bluuebunny/crossref_metadata_2025 huggingface dataset:
The optimal length of the proximal resection margin in patients with proximal gastric adenocarcinoma: A multi-institutional study of the U.S. Gastric Cancer Collaborative.
Authors: Postlewait Lauren McLendon , Squires Malcolm Hart , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Ejaz Aslam , Acher Alexandra W. , Worhunsky David J. , Saunders Neil , Swords Doug S. , Jin Linda X. , Cho Clifford Suhyun , Cardona Kenneth , Staley Charles A. , Maithel Shishir Kumar
Published: February 2017

108

Background: A 5cm margin is advocated for distal gastric cancers. The optimal length of the proximal resection margin (PM) for proximal (GEJ Siewert II and III, cardia, and fundus) gastric adenocarcinoma (GAC) is not established. Methods: Patients who underwent curative intent abdominal-approach resection for proximal GAC from 2000-2012 at 7 academic US institutions were included. Patients with positive distal margins were excluded. PM length was analyzed by 0.5cm increments and was also dichotomized at the mean and median value. Primary endpoints were local recurrence (LR), recurrence-free survival (RFS) and overall survival (OS). Results: Out of 965 patients, 211 had proximal GAC, and 162 had data available on PM length. 151 patients had negative microscopic margins with a mean value of 2.6cm and a median of 1.7cm (range 0.1-15cm). When PM length was sequentially dichotomized and analyzed at 0.5cm increments (0.5-6.5cm), a greater margin distance for each analysis was not associated with LR, RFS, or OS. Similarly, a PM distance greater than the mean or median value was not associated with LR, RFS, or OS. 11 patients had a positive PM (R1), which was associated with higher N-stage (N3: 73% vs 26%; p=0.007) and increased LR (HR6.1; p=0.009). When accounting for other adverse prognostic factors (grade, lymphovascular invasion, tumor size, T-stage, and N-stage), a positive PM was not independently associated with LR. A positive PM was also not associated with decreased RFS or OS. Conclusions: For an abdominal-approach resection of proximal gastric adenocarcinoma, the length of the proximal margin is not associated with local recurrence, recurrence-free survival, or overall survival. A positive microscopic margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing an abdominal-approach resection of proximal gastric adenocarcinoma, a grossly negative proximal margin is sufficient. Efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.
Analysis of esophagogastric cancer patients enrolled in National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored phase I trials.
Authors: Bando Hideaki , Rubinstein Larry , Harris Pamela Jo , Yoshino Takayuki , Doi Toshihiko , Ohtsu Atsushi , Welch Jack , Takebe Naoko
Published: February 2017

