = 0.88). Conclusions: Despite higher recurrence rate and lower complete resection rate, ESD demonstrated similar overall survival rate and adverse event rate in the treatment of undifferentiated early gastric cancer compared to surgery.
The efficacy of splenic hilar lymph node dissection in advanced gastric cancer.
Authors: Toriumi Tetsuro , Makuuchi Rie , Kamiya Satoshi , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: January 2019

112 Background: Total gastrectomy with splenectomy for splenic hilar lymph node (No.10 LN) dissection had been a standard treatment for proximal advanced gastric cancer in Japan. The efficacy of No. 10 LN dissection with splenectomy for advanced gastric cancer without the greater curvature invasion was denied by a randomized controlled trial, JCOG0110. However, JCOG0110 did not include the patients with greater curvature invasion. Therefore, we aimed to clarify the role of No. 10 LN dissection in patients with proximal advanced gastric cancer invading the greater curvature. Methods: A total of 273 patients with proximal advanced gastric cancer who underwent curative total gastrectomy with splenectomy from 2002 to 2013 were included. We reviewed esophagogastroduodenoscopy and upper gastrointestinal series for evaluation of clinical tumor localization and classified the patients into with greater curvature invasion group (G group, n = 108) or without invasion group (NG group, n = 165). The incidence and therapeutic value index (TVI) of No. 10 LN were compared between the groups. Results: Patients in the G group had more advanced T stage, undifferentiated histology, and larger tumor size than those in the NG group. However, there was no difference in survival between the groups; 5-year overall survival (5-OS) was 66.3% in the G group and 69.1% in the NG group (p = 0.570). The incidence of No.10 LN metastasis was significantly higher in the G group (10.2%) than that in the NG group (3.0%) (p = 0.028). TVI for No.10 LN dissection was higher in the G group (5.6) than that in the NG group (0.6). The survival of the patients with No.10 LN metastasis tended to be better in the G group, although it did not reach statistical significance (5-OS: 54.5% in G group vs. 20.0% in NG group, p = 0.336). Conclusions: It is suggested that splenic hilar LN dissection has a favorable effect on survival in patients with proximal gastric cancer invading the greater curvature.
Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A retrospective real world study.
Authors: Chen Yang , Dai Guanghai 
Published: January 2019

113 Background: Although the clinical trial WJOG7112G was failed to prove weekly paclitaxel with trastuzumab in patients with HER2-positive gastric or gastro-esophageal junction (GEJ) cancer refractory to trastuzumab is better than paclitaxel alone, there are limited data concerning efficacy of continuing trastuzumab beyond first-line progression in the real world. Methods: This retrospective study included all consecutive patients with HER2-positive advanced gastric or GEJ adenocarcinoma who received a chemotherapy with trastuzumab in first-line, or second-line, or third-line therapy between 2010 and 2016 in Chinese People’s Liberation Army General Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated from the initial chemotherapy. Results: A total of 67 patients (median age, 59 years; male, 71.6%) with HER-2 positive advanced gastric or GEJ adenocarcinoma treated with chemotherapy plus trastuzumab initially in first (n = 50), second (n = 13), or third (n = 4) line of therapy were included. The median OS of trastuzumab for initial first-line, second-line, or third-line treatment was 16.7 months, 14.2 months, and 13.2 months, respectively (P = 0.83). In patients initially using trastuzumab in first-line therapy, the continuation (n = 19) versus discontinuation (n = 31) of trastuzumab beyond first-line progression was significantly associated with an improvement of median PFS (3.4 versus 1.9 months; P = 0.02), but not OS (19.0 versus 16.4 months; P = 0.13). In the multivariate analysis including the ECOG PS, number of metastatic sites and chemotherapy regimen, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.77; 95% CI, 0.41-0.93; P = 0.04), but not OS (HR, 0.85; 95% CI, 0.56-1.22; P = 0.24). Conclusions: This study suggests that HER-2 positive advanced gastric or GEJ adenocarcinoma patients could benefit from trastuzumab no matter when they start receiving trastuzumab. The continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer for PFS, but not for OS. Large scale prospective randomized validation is warranted.
The preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma: A retrospective cohort study.
Authors: Takeuchi Masashi , Kawakubo Hirofumi , Mayanagi Shuhei , Irino Tomoyuki , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Kitagawa Yuko 
Published: January 2019

