bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric carcinoids: Does type of surgery or tumor affect survival?
Authors: Crown Angelena , Kanji Zaheer S. , Lopez-Aguiar Alexandra G , Dillhoff Mary , Poultsides George A. , Makris Eleftherios , Idrees Kamran , Marincola Smith Paula , Nathan Hari , Beems Megan , Weber Sharon M. , Fisher Alexander V , Fields Ryan , Davidson Jesse , Maithel Shishir , Rocha Flavio G. 
Published: January 2019

139 Background: Gastric carcinoids are rare neuroendocrine tumors of the GI tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. Methods: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000-2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection LR or formal gastrectomy FG). Clinicopathological parameters, recurrence-free (RFS), and overall survival (OS) were compared between groups. Results: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) had R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045). Conclusions: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.
The clinical analysis of thromboembolism in esophagogastric cancer in Japan: A single institute experience.
Authors: Oguri Tomoyo , Takahari Daisuke , Ota Yumiko , Osumi Hiroki , Nakayama Izuma , Wakatsuki Takeru , Ogura Mariko , Ichimura Takashi , Suenaga Mitsukuni , Shinozaki Eiji , Chin Keisho , Yamaguchi Kensei 
Published: January 2019

14 Background: Although patients with esophagogastric cancer have a higher risk of thromboembolism (TE), the clinical characteristics of esophagogastric cancer patients with TE remain unclear. Methods: We conducted a retrospective study of who were treated for TE in our institution from January 2014 to August 2017. Results: During this period, 1538 esophaogastic cancer patients received anti cancer therapy. Of these 62 (4.0%) patients diagnosed as having TE during their clinical course. Background of these patitents were median age :64.5 (28-87), gender male/ female: 36 /26, 47 had gastric cancer, 12 esophageal cancer, and 2 gastroesophageal cancer. Performance Status were 0/1/2/3 = 21/24/13/4. Clinical stage were Ⅳ 32 (metastatic sites; lymph nodes 7, peritoneal dissemination 6, ovary 4, liver 1), recurrence 18, and other 12 respectively. 26 patients did not have medical history, 15 had hypertension, 4 had diabetes mellitus, and 4 had hyperlipidemia. Pathologically, adenocarcinoma 50, squamous carcinoma 10, and other 2. Among patients with gastric cancer, 6 (12.8%) showed Her2 overexpression. The median D-dimer levels was 4.81(0.42-17.25) μg/ml. The onset of TE was before starting chemotherapy in 8(12.9%), during receiving chemotherapy in 48(77.4%), and during washout period in 6. On patients who developed TE during receiving chemotherapy, the regimens of chemotherapy were S-1 16, weekly paclitaxel 10 (plus ramucirumab 3), SOX 7, FP 4, Irinotecan 3, SP 3, FOLFOX 3, XP+Trastuzumab3, and others 9. The types of venous thrombosis were deep vein thrombosis 33, pulmonary embolism 23, central venous catheter 7, internal jugular vein 5, subclavian vein 4, and others 5. Four patients suffered cerebral infarction due to thrombosis of the arterial system thrombosis. Initial anticoagulation treatment for TE were heparin 33, warfarin 13, edoxaban 12 and other 4. 29 patients (46.8%) had no symptom related TE. Conclusions: In our analysis, 12.9% patients had TE before starting treatment, we should pay attention to TE immediately after diagnosis of esophagogastric cancer. As 46.8% patients have no symptom related TE, it is important to develop of biomarkers for screening TE, likely D-dimer.
Optimal surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy.
Authors: Hagi Takaomi , Kurokawa Yukinori , Miyazaki Yasuhiro , Takahashi Tsuyoshi , Tanaka Koji , Makino Tomoki , Yamasaki Makoto , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro 
Published: January 2019