12

Background: In phase I trials, an important entry criterion is life expectancy predicted to be more than 90 days, and this is notoriously difficult to predict. The Royal Marsden Hospital (RMH) prognosis score was developed to help project patient outcomes. At present, there have been no systemic analyses of clinical benefits and prognoses for esophagogastric cancer patients who were registered in phase 1 trials. Methods: All non-pediatric phase I oncology trials sponsored by NCI-CTEP, that began between 2001 and 2013 were considered in this review. The RMH score was determined by 3 variables: LDH level, albumin level, and number of metastatic sites of disease. A log-rank test was used to assess the differences of treatment duration and overall survival (OS) between the groups with different RMH scores. Multivariate Cox proportional hazards model was also used to select the covariates related to the prognosis. Results: Of 4,722 patients with solid tumors, 115 (2.4%) patients were eligible for our analysis. Median age was 59 (range: 30-85), and 73% of patients were men. 54 (47%) patients with esophagus cancer and 61 (53%) with stomach cancer were analyzed. 86 (75%) patients had good (0-1) RMH score and 29 (25%) had poor (2-3) RMH score. Although response rates for good and poor RMH patients were not significantly different (8% vs. 3%; 1-side Fisher's exact test p=0.35), clinical benefit rate (complete response +partial response +stable disease) were significantly different (49% vs. 17%; 1-side Fisher's exact test p=0.002). The median treatment duration and OS for good and poor RMH patients were significantly different, respectively (treatment duration: 86 days and 29 days, Log-rank test P=0.016; OS: 332 days and 63 days, Log-rank test P<0.001). In the multivariate analysis that included the RMH score, age (≥60), ECOG PS (≥2) and the RMH score (2-3) were significant predictors of poor survival. Conclusions: The RMH score is a strong tool to predict the prognosis of esophago-gastric cancer patients who will participate in a phase I trial. The median OS of 63 days for patients with poor RMH score suggests that these patients should not be included in phase 1 clinical trials.
Post-hoc analyses of overall survival (OS) and progression-free survival (PFS) in the TRIO-013/LOGiC trial of lapatinib (L) in combination with capecitabine plus oxaliplatin (CapeOx).
Authors: Bang Yung-Jue , Qin Shukui , Chung Hyun-Choel , Xu Jian-Ming , Park Joon Oh , Jeziorski Krzysztof , Shparyk Yaroslav , Hoff Paulo M. , Sobrero Alberto F. , Salman Pamela , Li Jin , Protsenko Svetlana , Buyse Marc E. , Afenjar Karen , Houe Vincent , Garcia Agathe , Huang Yingjie , Armour Alison , Slamon Dennis J. , Hecht J. Randolph
Published: February 2017

133

Background: Results of the primary and secondary endpoints (OS and PFS, respectively) in the primary efficacy population for the randomized, phase III trial (TRIO-013/LOGiC; NCT00680901), conducted in patients with advanced, HER2-positive upper gastrointestinal adenocarcinoma were previously presented (Hecht JR et al, ASCO 2013). Differences in OS were non-significant between the lapatinib (CapeOx + L) and placebo (CapeOx + P) arms. In prespecified analyses, a treatment effect of L was observed in Asian (majority Chinese or South Korean) patients and patients <60 years (y) when comparing OS in the two arms. Methods: Here, we present the results of post-hoc analyses in TRiO-013/LOGiC which assessed OS, PFS and safety by age and by region. Results: In the Asian subgroups, median OS was longer with L compared with P (see Table). In the rest of the world (ROW) subgroups, median OS was longer in patients <60 y but shorter in patients ≥60 y with L compared with P (see Table). Similar findings were observed for PFS in the 4 subgroups (see Table).More adverse events (AEs) were observed in the Asian subgroups; overall, the incidence of AEs (by region) was similar between age subgroups. Conclusions: OS and PFS were improved in Asian patients (both age subgroups) and younger patients in ROW given CapeOx + L, compared with CapeOx + P. The lower OS and PFS observed in older patients in the ROW subgroups may have affected the overall data. Further trials with CapeOx + L in Asian populations are being considered. Clinical trial information: NCT00680901. [Table: see text]
Outcomes after chemoradiation alone for adenocarcinoma of the esophagus and gastroesophageal junction.
Authors: Pham Anthony , Goodman Karyn A. , Ilson David H. , Janjigian Yelena Yuriy , Ku Geoffrey Yuyat , Rizk Nabil P. , Wu Abraham Jing-Ching
Published: February 2017

