bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the extent of gastric resection on advanced gastric cancer treated with systemic chemotherapy.
Authors: Sasaki Yusuke , Watanabe Yutaka , Ohkita Ichiro , Hirota Jojo , Konno Jun 
Published: March 2017

194 Background: In previous clinical trials of adjuvant chemotherapy for gastric cancer, severe toxicity and discontinuation of chemotherapy was more common in patients receiving total gastrectomy (TG) than in those with distal gastrectomy (DG). However, data on the significance of the extent of gastric resection for stage IV gastric cancer treated with systemic chemotherapy are not available. Methods: This is a retrospective review of patients who were received chemotherapy with S-1 and cisplatin for stage IV gastric cancer at our institution between June 2009 and August 2015. The patients were classified into three groups according to the extent of gastrectomy (TG, DG and no gastric resection (NG)) before chemotherapy. Patient characteristics, survival and toxicities of chemotherapy were compared between three groups. Results: Among the 83 patients, 24 underwent TG, 19 DG, and 40 NG. Patient characteristics were well balanced between three groups. There was no significant difference in the requirement for dose reduction between TG, DG and NG patients (29% vs 11% vs 20%, respectively, p= 0.32). However, the rate of discontinuation because of toxicity was significantly higher in TG than in DG or NG patients (46% vs 16% vs 25%, respectively, p= 0.04). The main reasons of discontinuation were anorexia (43%), myelosuppression (23%), nausea (18%) and diarrhea (16%). The median progression-free survival was 8.9, 6.1 and 5.3 months ( p= 0.25), and the median overall survival was 16.0, 16.0 and 9.8 months ( p= 0.40) in the patients with TG, DG and NG, respectively. Conclusions: There was a high frequency of discontinuation of systemic chemotherapy in the advanced gastric cancer patients who underwent TG, but it was not associated with prognosis.
Recurrence patterns in esophageal cancer patients undergoing curative trimodality therapy.
Authors: Chan Edwin , Vanderwater Catherine , Woo Rachel , Cho Charles , Wong Jason , Xu Wei , Zhang Qihuang , Liu Geoffrey , Zhang Beibei , Cheung Agnes , Lee Alex , Chacko Pravin Philip , Fadhel Ehab , Kassam Zahra 
Published: March 2017

195 Background: To document pattern of recurrence and its relationship to the radiation treatment volume in esophageal cancer patients treated with trimodality therapy. Methods: Patients with adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus, T1-4N0-3 (AJCC 7thEd.) treated with chemoradiation (CRT) and esophageal resection between June 2010 and November 2015 participated in a prospective cohort study. Patients were planned using 4DCT and IMRT or VMAT. GTV and CTV were contoured on 4D exhale, inhale phases and voluntary exhale helical CT. CTV margins were 3-4cm superiorly and inferiorly, and 1cm circumferentially. CTVs were combined to form the ITV. PTV margin was 0.5cm. Site of first disease recurrence was classified as in-field (within 90% isodose), marginal (between 50-90%), or out-of-field (outside 50%). Results: Fifty-eight patients participated. Median age was 66 years (range: 40–78); 52 males: 6 females. 49 had adenocarcinoma, 7 SCC, and 2 mixed histology. 52 (90%) had clinically node positive disease. 31 received concurrent radiation 45-50Gy/25fr with Cisplatin/5FU and 27 received 41.4Gy/23fr with Carboplatin/Paclitaxel (CROSS protocol). 15 (27%) achieved a pathological complete response (pCR). Median follow up was 1.6 years (range: 0.2-4.8), 2-year overall survival 71%, disease-free survival 59%, median survival 4.4 years and median time to relapse 2.3 years. 17 patients (29%) had disease recurrence of which, at initial diagnosis, all were clinically node positive and 3 had pCR after CRT. Five developed locoregional recurrence (2 anastomatic, 3 locoregional nodes), 4 both locoregional and distant, and 8 distant recurrence alone. Of 9 patients with locoregional recurrence, 1 had in-field, 6 out-of-field and 2 had disease traversing in and out-of-field areas. 4 of 17 (24%) were treated with curative intent (1 surgery, 3 CRT) and all were alive at the latest follow up (time from first recurrence: 6 to 49 months). Conclusions: Survival and recurrence outcomes in this small cohort are similar to those reported in the literature. Only a small proportion of patients experienced in-field relapse. Of those who relapsed, 24% received curative salvage therapy.
Retrospective study of ramucirumab in patients with advanced gastric cancer.
Authors: Sakai Daisuke , Kudo Toshihiro , Kato Aya , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Yamasaki Makoto , Takiguchi Shuji , Mori Masaki , Doki Yuichiro , Satoh Taroh 
Published: March 2017

