bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of neoadjuvant epirubicin(E), cisplatin(C) and 5-fluorouracil(F) followed by chemoradiation with selective surgical resection/salvage for carcinomas of the esophagus and esophagogastric junction.
Authors: Poen Joseph C , Poen Joseph W , Gullion David S. 
Published: February 2017

84 Background: A subset of patients with local and regionally confined carcinoma of the esophagus (ES) or esophagogastric junction (EGJ) will not benefit from esophagectomy or esophagogastrectomy. Examples include medical inoperability and confined disease that is technically unresectable (T4 and/or N2-3). With that in mind we undertook to optimize the non-operative component of ES and EGJ cancer treatment, with surgery reserved for selected cases (medically fit, limited stage, suspicion of residual or recurrent disease). Methods: Eligible patients had AJCC stage T2-4,N0-3,M0 squamous or adenocarcinoma of the esophagus or esophagogastric junction. Medically inoperable patients were included if fit for ECF and chemoradiation (CRT) and regional disease could be encompassed within extended radiation fields. E (50mg/m2), C (60mg/m2) were given days 1,22 with F (200mg/m2) days 1-42 by protracted infusion. Subsequent CRT was C (100mg/m2) days 49,70 and F (200mg/m2) days 49-91 with 54 Gy in 30 fractions over 6 weeks. Complete responders by PET and biopsy received 2 additional cycles of ECF. Results: Between 2003 and 2015, 40 patients with non-metastatic squamous (n = 13) and adenocarcinoma (n = 27) signed informed consent. Most had clinical stage T3-4 (78%), positive regional lymph nodes (58%) and/or were felt to be inoperable due to medical comorbidities or advanced disease (50%). Dose reductions were allowed for grade II-III toxicity during ECF (13%) and CRT (33%). There was one treatment-related death (3%). At a median follow-up of 5 years, 10 patients (25%) have undergone esophagogastrectomy for persistent or recurrent disease. Median overall survival (OS) is 46 months. Survival at 1,3,5 and 7 years is 82%, 53%, 44% and 35% respectively. Conclusions: In local/regionally confined ES and EGJ cancer, long term survival with acceptable toxicity can be achieved with neoadjuvant ECF and CRT followed by selective surgical resection/salvage. This strategy appears to be appropriate for medically inoperable and technically unresectable cases, and can be considered for operable cases as well.
Effects of perioperative enteral EPA-enriched immunonutrition on meaningful loss of lean body mass after total gastrectomy for gastric cancer: Post hoc analysis of a phase III study.
Authors: Yoshikawa Takaki , Hiki Naoki , Sakamaki Kentaro , Ito Seiji , Fujitani Kazumasa , Takiguchi Nobuhiro , Kawashima Yoshiyuki , Nishikawa Kazuhiro , Sasako Mitsuru , Ida Satoshi , Aoyama Toru , Honda Michitaka , Sato Tsutomu , Nunobe Souya , Ogata Takashi , Cho Haruhiko 
Published: February 2017

85 Background: Total gastrectomy for gastric cancer significantly reduces body weight, especially lean body mass (LBM), through surgical stress and decrease of the calorie intake. Eicosapentaenoic acid (EPA)-enriched enteral nutrition (EPA-EN) could modulate immune function and limits catabolism. In our phase III study to compare perioperative standard diet with or without EPA-EN, additional EPA-EN did not contribute to prevent weight loss or LBM. Recently, 5% or more LBM loss after surgery was reported to impair compliance of post-operative S-1 adjuvant chemotherapy. This post hoc study explored whether additional EPA-EN prevented meaningful loss of LBM for compliance of adjuvant chemotherapy after surgery. Methods: Key entry criteria of this phase III study was (1) histologically proven adenocarcinoma of the stomach, (2) clinical T1-T4a and M0, (3) R0 resection is possible by total gastrectomy, (4) sufficient oral intake, and (5) sufficient organ function. The patients were randomized to Group A: no supplementation with oral nutrients (standard diet) or Group B: standard diet with oral supplementation of ProSure including 600 kcal with 2.2 g EPA for 7 days before surgery and for 21 days after surgery. For both groups, patients underwent total gastrectomy with Roux-en Y reconstruction. Results: A total of 127 patients (Group A: 63, Group B: 64) were enrolled in the study. All background factors were well balanced between the both groups. Median relative performance of supplement in group B was 100% before surgery and 54% after surgery. 5% or more LBM loss at 1 month after surgery was observed in 44 patients (80.0%) in group A and in 37 patients (67.3%) in group B (p = 0.194), while that at 3 months after surgery was found in 51 patients (91.1%) in group A and in 43 patients (76.8%) in group B (p = 0.070). Conclusions: Perioperative standard diet with EPA-enriched enteral nutrition tended to prevent meaningful loss of LBM after total gastrectomy. Further analysis is required whether perioperative EPA enriched EN improve compliance of S-1 adjuvant chemotherapy after total gastrectomy. Clinical trial information: UMIN000006380.
Perioperative chemotherapy in locally advanced gastric cancer in Chile: From evidence to daily practice.
Authors: MÃ¼ller Bettina G. , Garcia Carlos , Sola Jose Antonio , Benavides Carlos , Werner Patrick , Buchholtz Martin , Reyes Cosmelli Felipe , Corvalan Alejandro Hernan 
Published: February 2017