138

Background: Definitive chemoradiation (CRT) is a standard treatment for esophageal cancer (EC), particularly squamous cell carcinoma (SCC). However, data for nonsurgical treatment of adenocarcinoma (AC) is limited, and response rates to CRT are lower in AC vs. SCC. Therefore, trimodality therapy is often preferred for AC. However, some patients with AC achieve clinical complete response (cCR) after CRT and decline surgery, or are medically inoperable. We therefore reviewed outcomes after CRT alone for esophageal AC. Methods: All patients receiving full-dose (≥ 50 Gy) CRT without surgery for Stage I-III AC of the esophagus or gastroesophageal junction (GEJ) from 2007-2012 at our institution were included. Complete clinical response (cCR) was defined as negative post-CRT biopsy, or SUVmax ≤ 3 on post-CRT PET if no biopsy was obtained. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 105 patients were included. 11 patients (10%) had T1-2N0 disease; the rest had T3+ or N+ disease. Median follow-up was 49 months. 85 patients (81%) received induction chemotherapy prior to CRT. Median OS was 25 months, with 3/5 year OS of 35% and 20% respectively. 67 patients (64%) had cCR, with median OS of 33 months and 3/5 year OS of 48% and 30%, compared to 15 months in incomplete responders (p<0.001). There were no long-term survivors among incomplete responders. 31 (46%) of cCR patients developed local failure, with 3 and 5 year LRFS of 53% and 46%. Median DMFS was 33 months in cCR patients. Of 10 patients who developed isolated local failure, 6 had salvage surgery, 3 had brachytherapy and 1 had laser ablation. Of these, 3 are alive and 2 are free of disease. Conclusions: This is the largest reported series of CRT alone for esophageal AC. In cCR patients, CRT alone is associated with long-term survival comparable to that expected with trimodality therapy. However, local recurrence still occurs in nearly half of patients with cCR. More study is needed to define which patients with cCR will benefit from immediate surgery after CRT, and improvements in therapy are needed to reduce local failure in patients not eligible for surgery.
Prospective multicenter feasibility study of laparoscopic sentinel basin dissection for organ preserving surgery in gastric cancer: Quality control study for phase III trial.
Authors: Ryu Keun Won , Lee Young Joon , Jeong Sang-Ho , Hur Hoon , Han Sang Uk , Min Jae-Seok , Ahn Ji Yeong , Hyung Woo Jin , Cho Gyu Seok , Jeong Gui Ae , Jeong Oh , Park Young-Kyu , Jung Mi Ran , Kim Young Woo , Yoon Hong Man , Eom Bang Wool
Published: February 2017

143

Background: Clinical application of sentinel node biopsy (SNB) in early gastric cancer (EGC) is still controversial even though promising multicenter trial result with minimal false negatives was already reported from Japan. Moreover laparoscopic approach is considered as minimally invasive in addition to organ preserving surgery. Therefore we conducted this study as a prerequisite quality control for phase III trial. Methods: Laparoscopic SBD was performed in patients with preoperative stage T1-2N0 and tumor size less than 4cm in maximal diameter. Intraoperative endoscopic submucosal injection of Technetium 99m-Human Serum Albumin and indocyanine green was done. All removed sentinel basin nodes (SBN) were investigated with intraoperative frozen Hematoxylin Eosin (HE) stain. Postoperative permanent HE stain was done for SBNs and non-SBNs. Strict checklist consisting of essential 7 steps during laparoscopic SBD was made as the quality control study for phase III trial. Ten cases completion of all essential steps in checklist were defined as qualified institution. Results: Seven institutions participated and 112 patients were enrolled in this study. However 4 patients were excluded due to screening failure. SB detection and SBD was performed in 100 of the 108. Lymph node metastases were found in 11 patients at postoperative permanent HE staining and SBD contained metastatic lymph nodes in 11 patients. The detection rate of SB was 92.6% with mean number of SB and SBN was 1.68 and 9.56. Sensitivity and accuracy were 100% in this study. Frozen results of SBN were compatible with permanent reports except one patient who had one SBN with micrometastasis. As the quality control of each institution for phase III trial, 13 to 20 cases were needed based on our strict checklist. Conclusions: Laparoscopic SBD is feasible and improve the sensitivity comparing to the previous study. This study suggests the promising phase III trial of laparoscopic SBD for minimally invasive and organ preserving surgery in EGC after qualifying participating institutions. Clinical trial information: NCT01544413.
The relationship between health utility, quality of life, and symptom scores in Canadian patients with esophageal cancer.
Authors: Doherty Mark , Naik Hiten , Eng Lawson , Patel Devalben , Kong Qin Quinn , Xu Wei , Brown Catherine , Espin-Garcia Osvaldo , Vennettilli Ashlee , Renouf Daniel John , Faluyi Olusola Olusesan , Knox Jennifer J. , Mackay Helen , Wong Rebecca , Howell Doris , Mittmann Nicole , Darling Gail Elizabeth , Cella David , Liu Geoffrey
Published: February 2017