141 Background: Surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy (NAC) has not been established yet. To determine the most optimal surrogate endpoint, we compared the validity of outcomes according to the endoscopic or histological response criteria and other histological factors in gastric cancer patients who underwent NAC. Methods: The target population in this study was 77 gastric cancer patients who underwent NAC followed by curative gastrectomy between January 2010 and December 2016. In histological response criteria, if necrosis or disappearance of the tumor was present in more than 2/3 of the primary lesion, the case was diagnosed as a histological responder. Hazard ratio (HR) for RFS in responders according to each factor was estimated, and survival curves were compared between responders and non-responders using log-rank test. Results: The number of patients in each regimen was as follows: docetaxel/cisplatin/S-1, 40; docetaxel/oxaliplatin/S-1, 16; cisplatin/S-1, 15; S-1/oxaliplatin, 4; docetaxel/S-1, 2. The endoscopic and histological response rates were 73% (56/77) and 16% (12/77), respectively. The proportions of patients with ypT0-1 and ypN0 were 17% (13/77) and 23% (18/77), respectively. HRs were 0.761 (log-rank p = 0.43) in the endoscopic response criteria, 0.879 (log-rank p = 0.77) in the histological response criteria, 0.703 (log-rank p = 0.46) in ypT0-1, and 0.121 (log-rank p = 0.001) in ypN0, respectively. Three-year RFS rates in ypN status were ypN0/1/2/3 = 93%/48%/43%/14%. Conclusions: Pathological ypN status was the most optimal surrogate endpoint of RFS for gastric cancer patients undergoing NAC. Patients with ypN0 would be expected for long relapse-free survival.
Effects of apatinib dose interruptions on safety and efficacy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting.
Authors: Wang Junsheng , Qin Shukui , Li Jin , Deng Wenying , Wen Lu , Zhang Guifang , Zhong Haijun , Jia Tongfu , Yang Jianwei , Bai Yuxian , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Ba Yi 
Published: January 2019

142 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]
Association of radiomics and outcome in esophageal cancer following neoadjuvant chemo-radiation.
Authors: Eaford India , Rishi Anupam , Zhang Geoffrey , Viera Alexander , Latifi Kujtim , Frakes Jessica M. , Pimiento Jose Mario , Fontaine Jacques-Pierre , Hoffe Sarah E. 
Published: January 2019

146 Background: Radiomic data extraction from medical images has the potential to differentiate tumor phenotypes. We investigated the potential of esophageal cancer radiomic features to differentiate clinical outcomes following neoadjuvant chemoradiation (NACRT). Methods: We retrospectively reviewed 68 biopsy-proven mid-distal esophageal/gastroesophageal junction (GEJ) cancer patients treated from 2007-2014 with NACRT followed by esophagectomy on an IRB approved study in which patients were eligible if imaging was performed at our institution. The primary tumor was segmented on baseline computed tomography (CT) and 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scans with contour review by two independent radiation oncologists. A total of 126 quantitative 3-D shape and intensity-based radiomics features were extracted using in-house data algorithm software. Locoregional control (LRC), metastasis free survival (DFS), metastasis free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and multivariate Cox proportion hazard. Results: Estimated actuarial 5-year RFS, LRC, MFS, OS was 56.6% (mean: 67.8 months, 95% CI 53.7-81.8 months), 83.1% (mean: 92.8 months, 95% CI 81.4-104.2 months), 64.9% (mean: 76.4 months, 95% CI 62.2-90.7 months), 39.5% (median survival 40 months, 95% CI 24.59-55.40), respectively. Pathological complete response (pCR) was achieved in 34 (50%) patients. Tumor Regression Grade (TRG) 0-1 indicative of complete response was associated with improved LRC [p = 0.04; Hazard Ratio (HR) 4.24 (1.01-19.01)]. On univariate analysis, 16 PET-based and 14 CT-based radiomics features were found to independently predict pCR. On multivariate analysis (MVA), three PET-CT based radiomic features [sphericity (p = 0.04), compactness (p = .05) and PET_TGV (p = 0.08)] were found to closely predict pCR. When grouped by median, PET sphericity independently predicted RFS [p = 0.014; Hazard Ratio (HR) 0.31 95% Confidence Interval (CI) 0.11-0.83]. Conclusions: This study suggests pre-treatment radiomic features in esophageal cancer may be prognostic for response assessment (pCR) and overall outcome following NACRT.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for nonresectable peritoneal carcinomatosis from gastric cancer.
Authors: Alyami Mohammad , Bonnot Pierre Emmanuel , Villeneuve Laurent , Bakrin Naoual , Glehen Olivier ,   BIG-RENAPE Working Group
Published: January 2019

149 Background: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate survival and postoperative outcome of PIPAC in patients with non-resectable PC from gastric cancer. Methods: This is a retrospective analysis. Sixty-nine PIPAC were applied in 22 consecutive patients pretreated non-resectable PC from gastric cancer. All patients had undergone previous lines of systemic chemotherapy (median, two lines). Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 37 °C and 12 mmHg at 6-week intervals.The treatment schedule proposed alternating 2 systemic chemotherapy followed by 1 PIPAC cycles. Outcome criteria were survival, adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of the first PIPAC, the median PCI was 18 (1-35). Median consecutive PIPAC cycles were 4 (1-9). Survival time was 19.5 months. Major complications (CTCAE - III, IV) occurred for 6 PIPAC (8.7%) and 1 (4.5%) patients died within 30 days of the PIPAC procedure a cause related to aspiration pneumonia during the general anesthesia. Systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (7-28). Conclusions: PIPAC with low-dose cisplatin and doxorubicin was safe and feasible in association with systemic chemotherapy. Survival data are encouraging and justify further clinical studies in this indication.
Next-generation sequencing to identify predictors of survival after trimodality therapy for esophageal cancer.
Authors: Oh Patrick , Zhang Minsi , Brady Paul , Sihag Smita , Molena Daniela , Ilson David H. , Janjigian Yelena Yuriy , Ku Geoffrey Yuyat , Wu Abraham Jing-Ching 
Published: January 2019