92 Background: Gastric cancer is the leading cause of cancer death in Chile, with mortality rate of 26.7/100.000 in men, placing the country among the highest mortality rates worldwide. For locally advanced gastric cancer, a multimodality treatment is recommended, but in Chile, the treatment covered by the public health insurance, which assists more than 70% of the patients, is surgery alone. We conducted an observational study to assess efficacy and toxicity of perioperative chemotherapy (CT) in public hospitals in Chile (NCT01633203). Methods: Patients with locally advanced, operable gastric carcinoma, defined as presence of invasion of serosa or beyond (cT > 3 AJCC 2002) and/or lymph node metastasis (cN+) without distant metastasis (M0), were offered to receive preoperative CT with Epirubicin+Cisplatin+Capecitabine (ECX) regimen for 3 cycles followed by curative surgery with D2 lymphadenectomy. Staging abdominal CT scan was mandatory, laparoscopy was recommended. Patients with gastric retention, severe dysphagia or contraindications for CT were excluded. All patients signed the IRB approved informed consent form prior to enrolment. Data were collected using the OpenClinica platform. Results: Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23-76 years) and most patients had good performance status at baseline (ECOG 0: 42, ECOG 1: 19). Tumor site was proximal in 24 (39%), medial in 16 (26%) and distal in 10 patients (16%). All but 4 patients (n = 57, 93%) completed three cycles of preoperative CT as planned. Fifty-five patients were operated and 54 (89%) had curative R0 resection. Of these, 36 (67%) had pT0-2, and 15 (28%) had pN0 tumors. A complete pathological response was found in 2 patients. Two patients were not operated for other reasons (one patient refused surgery and one patient presented a cerebrovascular accident during preoperative CT and died), and 5 patients (8%) progressed. As of September 1, 2015, 32 patients died. Three-year survival rate was 49%. Conclusions: Perioperative CT is feasible in public hospitals in Chile and should be offered as an alternative to primary surgery for patients with locally advanced gastric cancer.
Predicting response to neoadjuvant chemoradiotherapy in esophageal cancer by textural features derived from pretreatment FDG-PET scans.
Authors: Beukinga Jorn , Hulshoff Jan-Binne , Sijtsema Marianna , van Dijk Sanne , Muijs Christina , Burgerhof Johannes , Kats-Ugurlu Gursah , Slart Riemer , Slump Kees , Mul Veronique E. , Plukker John Theodorus 
Published: February 2017