149

Background: Health Utility scores (HUS) are an increasingly important tool in helping to determine the cost-effectiveness of therapies worldwide. The EQ-5D is a validated HUS questionnaire, with reference data in numerous populations. Previously, HUS in esophageal cancer (EC) were based on limited datasets, and the relationship between HUS and either quality of life (QOL, through the validated FACT-E) or esophageal-specific symptoms such as dysphagia, has not been studied. Methods: This cross-sectional survey of EC patients at Princess Margaret Cancer Centre (2012-2014) assessed EQ-5D, FACT-E, a Visual Analog Scale (VAS), patient reported performance status (PRO-ECOG), and dysphagia scoring. EQ-5D scores were converted to HUS using Canadian references. Correlation analyses were performed between HUS and global FACT-E scores, global dysphagia scores, and specific esophageal symptom scores included in FACT-E. Results: Of 198 patients, median age was 67 (range 32-93) years, 76% were male, with localized (LD stage 1, 6%), regional (RD, stage II-IVA, 62%), and metastatic (MD, stage IVB, 27%) disease. Mean + SEM EQ-5D HUS was 0.80+0.01 (all patients), 0.90+0.05 (LD), 0.82+0.01 (RD), and 0.73+0.03 (MD) [p=0.03]. Mean FACT-E total score was 130, mean total FACT-G score was 80, and mean ECS score was 49. There was a strong correlation between FACT-E total scores and EQ-5D HUS (r=0.73, p<0.001), and mild-to-moderate correlation between FACT-E dysphagia questions and HUS (r= 0.28-0.37; p<0.001, each comparison) and between the odynophagia question and HUS (r=0.28, p<0.001). A moderate correlation was observed between a non-FACT-E based global swallow score and HUS (r=0.48, p<0.001). Conclusions: In this large cross-sectional study of EC patients, stage, QOL, and esophageal-specific symptoms were all associated with HUS. Additional results will be presented on the relationship of VAS, PRO-ECOG and specific FACT-E domains, with HUS and changes in questionnaire scores over time, as well as stage-specific EC reference HUS using UK and USA references. This research enhances our understanding of the factors driving EQ5D HUS in EC, thereby validating its potential usefulness in economic analyses.
Effect of clinical stage on survival outcome in patients with pathological stage I gastric cancer.
Authors: Tokunaga Masanori , Makuuchi Rie , Miki Yuichiro , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: February 2017