199 Background: Ramucirumab is a human, monoclonal antibody that specifically blocks activation of vascular endothelial growth factor (VEGF) Receptor. Ramucirumab with paclitaxel have shown the efficacy, and is recommended as second line chemotherapy in the gastric cancer treatment guideline in Japan. June 2015, ramucirumab was approved in Japan. Methods: We retrospectively investigated the efficacy and safety of ramucirumab in the patients with advanced gastric cancer in our institution from July 2015 to September 2016. Results: 50 patients were eligible. 11 patients were administered as ramucirumab monotherapy, and 39 patients were in combination with paclitaxel. 22 patients were administered as 2nd line treatment and 24 patients as third or more lines. Progression free survival and overall survival of all assessable patients was 2.4 months (95% CI: 1.8 - 4.6) and 6.0 months (95% CI: 4.6 - 9.2), respectively. PFS in subgroup of 2nd line and combined with paclitaxel (n = 20) was 7.0 months. Response rate in patients who had mesuarable lesion was 22.8 %. Major grade 3/4 adverse events were Leukopenia (59.1%), Neutropenia (68.2 %), febrile neutropenia (9.1%), and GI perforation (2.0 %). Conclusions: Ramucirumab seemed to be effective and safe in clinical setting against advanced gastric cancer.
A retrospective analysis of eye disorders induced by chemotherapy including S-1 for gastrointestinal cancer.
Authors: Yagisawa Masataka , Nakamura Michio , Matsuda Chika , Murai Taichi , Itaya Kazufumi , Sone Takayuki , Koike Yuta , Endo Ayana , Tsukuda Yoko , Ono Yuji , Nagasaka Atsushi , Nishikawa Shuji 
Published: March 2017

20 Background: Eye disorders (EDs) are common adverse events in patients received S-1 chemotherapy. Although there are some retrospective reports about EDs induced by S-1 mono therapy (mono) as adjuvant chemotherapy (Adj) in gastric cancer (GC), there are few reports about S-1 induced EDs in other gastrointestinal cancer (GIC). So we conducted this retrospective cohort study to investigate the incidence of S-1 induced EDs in GIC and the association with several clinicopathological factors, such as primary site, treatment setting, regimen, and duration. Methods: All the patients received S-1 chemotherapy for GIC in our institution from January 2008 to May 2016 were identified through medical records review extracted by our hospital data warehouse. We analyzed the incidence of S-1 induced EDs by reviewing all the medical records and the association between ED incidence and several clinicopathological factors using a chi-square test or a Fisher's exact test and logistic regression. Results: Two hundred eighty three GIC patients were analyzed on this study. Patients characteristics were as follows; male/female 170/113, GC/colorectal cancer (CRC)/pancreatic cancer (PC)/biliary cancer (BC) 119/67/57/32, non-Adj/Adj 263/20, S-1 mono/S-1 combination therapy (combo) 130/153. The overall incidence rate with EDs such as epiphora, gum, photophobia, nephelopsia was 15.2% (n = 43). The median time to onset of EDs was 109 days (range 5-1100). The each of ED incidence was 16.5% (n = 28) and 13.3% (n = 15) in male and female (p = 0.503), 14.8% (n = 39) and 20.0% (n = 4) in non-Adj and Adj setting (p = 0.520), 13.8% (n = 18) and 16.3% (n = 25) in S-1 mono and combo (p = 0.619), respectively. The incidence of EDs in GC, CRC, PC, and BC were 15.1% (n = 18), 17.9% (n = 12), 17.5% (n = 10), and 9.4% (n = 3) (p = 0.635), respectively. Conclusions: We found that the incidence of EDs induced by S-1 chemotherapy for GIC was relatively high regardless of cancer site, treatment regimen, setting and duration. Further accumulation of data as prospective cohort study is necessary to confirm the incidence of S-1 induced EDs. Clinical trial information: UMIN000024160.
Evaluation of hepatectomy, radiofrequency ablation, and transarterial chemoembolization for the local treatment of liver metastases in gastric cancer patients.
Authors: Chen Lin , Li Jiyang , Cui Jianxin , Xi Hongqing , Cai Aizhen , Zhang Kecheng , Gao Yunhe , Wei Bo 
Published: March 2017