93 Background: 18-F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is currently the imaging method of choice in assessing response of neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients. PET/CT derived texture analysis is potentially more useful than common PET/CT measurements in response assessment and might also be of predictive value in different cancer types. The aim of this study was to develop a model to predict response to nCRT in EC based on pretreatment FDG-PET derived textural features in combination with clinical parameters. Methods: We reviewed 80 locally advanced EC patients who underwent pretreatment FDG-PET/CT and radiation planning CT scans between 2009 and 2015. Patients received nCRT according to the CROSS regimen (carboplatin/paclitaxel/41.4Gy) followed by esophagectomy. We analyzed 7 clinical, 16 geometry-based, and 87 different texture features derived from pretreatment FDG-PET images of the radiotherapy gross tumor volume. Ordinal logistic regression analysis was performed to construct a prediction model for treatment response, which was pathologically classified in complete, partial and no response on the Mandard tumor regression grade (1 vs. 2-3 vs. 4-5). The performance of this model was estimated by comparison with clinical outcome. Results: Pathologic examination revealed 16 (20.0%) complete, 46 (57.5%) partial, and 18 (22.5%) non- responders. Response analysis yielded the following independent predictive textural features: SUVmin, small zone low gray level emphasis, and contrast; and the independent predictive clinical parameters: nodal stage, endoscopic tumor length, and gender. The model has a sensitivity/specificity, positive/negative predictive value, and accuracy of 69%/97%, 85%/93%, and 91% for the prediction of complete response and 61%/79%, 46%/88%, and 75% for non-response, respectively. Conclusions: The prediction model constructed in this study, shows a good overall performance level in predicting response to nCRT in EC patients, but requires further external validation and refinement before it can be used for clinical decision making.
Evaluation of preventive factors for postoperative pulmonary complications following esophagectomy for T1bN0M0 cancer using data from JCOG0502.
Authors: Nozaki Isao , Mizusawa Junki , Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Daiko Hiroyuki , Yano Masahiko , Udagawa Harushi , Nakagawa Satoru , Takagi Masakazu , Tsunoda Shigeru , Abe Tetsuya , Nakamura Tetsu , Hihara Jun , Toh Yasushi , Akutsu Yasunori , Shibuya Yuichi , Katayama Hiroshi , Nakamura Kenichi , Kitagawa Yuko 
Published: February 2017

98 Background: Postoperative pulmonary complications (PPCs) are the most common cause of serious morbidity following esophageal cancer resection and are associated with a poorer prognosis in esophagectomized patients (pts). We have recently reported that thoracoscopic esophagectomy (TSE) decreases PPC frequency. However, it remains unclear whether the frequency is further decreased by the combination with laparoscopic esophagectomy (LSE). This study aimed to clarify the combined effect of TSE with LSE on the prevention of PPCs and to determine the preventive factors for PPCs following esophagectomy using data from JCOG0502. Methods: JCOG0502 is a four-arm prospective study comparing esophagectomy with definitive chemoradiotherapy for T1bN0M0 cancer, with randomized and patient preference arms. The primary endpoint is overall survival, which will be analyzed in 2018. PPCs were defined as one or more of the following ≥ grade 2 postoperative morbidities per CTCAE v3.0: pneumonia, atelectasis, and acute respiratory distress syndrome. The use of TSE and/or LSE was decided at the surgeon’s discretion. Results: Totally, 379 pts (11 in the randomized and 368 in the patient preference arm) were enrolled between 2006 and 2013 from 37 institutions. Of the 210 pts who underwent esophagectomy, TSE was performed in 101 pts (TSE with laparotomy in 43 pts and TSE with LSE in 58 pts), while esophagectomy via thoracotomy was performed in 109 pts. PPCs occurred less often in pts who underwent TSE than esophagectomy via thoracotomy (15.8% vs 30.3%, p = 0.01); however, there was no difference in the frequency of PPCs between those who underwent TSE with laparotomy and TSE with LSE (16.3% vs 15.5%). In univariate analysis, both TSE (shown above) and less blood loss ( < 350 mL) were associated with the prevention of PPCs (16.3% vs 30.2%, p = 0.02). Multivariate analysis showed that TSE was associated with the prevention of PPCs [Odds ratio, 0.33; 95% confidence interval (0.12-0.88); p = 0.03]. Conclusions: This study indicated that TSE was the only independent preventive factor for PPCs following esophagectomy, and LSE had limited effectiveness in the prevention of PPCs when it is combined with TSE. Clinical trial information: UMIN000000551.
Phase II study of nivolumab (ONO-4538/BMS-936558) in patients with esophageal cancer: Preliminary report of overall survival.
Authors: Kojima Takashi , Hara Hiroki , Yamaguchi Kensei , Hironaka Shuichi , Iwasa Satoru , Kato Ken , Tsushima Takahiro , Yasui Hirofumi , Ura Takashi , Muro Kei , Satoh Taroh , Doki Yuichiro , Ohtsu Atsushi , Hamamoto Yasuo , Kitagawa Yuko 
Published: February 2017