178

Background: Patients with clinical stage (cStage) II or III gastric cancer are possible candidates for neoadjuvant chemotherapy. In this situation, contamination of pathological stage (pStage) I patients, for whom gastrectomy without adjuvant chemotherapy is a standard treatment of care, is a problem. However, it is unclear whether survival outcome in patients with cStage II-III / pStage I gastric cancer is as good as that of patients with cStage I / pStage I disease. The aim of the present study is to clarify the effect of clinical stage on survival outcome in patients with pStage I gastric cancer. Methods: The present study included 558 patients with pStage I gastric cancer who underwent gastrectomy between 2002 and 2006 at Shizuoka Cancer Center, Japan. Clinicopathological characteristics were investigated, and survival outcome was compared between cStage I and cStage II-III. In addition, we investigated the effect of other clinical factors, including clinically diagnosed tumor depth (cT) and nodal status (cN), on survival outcome. Results: The present retrospective cohort includs 368 male and 190 female patients, with median age of 64 years Five-year survival rate (5ysr) was significantly worse in cStage II-III (84.2%) than in cStage I (95.5%, p=0.003). 5ysr was also worse in cT2-4 (86.6%) than in cT1 (96.3%, p<0.001). On the contrary, clinical nodal status did not affect survival outcome of pStage I patients. Conclusions: cT and cStage affected survival outcomes of patients with pStage I gastric cancer. Patients who are preoperatively diagnosed with advanced disease have worse survival outcomes and can be candidates for neoadjuvant chemotherapy.
Prognostic factors for PFS in patients with advanced gastric cancer: Using the data from JCOG9912 study.
Authors: Takahari Daisuke , Boku Narikazu , Mizusawa Junki , Nakamura Kenichi , Yamada Yasuhide , Yoshino Takayuki , Yamazaki Kentaro , Koizumi Wasaburo , Fukase Kazutoshi , Yamaguchi Kensei , Goto Masahiro , Nishina Tomohiro , Tamura Takao , Tsuji Akihito , Ohtsu Atsushi
Published: February 2017

180

Background: In advanced gastric cancer (AGC), there are many reports about prognostic factors for overall survival (OS), and we have proposed a prognostic index using four prognostic factors (PS, number of metastatic sites, prior gastrectomy and ALP; Oncologist 2014) based on a phase III trial JCOG 9912 for the first-line treatment (Lancet Oncol. 2009). However, there is no report about prognostic factors for progression free survival (PFS). In this ancillary study, we explored whether prognostic factors are similar or not between OS and PFS. Methods: The subjects of this study were selected from the JCOG9912 which intended to confirm the superiority of irinotecan plus cisplatin (IP) and the non-inferiority of S-1 to5-FU for patients with AGC. Of all enrolled patients in JCOG9912, those who had target lesions and whose complete data were available were analyzed with multivariate analysis using Cox proportional hazard model. Results: 492 out of the 703 pts of JCOG9912 were analyzed, who received either 5-FU (n=163), IP (n=164) or S-1(n=165). The median PFS was 3.7 months for all the subjects, and 2.2 months for 5-FU, 4.9 months for IP and 3.8 months for S-1. Multivariate analysis in all 492 analyzed patients demonstrated seven independent prognostic factors for PFS (Table). Prognostic factors in each treatment were; sex (HR 1.66, 95%CI 1.11-2.49), PS (1.51, 1.04-2.18), Ca (0.39, 0.17-0.86), GPT (2.46, 1.30-4.66) and LDH (1.67, 1.16-2.48) in 5-FU, sex (1.77, 1.10-2.86) in IP, and Na (2.00, 1.01-3.99) and creatinine clearance (0.37, 0.15-0.93) in S-1. Conclusions: There were no common prognostic factors among the three treatment regimens. Prognostic factors for PFS may be different by treatment regimen, although further investigations with larger sample size are needed. [Table: see text]
Do all patients with HER2-positive gastric/GEJ cancer benefit from trastuzumab?
Authors: Yi Jun Ho , Kang Jung Hun , Hwang In Gyu , Ahn Hee Kyung , Lee Soonil , Lim Do Hyoung , Won Young-Woong , Ji Jun Ho , Kim Hyo Song , Rha Sun Young , Oh Sung Yong , Lee Kyung Eun , Lim Taekyu , Kim Seung Tae , Lee Jeeyun , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Park Se Hoon
Published: February 2017