153 Background: Tumor mutation profiling has changed the prognostication and treatment of a wide variety of malignances. However, little is known about whether mutation profiles affect outcome in localized esophageal cancer treated with multimodality therapy. SMAD4 is a gene involved in the regulation of the TGF-β signal transduction pathway by negatively controlling the growth of epithelial cells and has been implicated as a prognostic factor in pancreatic cancer. We undertook an exploratory analysis of tumor mutation profiles, including SMAD4 status, in localized esophageal cancer patients treated with trimodality therapy at our institution. Methods: We identified 66 Stage II-III esophageal cancer patients treated with chemoradiation followed by surgery who had some form of tumor mutation profiling available. Only patients with mutation profiling from pre-treatment biopsy or post-chemoradiation surgical specimen (i.e. not from a subsequent metastatic lesion) were included. Twenty-two patients underwent next-generation sequencing assessing 341 candidate genes via targeted sequencing. Log-rank test was used to assess correlation of mutations to overall survival, and to pathologic response. Results: The median follow-up was 17.1 months. SMAD4 loss was identified in 3 of 22 patients (13.6%) who underwent next-generation sequencing, and was significantly associated with inferior overall survival (p=0.023). No other candidate genes were significantly associated with survival, and no genes were significantly associated with pathologic response. Conclusions: To our knowledge, this is the first analysis of next-generation mutation profiling and outcome in non-metastatic esophageal cancer patients treated with trimodality therapy. Due to the limited numbers, this was an exploratory analysis only. We identified SMAD4 loss as a potential adverse prognostic factor for survival. More next-generation sequencing data from non-metastatic esophageal cancer patients treated with multimodality therapy is needed to further elucidate the potential relationship of SMAD4 loss or other mutations with outcome.
Phase Ib study of ramucirumab and irinotecan for metastatic gastric cancer previously treated with fluoropyrimidine with/without platina and taxane.
Authors: Sagawa Tamotsu , Satake Hironaga , Fujikawa Koshi , Hatachi Yukimasa , Yasui Hisateru , Kotaka Masahito , Kato Takeshi , Tsuji Akihito 
Published: January 2019

155 Background: Optimal salvage line chemotherapy for previously heavily treated advanced/ metastatic gastric cancer (AGC) is unknown, but treated with irinotecan in Japan. Ramucirumab, a human IgG-1 monoclonal antibody that targets the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. Furthermore, combination chemotherapy with ramucirumab and irinotecan based regimen (FOLFIRI) is recognized as one of the promising regimens for metastatic colorectal cancer. To date, however, use of the ramucirumab plus irinotean regimen for AGC patients has not been investigated, and recommended doses (RD) of ramucirumab plus irinotecan for patients with AGC therefore remain unknown. The aim of this study was to determine the maximum tolerated dose (MTD) and RD for systemic chemotherapy with rumucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platina and taxane. Methods: Patients received systemic chemotherapy with ramucirumab (8mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150mg/m2). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606). Results: Six patients were enrolled from August 2015 to September 2017. MTD was not reached at level 1. Irinotecan 150 mg/m2 in combination with ramucirumab 8mg/kg could be administered with acceptable toxicity, and all patients were treated at these doses. No DLT was observed at Level 1. No treatment-related death was observed. Adverse events of grade 3/4 were neutropenia (17%), anemia (17%), hyponatremia (17%), hypertension (17%). Five of the six patients were evaluable for efficacy based on the RECIST criteria, and response rate and disease control rate were 20% and 100%, respectively. Conclusions: Salvage chemotherapy with a ramucirumab plus irinotecan regimen was well tolerable for patients with previously heavily treated AGC. RD was defined as ramucirumab 8 mg/kg in combination with irinotecan 150 mg/m2/day. Clinical trial information: 000018606.
Simulation study of volumetric modulated arc therapy for thoracic esophageal cancer using automated-radiotherapy planning software.
Authors: Murakami Yuji , Nagata Yasushi , Kimura Tomoki , Nishibuchi Ikuno , Nakashima Takeo 
Published: January 2019