TPS175 Background: Patients with esophageal cancer refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a human monoclonal IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced esophageal cancer. We conducted phase II, single-arm, multi-center trial in JAPAN (JapicCTI-No.142422).Methods: The target population was esophageal cancer patients aged ≥ 20 years with ECOG performance status of 0 or 1, who had received one or more previous treatments and not pre-selected by PD-L1 status. Nivolumab (3 mg/kg IV Q2W) was administered to patients until observing unacceptable toxicity or disease progression assessed at 6 week intervals. The primary endpoint was the proportion of patients with a confirmed objective response assessed by independent review committee according to RECIST 1.1. Planned sample size was 60 patients (P0 = 5, P1 = 15, α = 0.025 (one-side), 1-β = 0.8). Data cutoff, 17 May 2015.Results:We enrolled 65 patients with esophageal carcinoma: median age 62.0 years (range, 49-80 years); male/female, 54/11; ECOG PS 0/1, 29/36, Histological type was squamous in all pts. The median prior regimens was 3.0 (range, 1-8); 44 patients (67.7%) were treated with prior esophagectomy and 44 patients (67.7%) with prior radiation therapy. There were 64 evaluable patients for efficacy, and 11(17.2%) of 64 patients had objective response (CR/PR, 1/10). 16 (25.0%) of 64 patients had stable disease. The median overall survival was 12.1 months in 64 evaluable patients. The incidence of drug-related Serious AEs was 11 events (9/65 patients): Lung infection(2[3.1%]), Dehydration(2[3.1%]), Interstitial lung disease (2[3.1%]), etc. The patients with grade 3 pneumonitis improved with supportive care. There was no treatment-related death. We will introduce the updated efficacy and safety data of this trial. Conclusions: Nivolumab has meaningful activity and a manageable safety profile in pretreated esophageal cancer. These data support the assessment of nivolumab in randomized, controlled, phase III studies of second-line treatment. Funding: ONO Pharmaceutical CO.,LTD. Bristol-Myers Squibb Clinical trial information: 142422.
Phase II trial of bolus 5-FU/l-LV regimen as salvage line chemotherapy for oral fluorouracil resistant unresectable gastric cancer (HGCSG1502).
Authors: Muranaka Tetsuhito , Yuki Satoshi , Sawada Kentaro , Kawamoto Yasuyuki , Nakatsumi Hiroshi , Dazai Masayoshi , Hayashi Hideyuki , Nakamura Michio , Ishiguro Atsushi , Sogabe Susumu , Kobayashi Yoshimitsu , Miyagishima Takuto , Iwanaga Ichiro , Tateyama Miki , Hatanaka Kazuteru , Kato Takashi , Sakamoto Naoya , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

TPS177 Background: S-1, oral fluorouracil agent compounding tegafur, 5-chloro-2, 4-dihydropyrimidine, and potassium oxonate for gastric cancer showed non-inferiority relative to a continuous infusion of fluorouracil in JCOG9912 trial. Similarly, in ISO-5FU10 trial, S-1 revealed non-inferiority effect compared with the treatment with bolus 5-FU/l-LV treatment. It is known that there is a different mechanism of anti-cancer effect between continuous 5-FU and bolus injection of 5-FU. Continuous infusion of 5-FU and oral fluorouracil inhibit DNA synthesis, however, bolus injection of 5-FU causes dysfunction of RNA in a concentration-dependent manner. So we considered bolus 5-FU/l-LV treatment might be useful for oral fluorouracil resistant patients with gastric cancer. Methods: This is a multi-centered single-arm prospective phase II study in Japanese patients with oral fluorouracil resistant gastric cancer. The key eligibility criteria are as follows: 1) Pathologically diagnosed gastric adenocarcinoma: 2) Unresectable advanced, metastatic, or recurrent disease; 3) resistance of S-1 or capecitabine; 4) resistance or intolerance of cisplatin or oxaliplatin, paclitaxel or docetaxel, and ramucirumab; 5) 20 years of age or older; 6) ECOG PS of 0, 1 or 2. Bolus 5-FU/l-LV regimen consists of l-LV 250mg/m2/2h iv and 5-FU 600mg/m2 iv bolus given intravenously once weekly followed by 2-week rest period, within a 8-week cycle. The primary endpoint is progression free survival rate after 1cycle administration. And the secondary endpoints are response rate, disease control rate, overall survival, progression free survival, time to treatment failure, adverse events, dose intensity and QOL by EORTC QLQ-C30. This study is recruiting in Hokkaido Gastrointestinal Cancer Study Group and registered as UMIN000018882. Clinical trial information: UMIN000018882.
A randomized, double-blind, placebo-controlled phase III study of cisplatin plus a fluoropyrimidine with or without ramucirumab as first-line therapy in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (RAINFALL, NCT02314117).
Authors: Fuchs Charles S. , Tabernero Josep , Al-Batran Salah-Eddin , Chau Ian , Ilson David H. , Van Cutsem Eric , Shitara Kohei , Ferry David , Emig Michael , Vanvoorden Veerle , Hsu Yanzhi , Xu Yihuan , Sashegyi Andreas , Das Mayukh , Shah Manish A. 
Published: February 2017