120 Background: Postoperative complications have a negative impact on overall survival after esophagectomy because systemic inflammation may induce residual cancer cell growth. A solution that could suppress micrometastasis is neoadjuvant therapy; however, to date, no study has shown that neoadjuvant therapy suppresses the proliferation of cancer cells due to postoperative complications after esophagectomy. To investigate the preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma. Methods: In total, 509 patients who underwent esophagectomy for primary esophageal squamous cell carcinoma were included in this retrospective cohort study. We investigated the relationship between complications, such as pneumonia, and long-term oncologic outcomes with and without neoadjuvant therapy. Results: Among all the patients, the 3-year overall survival (OS) rate was 68.4% and the disease-free survival (DFS) rate was 58.1%. The patients were categorized into two groups: the neoadjuvant therapy (+) group (n = 227) and the neoadjuvant therapy (−) group (n = 282). Among patients not undergoing neoadjuvant therapy, the patients with pneumonia, atrial fibrillation, pyothorax, or chylothorax had significantly poorer OS and DFS than patients without these complications. However, among patients undergoing neoadjuvant therapy, there were no significant differences in long-term outcomes, regardless of the presence of complications. In multivariate analyses, pneumonia (p = 0.014) and chylothorax (p = 0.006) were identified as predictors of death in the neoadjuvant therapy (−) group. Conclusions: In patients with esophageal squamous cell carcinoma, the negative impact of postoperative complications can be reduced by performing neoadjuvant therapy.
Pre-treatment pulmonary function testing as a predictor of cardiopulmonary toxicity in esophageal cancer patients treated with trimodality therapy.
Authors: Smith Na Lu , Hallemeier Christopher Leigh , Spears Grant M. , Halfdanarson Thorvardur Ragnar , Neben-Wittich Michelle A. , Harmsen William S. , Mahipal Amit , Blackmon Shanda H , Haddock Michael G. , Merrell Kenneth 
Published: January 2019

121 Background: We evaluated the role of pre-treatment pulmonary function testing (PFT) in predicting the likelihood of cardiac and/or pulmonary toxicity for esophagus cancer patients receiving trimodality therapy. Methods: From 2007 to 2013, 64 patients with esophageal cancer received trimodality therapy at a single tertiary center with pre-treatment PFTs. The odds ratio of pre-treatment PFT as a predictor of cardiopulmonary toxicity was assess with univariate analysis (UVA). FEV1 (forced expiratory volume in 1 second) and DLCO (diffusion capacity for carbon monoxide) were assessed per 0.5-unit decrease. Percent FEV1 and DLCO predicted were assessed per 10% decrease. Results: The median age was 62 years (range, 41-79) with 88% male patients. A total of 70% of patients had adenocarcinoma with 66% having stage 3 disease. Most patients were former (43%) or current smokers (32%) and 18% had COPD. One or more cardiac comorbidities were observed in 54% of patients. The median RT dose was 50 Gy and the most frequent concurrent chemotherapy was cisplatin/5FU (53%). The median pre-treatment FEV1 and DLCO was 2.8 liters (range, 1-4.9) and 22.5 mL/min/mmHg (range, 17.2-25.5), respectively. This correlated to a median percent predicted value for FEV1 and DLCO of 85% (range, 30-124%) and 81.5% (range, 49-119%), respectively. The overall rate of any cardiac and pulmonary toxicity was 35% and 50%, respectively. Percent predicted value of both FEV1 and DLCO was statistically associated with pulmonary but not cardiac toxicity (Table). Conclusions: Patients with compromised pre-treatment pulmonary function are at higher risk of developing post-treatment pulmonary toxicities. Pulmonary function testing should be routinely performed prior to initiation of trimodality therapy for patient risk stratification. [Table: see text]
Comparative effectiveness of nivolumab (NIVO) relative to standard of care (SOC) for advanced/metastatic (adv/met) gastric or gastroesophageal junction cancer (GC/GEJC): A simulated treatment comparison (STC).
Authors: Chau Ian , Ayers Dieter , Goring Sarah , Keeping Sam , Goulding Rebecca , Cope Shannon , Chamot Eric , Le Hannah , Xu Yanqing , Abraham Pranav , Korytowsky Beata 
Published: January 2019