200 Background: The optimal local treatment for liver metastases remains controversial. Except for hepatectomy, radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are both effective and low risk treatment modality with more expanded indications in patients with liver metastases. Thus, the aim of this study is to evaluate the efficacy of different methods for the local treatment of GCLM. Methods: From January 2006 to December 2015, 97 consecutive patients were eligible and included in a prospective database. They all received multidisciplinary treatments based on curative gastrectomy and local treatments (hepatectomy, RFA and TACE) for liver metastases. The 97 patients enrolled in a cohort study were divided into two groups, Group A (37 patients, curative hepatectomy with or without other local treatments) and Group B (60 patients, palliative RFA and/or TACE).The primary endpoints were overall survival (OS) and 5-year survival rate. Results: Baseline characteristics in the two groups were comparable. Correlation analysis found that interval time of metachronous, neutrophil to lymphocyte ratio and body mass index were not significantly linear associated with survival, with ρ = 0.051, ρ = 0.014 and ρ = 0.056, respectively. The overall survival time between the two groups were 94.1 months and 57.2 months, with 1-year, 3-year and 5-year survival rate 83.3%, 50.0% and 30.6% in Group A, respectively; and 83.7%, 28.6% and 18.4% in Group B, respectively (P = 0.049). Furthermore, subgroup analyses proved that among these three local treatments, hepatectomy was the most effective method (P = 0.014), with significantly difference from RFA (P = 0.001). Nevertheless, combination with RFA and/or TACE did not improve patients’ benefits (P = 0.062). And TACE has a similar (P = 0.227) efficacy with RFA, but significantly less costs. Conclusions: Hepatectomy is the optimal local treatment for liver metastases when the surgical R0 resection was intended. And it is not necessary to combine with other local treatments. As palliative local treatment, TACE is an acceptable method with relatively high cost-effective.
A proposal for a novel and simple TNM staging for gastric cancer.
Authors: Son Taeil , Sun Jiyu , Kim Hyoung-Il , Kim Jong Won , Cheong Jae-Ho , Choi Seung Ho , Noh Sung Hoon , Woo Yanghee , Fong Yuman , Park Sohee , Hyung Woo Jin 
Published: March 2017

21 Background: Current TNM staging system for gastric cancer has controversies regarding N classification. We aimed to develop a simple and novel TNM staging system for gastric cancer by re-grouping N classification. Methods: We retrospectively reviewed 14260 patients treated for gastric cancer. To develop simple combinations of TNM staging with similar weighted value between T and N classification, N classification was restructured with different cutoffs. The optimal cutoffs for the number of metastatic lymph node which maximize the x2 statistic of log-rank test for survival differences among patients were selected. C-statistic was used to compare the discriminating performance of the proposed N classification with the current N classification in the TNM staging system. We performed validation with 2 external datasets from a hospital in Korea (n = 1500) and SEER (n = 11324). Results: We identified the new cutoffs of N classification as 1~4, 5~10, 11~24, and 25 or more for N1, N2, N3a, and N3b, respectively. We found survival of the new N3b classification was similar to M1, regardless of T classification. Thus, we stratified these groups of N3b and M1 disease as stage IV, simultaneously. Our new TNM staging had similar weighted value between T and N classification resulting in simple combinations. (Table) Survival curves of subgroups in the new TNM staging had higher x2 value than current staging system (x2: 8239 vs. 7023, respectively) and homogeneity among subgroups in the same stage increased. However, C-statistics (0.801, 95%CI: 0.795, 0.807) of new model showed similar discrimination power than that (0.797, 95%CI: 0.791, 0.803) in 7th TNM staging system. C-statistics were also similar in other hospital in Korea (0.805 vs. 0.802, respectively) and SEER database (0.709 vs. 0.706, respectively). Conclusions: This novel staging system by recalculating cut-offs of N classification provides exceptionally simple and practical way to stratify substages in TNM staging for gastric cancer. [Table: see text]
Comparison of cisplatin induced nephrotoxicity with short hydration or conventional hydration in gastric cancer: A retrospective study.
Authors: Aoyama Takeshi , Kato Hiroki , Hagino Akane , Furutani Ryota , Ito Kazuyuki , Yoshioka Hidenori , Nakamura Masashi , Tunoda Takashi , Kawakami Kazuyoshi , Suzuki Kenichi , Ichimura Takashi , Yamaguchi Kensei , Hama Toshihiro 
Published: March 2017