185

Background: Trastuzumab-based chemotherapy became the standard option for patients with HER2 (+) metastatic gastric cancer after ToGA study. However, the OS benefit was not found in Asian and diffuse-type cancer patients. The aim of the current study is to analyze whether Asian ethnicity or poorly differentiated histology (PDH) affects the clinical outcomes of patients who were treated with trastuzumab-based chemotherapy. Methods: We collected the medical records of the patients with HER2 (+) (IHC3+ or IHC2+&FISH+) gastric/GEJ cancer who were treated with trastuzumab-based chemotherapy. The ORR, PFS, and OS were compared according to the patients’ clinicopathologic features and data from ToGA trial. Results: From March 2012 to June 2014, data of 163 Asian patients from 11 institutes in South Korea were collected. The median age was 60 (range 27-85) and the male:female ratio was 116 (71.2%):47 (28.8%). 157 (96.3%) had stomach cancer and 6 (3.7%) had GEJ cancer. Fourteen (8.6%), 62 (38.0%), 71 (43.6%) and 11 (6.7%) patients had well, moderately, poorly differentiated tubular adenocarcinoma (TAC) and signet ring cell carcinoma (SRC), respectively. The ORR was 52.7% (86/163) which is similar to that of the ToGA trial. (47%) The median PFS was 9.8 months (95% CI 8.6 – 11.0 and the median OS was 18.5 months. (95% CI 16.5 – 20.5) These numerical data are slightly better than those of the ToGA trial. (PFS, 6.7 months; OS, 16.0 months) Next, we investigated if PDH (poorly differentiated TAC + SRC) affected on clinical outcomes. The ORR (50.0% vs. 56.6%, p = 0.408) and the PFS (8.8 months vs. 11.2 months, p = 0.109) were slightly inferior in PDH patients but still, they were better than that of the ToGA trial. The median OS was significantly shorter for PDH patients (14.1 months vs. 19.0 months, p = 0.046). Conclusions: While subset analysis of ToGA trial has demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asian ethnicity and poorly differentiated histology, our real world data suggested that even in Asian and patients with PDH, trastuzumab-based chemotherapy is associated with improved clinical outcomes in patients with HER2 (+) gastric cancer.
Comparison of radical surgery followed by adjuvant chemotherapy with radical surgery following neoadjuvant chemotherapy as initial treatment for patients with locally advanced thoracic esophageal squamous cell carcinoma.
Authors: Tsubosa Yasuhiro , Niihara Masahiro , Matsuda Satoru , Ogi Katsuhisa , Takebayashi Katsushi , Kawamorita Keisuke , Onozawa Yusuke , Yokota Tomoya , Tsushima Takahiro , Yasui Hirofumi , Mori Keita , Sato Hiroshi
Published: February 2017

187

Background: Although radical surgery with neoadjuvant chemotherapy (NAC) is a standard therapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) in response to the result of JCOG 9907 study in Japan, there was no significant difference in survival rate at adjuvant chemotherapy and neoadjuvant chemotherapy in cStage III at subanalysis. Methods: Consecutive patients histologically diagnosed with ESCC and planned to undergo radical surgery followed by adjuvant chemotherapy (ADJ) from September 2002 to April 2007 and radical surgery following NAC from May 2007 to December 2011 as initial treatment were eligible for this retrospective study. To select patients who could tolerate transthoracic esophagectomy, respiratory function, Eastern Cooperative Oncology Group performance status, and preoperative complications were considered. As adjuvant and neoadjuvant chemotherapy, cisplatin and 5-fluorouracil were administered every 3 weeks for 2 cycles (FP). Patient characteristics, 3-year overall survival (3yOS) and non complete resection rate were investigated. We analyzed in intent-to-treat analysis. Results: Ninety patients were included in ADJ group, 98 included in NAC group. No significant differences were observed in clinicopathological factors between ADJ group (cStage IB/II/III/IV=6/22/57/5) and NAC group (cStage IB/II/III/IV=10/28/52/8). In intention-to-treat analysis, there was no significant difference in 3yOS rate by ADJ group and NAC group (ADJ group, 67.2%; NAC group, 66.0%; p = 0.301). However, non complete resection rate was significantly higher for NAC group than for ADJ group {ADJ group, 16.7% (3/90); NAC group, 3.4% (14/98); p = 0.009}. In cStage III, non complete resection rate of ADJ group was 3.5% (2/57) and NAC group was 25% (13/52). In the patients with cStage III, NAC group had a tendency for 3yOS rate to be low rather than ADJ group (ADJ group, 66.3%; NAC group, 51.1%; p = 0.09). Conclusions: In cStage III advanced ESCC, FP as NAC may be insufficient and development of the more powerful NAC is desired.
Gastric epithelial dysplasia: Characteristics and long-term follow-up results after endoscopic resection according to morphological categorization.
Authors: Lee Bong Eun , Kim Gwang Ha , Baek Dong Hoon
Published: February 2017