128 Background: The prognosis of adv/met GC/GEJC among patients receiving third and later lines (L) of therapy is poor, and effective treatment options are limited. The study objective was to estimate the relative effect of NIVO versus SOC for overall survival (OS), in the US among adv/met GC/GEJC patients who received ≥ 3L therapy. Methods: A STC was performed using individual patient data from the single-arm CheckMate 032 (CM032) trial, and the Flatiron Health (FH) database. Eligible patients had adv/met GC/GEJC and received NIVO (CM032) or SOC (FH) as ≥ 3L therapy; all patients met CM032 eligibility criteria. A regression model of OS was fit to CM032 data using prognostic factors and treatment effect modifiers identified through a systematic literature review. The regression model was used to predict OS for NIVO, using Flatiron patient characteristics as covariates, and to estimate the expected outcome if NIVO had been available in the Flatiron population. The observed and predicted OS for NIVO was compared against the observed OS for SOC to generate naïve and adjusted hazard ratio comparisons of NIVO vs SOC. Results: In total, 42 and 43 patients were included from CM032 and Flatiron, respectively. In the Cox model, 19 prognostic factors were considered and the final model adjusted for 6, based on data availability across the two sources: ECOG, alkaline phosphatase (ALP) and hemoglobin, sex, prior surgery, and tumor location. Median OS was 8.97 months in the NIVO group and 5.61 months in the SOC group. The STC adjustment yielded a hazard ratio of 0.66 (95% CI: 0.41 to 1.06) for NIVO vs SOC compared to the naïve estimate of 0.64 (0.40 to 1.03). Sensitivity analyses confirm this result. Conclusions: In the absence of head-to-head data, this study suggests that NIVO may confer a benefit in terms of OS versus SOC for patients with GC/GEJC in ≥ 3L therapy in the US setting. Despite the inherent limitations of using non-randomized comparisons of clinical trial data and real-world evidence, these findings provide insight into the potential benefit of novel agents such as NIVO.
Phase I/II study of ramucirumab plus nivolumab in patients in second-line treatment for advanced gastric adenocarcinoma (NivoRam study).
Authors: Hara Hiroki , Shoji Hirokazu , Takahari Daisuke , Esaki Taito , Machida Nozomu , Nagashima Kengo , Aoki Kazunori , Honda Kazufumi , Miyamoto Takahiro , Boku Narikazu , Kato Ken 
Published: January 2019

129 Background: Nivolumab (Nivo) showed a survival benefit in salvage line of advanced gastric cancer (AGC) patients in ATTRACTION-2 trial. Based on synergistic anti-tumor effects by simultaneous blockade of PD-1 and VEGFR-2, this phase 1/2 study was conducted to investigate the safety and efficacy of Nivo plus ramucirumab (Ram) in the second line chemotherapy for AGC. Methods: AGC patients with measurable lesions, PS 0-1, disease progression on first line chemotherapy containing platinum were eligible. Patients received Nivo (3mg/kg, Q2W) and Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. After feasibility was evaluated in six patients (phase 1 part), additional 40 patients were required in a phase 2 part with the primary analysis (expected 6-months progression-free survival (PFS) rate of 36%, threshold of 18%, one-sided alpha level of 10%, power of 90%). Secondary endpoints included overall response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. Results: 46 AGC patients (median age 66 years, PS 1 40%) were enrolled. No dose limiting toxicities were observed in the phase 1 part. With median follow up time of 10.2 month, 6-month PFS rate was 37.4% (90% confidential intervals: 25.7-49.2%), which met the primary endpoint of the phase 2 part. ORR/DCR were 26.7%/62.2%. Median PFS/OS were 2.9/9.0 months. Among all enrolled patients, grade 3 or 4 treatment related adverse events were hypertension (n = 2), diarrhea (n = 2), perforation at jejunum (n = 1), hemorrhage (n = 1), colitis (n = 1), pancreatitis (n = 1), liver dysfunction (n = 1), cholangitis (n = 1), hematoma (n = 1), neutropenia (n = 1) and proteinuria (n = 1). There were no treatment-related deaths. Conclusions: Combination of Nivo and Ram showed promising antitumor activity and mild toxicity profile for second line AGC, which is worth evaluating in a further confirmatory study. Clinical trial information: NCT02999295.
Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy containing paclitaxel for advanced gastric cancer.
Authors: Otsuka Ryo , Iwasa Satoru , Yanai Takako , Shoji Hirokazu , Honma Yoshitaka , Okita Natsuko , Takashima Atsuo , Kato Ken , Hashimoto Hironobu , Makino Yoshinori , Sekiguchi Masatoshi , Ishizone Yoshimasa , Boku Narikazu , Yamaguchi Masakazu 
Published: January 2019