211 Background: Cisplatin is administered in combination with massive and long term hydration to avoid renal toxicity. Although a short hydration protocol for cisplatin has been recently developed in lung cancer, which in gastric cancer has not been well clarified. We modified our XPT (capecitabine / cisplatin / trastuzumab) regimen, adopting short hydration method. This study was conducted to compare the preventive effect for renal toxicity of XPT therapy between the short hydration regimen and the conventional regimen. Methods: Medical records of patients with gastric cancer who received XPT therapy containing cisplatin at a dose of ≥ 80 mg/m2 were reviewed for 3 cycles of the observational period. Patients received either the short hydration regimen or the conventional regimen; short hydration regimen consisted of 2200 - 2500 mL of hydration over a period of 6.2 hours with furosemide and magnesium supplementation on day 1 and 1050 mL of hydration over 4 hours on day2 and 3, and the conventional regimen consisted of 3200 - 3500 mL of hydration over 24 hours on day 1 and 1550 ml of hydration over 6 hours on day2 and 3. Renal toxicity was then compared between the two groups. Results: Out of the total 31 patients, 6 received the short hydration regimen and 25 received conventional regimen. An elevated serum creatinine level ≥ grade 1 was significantly less frequent in the group receiving the short hydration regimen (0%, 0/6) than in the group receiving the conventional regimen (48.0%, 12/25) ( P < 0.05). The completion rate for the planned treatment in the short hydration group (100.0%, 6/6) was higher than that in the conventional hydration group (84.0%, 21/25). Conclusions: Based on the results of this study, short hydration may be a feasible regimen for XPT therapy in gastric cancer.
Development of follow up recommendations for completely resected gastroenteropancreatic neuroendocrine tumours (GEP-NETS): Practice Survey of Commonwealth Neuroendocrine Tumour Collaboration (CommNETS) in conjunction with North American Neuroendocrine Tumour Society (NANETS).
Authors: Singh Simron , Chan David Lok Hang , Moody Lesley , Carsley Sarah , Metz David C. , Strosberg Jonathan R. , Segelov Eva 
Published: March 2017

224 Background: Published guidelines for follow up after R0 resection of GEP-NETS are complex and emphasize closer surveillance in the first 3 years, as per other GI malignancies. NETS have a different pattern and timescale of recurrence, hence require more practical and tailored follow up. Aim: To examine real world follow up practices compared to published guidelines for follow up of patients with GEP-NETs. Methods: A detailed electronic cross-sectional survey was developed and distributed to members of the CommNETS Collaboration (Australia, NZ, Canada) and NANETs. Questions addressed demographics, knowledge and use of current guidelines and follow up practices relating to various prognostic factors. Descriptive statistics were obtained for all responses, stratified by country, patient volume and specialty. Results: There were 163 respondents: Australia: 59; NZ: 25; Canada: 46; US: 33. 50% were Medical Oncologists; 23% Surgeons; 13% Nuclear Medicine; 14% other. 38% of respondents were “very familiar” with NCCN NET guidelines; 33% with ENETS, 17% with ESMO, however only 15%, 27% and 10% found them “very useful”, respectively. 63% reported not using guidelines at their institution. Ranking of prognostic factors (top 5, decreasing order): grade, Ki67/mitotic count, T stage, N stage and site of origin. Follow up in 1st 2 years was most commonly every 6 months (62%); in years 3-5 every 12 months (59%) and > 5 years, 12 months (41%). Follow up patterns did not differ significantly by patient volume. The commonest investigations were CT scans (66%) and CgA (86%). When poor prognostic factors were introduced, increased visits and tests were recommended. Conclusions: This large international survey yields detailed information, highlighting variation in current follow up practices not well addressed by current guidelines. This forms a strong basis for the upcoming CommNETS/NANETS consensus meeting, which aims to produce user friendly, practical guidelines tailored to the expected pattern of recurrence in patients with NETs.
Correlation of phase 2 trials (Ph2t) results with outcomes of phase 3 trials (Ph3t) of investigational agents (IA) in locally advanced and metastatic pancreas cancer (LAMPC).
Authors: Tang Monica , Chen Julia , Goldstein David , Links Matthew , Lord Sally , Marschner Ian , Simes John , Lee Chee Khoon 
Published: March 2017