190

Background: Gastric epithelial dysplasia (GED) can be morphologically categorized into adenomatous and foveolar types. To date, there have been few studies on the clinical characteristics of GEDs according to the morphologic types. Therefore, we here aimed to elucidate the clinicopathologic characteristics of patients with GED and the long-term follow-up results after endoscopic resection according to the morphologic characteristics of GEDs. Methods: A total of 357 patients who underwent endoscopic resection for GEDs at Pusan National University Hospital between January 2008 and December 2009 were included in the study. Results: Patients with GED were divided into 3 groups: adenomatous (n = 167, 46.8%), foveolar (n = 103, 28.9%), and hybrid (n = 87, 24.3%) types. Compared to the adenomatous type, foveolar type lesions were more frequently located in the antrum/pylorus, flat/depressed lesions, and normal/reddish in color; and showed more frequent high-grade dysplasia. During the follow–up period (median, 37.3 months), the overall incidence of synchronous and metachronous lesions was 20.8% and 20.1%, respectively; of these, the incidence of synchronous and metachronous gastric cancer was 8.7% and 5.4%, respectively. There were no significant differences in the incidence of synchronous and metachronous lesions according to morphologic types. Conclusions: GEDs appear to have different clinicopathologic characteristics according to morphologic types. Irrespective of the morphology, synchronous and metachronous gastric cancers are commonly found after endoscopic resection of GEDs. Therefore, close follow-up surveillance after endoscopic resection of GEDs should be performed for all patients.
A systematic review of post first-line treatments for advanced gastrointestinal stromal tumor (GIST): Direct pairwise meta-analyses and indirect comparisons.
Authors: Shah Keya , Chan Kelvin K. , Ko Yoo-Joung
Published: February 2017

195

Background: Treatment for metatastatic or unresectable GIST is with imatinib. The majority of patients eventually acquire imatinib resistance, prompting the development of a growing number of agents as post-first-line treatment. Currently no studies directly compare these treatments. Methods: A systematic review was performed through MEDLINE, EMBASE, CENTRAL, and ASCO meeting abstracts up to July 2014 to identify randomized controlled trials that included GIST patients who were previously treated with a first-line chemotherapy for advanced disease. Progression-free survival (PFS) and overall survival (OS) with 95% credible regions were extracted using the Parmar method. Direct pairwise meta-analyses and indirect comparisons using the Bucher method were performed. Results: Four studies were identified for the systematic review. 1 study (n=312) showed that sunitinib in the second-line setting (vs. placebo) improved PFS but not OS. 3 studies (n=528) examined the third-line setting (imatinib resumption vs. placebo; regorafenib vs. placebo; nilotinib vs. best supportive care with or without imatinib or sunitinib). Of the 3 third-line studies, there was significant heterogeneity between placebo-controlled trials and the non-placebo controlled trial (I2= 98%). Direct pairwise meta-analysis using random-effects of the 2 placebo-controlled studies showed that the PFS hazard ratio (HR) was 0.63 (0.22-0.61, p=0.0001), whereas the PFS HR for the non-placebo controlled study was 0.90 (0.65-1.26, p=0.56). These 2 HRs are different statistically (interaction: p=0.002). Indirect comparisons of imatinib resumption vs. regorafenib suggested that the PFS HR was 0.59 (0.31-1.11, p=0.10), trending in favor of regorafenib. OS HRs were not significant for direct or indirect comparison in the third-line setting. Conclusions: The number and size of completed phase III studies and the lack of a standard comparator arm limit the use of direct and indirect comparison methods to determine the best therapeutic option for patients who have progressed on imatinib. At this time, clinicians should interpret the available evidence at an individual level.
Impact of S-1 plus cisplatin neoadjuvant chemotherapy in scirrhous gastric cancer.
Authors: Kunisaki Chikara , Makino Hirochika , Kimura Jun , Takagawa Ryo , Kanazawa Amane , Oshima Takashi , Ota Mitsuyoshi , Kosaka Takashi , Ono Hidetaka , Akiyama Hirotoshi , Endo Itaru
Published: February 2017