132 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of platinum and paclitaxel (PTX) persisting for long time. In the Gastric Cancer Treatment Guideline (Japanese Gastric Cancer Association, 2018), first-line chemotherapy with fluoropyrimidine plus platinum followed by taxane based chemotherapy is recommended. It is not well known how much CIPN by platinum in the first-line chemotherapy affect the tolerability of second-line chemotherapy containing PTX (second-PTX). Methods: The subjects were advanced gastric cancer patients who received second-PTX after the platinum-containing first-line chemotherapy between March 2015 and June 2018. Patients were divided into two groups according to prior platinum: oxaliplatin (prior L-OHP) and cisplatin (prior CDDP) groups. CIPN was graded according to CTCAE ver.4. Severity of CIPN, dose reduction and discontinuation due to CIPN during the second-PTX were compared between the two groups. Results: 109 patients (50 prior L-OHP group and 59 prior CDDP group) were included in this retrospective study. The severity of CIPN just before second-PTX was 46% for grade 1 and 12% for grade 2 in the prior L-OHP group, and 8.5% and 0% in the prior CDDP group. The initial dose of PTX was reduced in 59 % of the prior L-OHP and in 39 % of the prior CDDP group. The worst grade of CIPN during second-PTX was 40% for grade 1, 34% for grade 2, 14% for grade 3 in the prior L-OHP group, and 33.9%, 20.3%, 0% in the prior CDDP group. Median time to grade 2 neuropathy during second-PTX was 2.5 months in the prior L-OHP group and 8.6 months in the prior CDDP group (p = 0.0004). CIPN-related dose reduction of PTX were 12.0% in the prior L-OHP group and 3.4% in the prior CDDP group (p = 0.177). Discontinuation of second-PTX due to CIPN were 10.0% in the prior L-OHP group and 5.1% in the prior CDDP group (p = 0.541). Conclusions: The severity of CIPN and tolerability of the second-PTX may be affected by prior platinum, L-OHP or CDDP, in the first-line chemotherapy for advanced gastric cancer.
Tislelizumab in combination with chemotherapy for the treatment of Chinese patients (pts) with esophageal squamous cell carcinoma (ESCC): Results from one cohort of an ongoing phase 2 study.
Authors: Xu Nong , Yuan Xianglin , Wang Buhai , Bai Yu-Xian , Li En Xiao , Li Yanyan , Wang Huanli , Xu Jianming 
Published: January 2019

14 Background: Tislelizumab, a humanized IgG4 mAb with high affinity and specificity for PD-1, is specifically engineered to minimize binding to FcγR on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. This phase 2 study assessed the safety and tolerability of tislelizumab combined with chemotherapy as first-line therapy in pts with gastric cancer and ESCC; the results of the ESCC cohort are presented here. Methods: Chinese pts with inoperable, locally advanced ESCC were treated with tislelizumab (200 mg IV Q3W), cisplatin (80 mg/m² IV Q3W for up to six cycles), and fluorouracil (800 mg/m²/d, days 1-5 IV Q3W for up to six cycles). Safety/tolerability of the combination regimen was assessed by monitoring adverse events (AEs) per NCI-CTCAE v4.03 criteria. Results: As of 13 June 2018, 15 pts (median age, 61 yrs; male/female, 14/1) were enrolled. The median treatment duration was 108 days (range 21-201). The mean (Q1, Q3) dose intensity was 0.92 (0.91, 0.97) for tislelizumab, 0.91 (0.90, 0.98) for cisplatin, and 0.78 (0.72, 0.97) for 5-FU. Among 15 pts, AEs occurring in > 2 pts reported to be related to chemotherapy and/or tislelizumab are detailed in the table. One pt experienced grade 5 hepatic dysfunction (possibly from progressive disease and underlying hepatitis) which was possibly related to study treatment, according to the investigator. Four pts discontinued study treatment due to AEs (grade 3 tracheal fistula, grade 3 lung infection, grade 2 pneumonitis, and grade 3 increase in aspartate aminotransferase). The antitumor activity data remain unmatured and may be updated later. Conclusions: Tislelizumab combined with chemotherapy was generally well tolerated in pts with advanced ESCC. Clinical trial information: NCT03469557. [Table: see text]