TPS178 Background: Ramucirumab, a human IgG1 monoclonal antibody directed to the ectodomain of VEGFR-2, prevents ligand binding to the receptor, blocking activation of downstream receptor-mediated pathways. Ramucirumab has demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) in 2 phase III registration studies (REGARD, RAINBOW) in patients in second-line treatment of gastric cancer. This global phase III trial will compare PFS in patients with HER2-negative, metastatic gastric or GEJ adenocarcinoma receiving ramucirumab with cisplatin/capecitabine (or 5-FU) versus placebo with cisplatin/capecitabine (or 5-FU) as first-line treatment. The trial is conducted in 137 sites in the Americas, Europe and Japan and is currently open to enrollment. Methods: Eligible patients will be randomized to receive ramucirumab (8mg/kg on days 1 and 8, based upon population pharmacokinetic modelling) or placebo with cisplatin/capecitabine every 21-day cycle until disease progression, unacceptable toxicity, or other withdrawal criteria are met. The primary endpoint is PFS; OS is the key secondary endpoint. Efficacy will be considered at 3 analysis points: futility analysis for PFS, primary analysis of PFS & final analysis of OS. A gatekeeping strategy will be used to assess PFS and OS. The OS endpoint will only be tested if the PFS test is significant to control Type I error at 5% across both endpoints. An exposure/safety analysis will be done after 60 patients have started the 3rd cycle. The study has 90% power to demonstrate a PFS advantage assuming HR = 0.70 and 80% power to demonstrate an OS advantage assuming HR = 0.77. Other secondary endpoints include PFS2 (the time from randomization to disease progression after the start of additional systemic anticancer treatment, or death from any cause, whichever occurs first), objective response rate, safety and quality of life. As of 9/11/2015, 128 patients have been enrolled in 19 countries. The 1st exposure/safety analysis is underway. Clinical trial information: NCT02314117.
Assessment of laparoscopic stomach preserving surgery with sentinel basin dissection compared with standard gastrectomy with lymphadenectomy in early gastric cancer: A study protocol of a multicenter randomized phase III clinical trial (SENORITA trial).
Authors: Ryu Keun Won , Park Ji Yeon , Kim Young Woo , Nam Byung-Ho , Lee Young Joon , Jeong Sang-Ho , Park Ji-Ho , Hur Hoon , Han Sang Uk , Min Jae-Seok , An Ji Yeong , Hyung Woo Jin , Cho Gyu Seok , Jeong Gui Ae , Jeong Oh , Park Young-Kyu , Jung Mi Ran , Yoon Hong Man , Eom Bang Wool 
Published: February 2017

TPS179 Background: Along with marked increase in early gastric cancer (EGC) in Eastern countries, there has been an effort to adopt sentinel node concept in EGC to reduce immediate postoperative complications and preserve gastric function. Based on the promising results from the previous quality control study prior to phase III trial, this prospective multicenter randomized controlled trial aimed to elucidate the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection (SBD) compared to standard laparoscopic gastrectomy. Methods: This trial is an investigator-initiated, open-label, multicenter randomized controlled phase III trial with non-inferiority design. Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma with a diameter of 3cm or less are eligible for the present study. A total of 580 patients (290 per each group) will be randomized to either laparoscopic stomach-preserving surgery with SBD or standard surgery. The primary end-point is 3-year disease-free survival (DFS) and the secondary endpoints include postoperative morbidity and mortality, quality of life, and 5-year DFS and overall survival. The qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial. Discussion: The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves the similar oncologic outcomes and improved quality of life compared to the standard gastrectomy in EGC patients. Clinical trial information: NCT01804998.