158 Background: To prevent cardiac toxicity after chemoradiotherapy for esophageal cancer (EC), decrease of high irradiation dose to the heart without expanding the volume of lung irradiated low dose is needed, but this is not easy under the conventional techniques. Purpose of this study is to investigate the utility of volumetric modulated arc therapy using automated-radiotherapy planning software (auto-VMAT) to solve this issue. Methods: In this simulation study, data of 12 patients with stage I-III ECs previously treated by 3D-conformal radiotherapy (3DCRT) was used. We performed auto-VMAT planning using commercially available ‘Pinnacle3 Auto-Planning’ software. Targets for gross tumor (PTV1) and elective nodal region (PTV2), and organs at risk (OARs: lung, heart, left ventricle, epicardium, left pleura, liver and spinal cord) were delineated. Multi-portal beams were used for 3DCRT and dose description was 40 Gy in 20 fractions for PTV1+2 and 20 Gy in 10 fractions-boost for PTV1. We used the simultaneous integrated boost method for auto-VMAT with a dose description of 60 Gy for PTV1 and 48 Gy for PTV2 in 30 fractions. We performed planning in consideration with decrease of volumes irradiated middle to high dose in left ventricle and achievement of volume irradiated 5 Gy (V5) in lung < 50% as high-priority dose constraints. Results: Prescribed dose coverage of PTVs was equivalent between 3DCRT and auto-VMAT, while auto-VMAT showed better dose-conformity. Auto-VMAT showed a significant decrease of mean dose and V20-V60 in heart, left ventricle and epicardium and significant decrease of V50-V60 in lung and left pleura. V5 in lung was equivalent between 3DCRT and auto-VMAT (46.6±9.6% vs 45.6±4.7%; p = 0.72). Auto-VMAT achieved the V5 in lung < 50% in 10 among 12 patients and the max V5 in lung was 52.5%. Conclusions: Auto-VMAT for ECs achieved better dose conformity of targets, decrease of middle-high dose in heart, left ventricle and epicardium, and equivalent low dose volumes in lung. Auto-VMAT planning brings high quality dose distribution, uniformity of quality of planning, laborsaving and timesaving in treatment planning.
Body mass index and mortality in patients with gastric cancer: A large cohort study.
Authors: Lee Jung Hwan , Park Boram , Joo Jungnam , Kim Young-Il , Kim Chan Gyoo , Lee Jong Yeul , Choi Il Ju , Yoon Hong Man , Eom Bang Wool , Ryu Keun Won , Kim Young Woo , Cho Soo-Jeong 
Published: January 2019

16 Background: Although excess body weight has been known to be an important risk factor for mortality from many cancers including colorectal, endometrial and breast cancers, the prognosis of gastric cancer (GC) in obese patients seems controversial. Methods: We aimed to evaluate the association between body mass index (BMI) and mortality in GC in a large cohort. A single institute cohort of 7,765 GC patients undergoing curative gastrectomy between October 2000 and June 2016 were categorized into 6 groups; underweight (< 18.5 kg/m2), normal (18.5 to < 23 kg/m2), overweight (23 to < 25 kg/m2), obese I (25 to < 28 kg/m2), obese II (28 to < 30 kg/m2), and severely obese (≥30 kg/m2). The hazard ratios (HRs) for overall survival and disease-specific survival were calculated using Cox proportional hazard model. Results: We identified 1,279 all-cause and 763 disease-specific deaths among 7,765 patients, and the median follow-up period was 83.05 months (range, 1.02-186.97 months). In multivariable analyses adjusted by age, sex, tumor stage, comorbidity and operation methods, preoperative BMI was associated with all-cause mortality in a nonlinear pattern. As compared with patients who were normal weight, underweight BMI showed increasing mortality risk (hazard ratio (HR), 1.42, 95% confidence interval (CI), 1.15-1.77). In contrast, patients who were overweight (HR, 0.84; 95% CI, 0.73-0.97), obese I (HR, 0.77; 95% CI, 0.66-0.90) and obese II (HR, 0.77; 95% CI, 0.59-1.01) had lower risk of mortality. disease-specific mortality also had a similar pattern to overall survival showing the lowest mortality in obese II group (HR, 0.59; 95% CI, 0.40-0.88). There was no significant difference in severely obese patients in both all-cause and disease-specific mortalities. In spline analyses illustrated by a bell-shaped curve, risk for all-cause mortality was the lowest in patients with 26.67 kg/m2. Conclusions: Preoperative overweight and obese patients (23 to < 30 kg/m2) had lower all-cause and disease-specific mortalities compared to those with normal weight in GC patients who underwent curative surgical resection.