227 Background: There has been minimal improvement in treatment outcomes in LAMPC. We examined results of Ph2t and Ph3t to better understand potential reasons in order to improve future trial design. Methods: We conducted a systematic review of published Ph2t and Ph3t (1978-2015) of first-line treatment for LAMPC. Data for baseline characteristics and best objective response rate (ORR) were compared. Where possible, we compared outcomes for IA tested in Ph2t with corresponding Ph3t. Results: We identified 149 Ph2t with 180 treatment arms comprising 7499 participants. Ph2t were predominantly single-arm (83%) or multi-arms with different IA doses or combinations (5%). Only 12% were randomized studies with concurrent control. The median sample size was 42 (range 8-133). The pooled ORR was 13.8% (95% CI 13.0%-14.6%) but there was substantial heterogeneity (range 0-60%, Pheterogeneity < .001; I2= 75.9%). Although 56% of Ph2t concluded that IA should be considered for Ph3t, only 11% actually proceeded to Ph3t testing. Factors associated with Ph3t testing included absence of randomized design with concurrent control (12.2% vs 5.6%), higher proportion of performance status 0 patients (24.4% vs 21.7%), higher proportion of locally advanced disease only (23.4% vs 15.4%), and higher median ORR (22.0% vs 15.4%). Of 26% Ph2t that investigated novel biological IA, 92% had a potential predictive biomarker but only 1 trial was enriched for the biomarker. Only 8% of Ph2t with novel biological IA proceeded to Ph3t. ORR of IA tested in Ph2t correlated moderate poorly with ORR (r2 = 0.21) and 6 month progression-free survival rate (r2 = 0.26) in corresponding Ph3t. Only 3 IA in Ph3t demonstrated clinically meaningful improvements. Conclusions: Despite multiple Ph2t conducted over 4 decades, only 11% progressed to Ph3t, with 3 IA ultimately improving clinical outcomes. Ph2t results do not inform Phase 3 testing of IA. Potential reasons include patient heterogeneity, overly optimistic interpretation of Ph2t results, lack of concurrent control in Ph2t and ineffective agents. These issues should be addressed in order to improve success of future Ph3t in LAMPC.
Impact of direct-acting antiviral agents-induced SVR on the long-term burden of hepatocellular carcinoma in chronic hepatitis C cirrhosis.
Authors: Udompap Prowpanga , Mannalithara Ajitha , Kim Donghee , Kim W. Ray 
Published: March 2017

230 Background: Sustained virological response (SVR) has been associated with decreased morbidity and mortality from hepatitis C virus (HCV) infection. Data are sparse, however, about the long-term benefits of direct-acting antiviral agents (DAAs) in terms of risk reduction for hepatocellular carcinoma (HCC). We estimate the impact of SVR on the HCC incidence in the DAA era when SVR is achieved nearly universally even in patients with advanced fibrosis and cirrhosis. Methods: We constructed a Markovian model of 50-year-old patients with compensated HCV cirrhosis (n=1,000) to model the incidence of HCC over 20-years of follow-up. We compared 2 cohorts: 1) SVR following DAA therapy and 2) no SVR (natural history). In the latter, HCC would develop at an annual rate of 4.2% and patients would die as a result of end stage liver disease (ESLD) according to their MELD (=6 at baseline). In the former, MELD score would not increase, the HCC risk would decrease and, in some patients, cirrhosis would regress. Results: The table summarizes the 20-year outcome in the two cohorts. In the cohort without SVR, HCC would occur in 33% and 63% would die of ESLD. In the SVR cohort, the proportion of HCC would increase to 37% as the number of subjects at HCC risk would increase, as a result of a dramatic reduction in deaths from ESLD. In the univariate sensitivity analyses, the cumulative HCC incidence was mainly influenced by the rate at which the risk of HCC is decreased after SVR, followed by the change in cirrhosis regression rate. Conclusions: Although HCC risk would decrease after SVR in a given individual patient with cirrhosis, on the population level, highly effective DAA therapy may lead to a paradoxical increase in the burden of HCC. These data underscore the important of (1) HCC surveillance in patients with cirrhosis even after SVR and (2) DAA intervention before cirrhosis develops. [Table: see text]