198

Background: This study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy. Methods: Two cycles of a 3 week regime of the fluoropyrimidine, S-1 (40 mg/m2, orally, twice daily), with cisplatin (60 mg/m2, intravenously, day 8) were administered to patients, separated by a 2 week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n=27). We compared overall survival and prognostic factors in these patients with a non-neoadjuvant group (n=19). Results: For all patients, univariate analysis identified non-curative gastrectomy and positive lavage cytology as adverse prognostic factors; extended lymph node dissection was a positive prognostic factor. Multivariate analysis showed that non-curative resections independently influenced prognosis (hazard ratio=2.902, p=0.011). In the SP group, positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after SP chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor. Conclusions: After SP neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.
Association of complete pathologic response after neoadjuvant chemoradiotherapy and esophagectomy with overall survival that is independent of the timing of the surgery.
Authors: Singla Smit , Kukar Moshim , Alnaji Raed , Du William , Attwood Kristopher , Hochwald Steven N.
Published: February 2017

200

Background: Esophagectomy after neoadjuvant chemoradiation (nCRT) is known to improve survival outcomes, however the timing of esophagectomy is not well defined. We sought to determine if delayed esophagectomy after nCRT would result in increased likelihood of complete pathological response (cPR) and improve outcomes. Methods: A single institution analysis of all patients treated with nCRT followed by esophagectomy between 2004 and 2014. Patients were divided into four groups based on the timing of surgery (<50 days & >50 days) and pathological response (complete and incomplete), and the data was analyzed for association with survival outcomes Results: Amongst 227 patients (M: 211, F: 16; median age, 61 years) included in our study, the most common site of tumor origin was distal esophagus (n=210, 92.5%), and the most common histologic subtype was adenocarcinoma (n=205, 90.7%). Barretts esophagus was seen in 119 (52.7%), while signet cells were identified in 52 patients (22.9%) on pathology. Most patients had performance status of ECOG 0 or 1 (n=213, 93.8%), and majority of esophagectomies were performed using an open technique (n=157, 69.2%). Most esophagectomies (77.1% vs 22.9%) were performed >50 days after completion of nCRT. These patients had higher proportional incidence of anastomotic leak (11.4% vs 5.8%, p=0.302), conduit necrosis (3% vs 0%, p=0.591), need for reoperation (16% vs 9.6%, p=0.369), and pulmonary (29.7% vs 21.2%, p=0.290) and cardiac complications (18.9% vs 13.5%, p=0.415), but these increases were not significant. There was no significant difference in overall survival (OS) between the groups (median, 48.9 vs 42.6 months in <50 days and >50 days, respectively; p=0.726); however when evaluated by PR, patients with tumors with a cPR were found to have better OS compared to non-cPR (NR vs 33 months, p<0.001). When survival outcomes were compared between the timing of surgery and PR, the difference was not significant (p=0.211). Conclusions: Patients with cPR after nCRT and esophagectomy have improved overall and progression free survival, however, this is independent of the timing of the surgery.
Content analysis of postings in a stomach cancer survivor and caregiver support group on Facebook.
Authors: Hillard James Randolph
Published: February 2017

223

Background: Patients diagnosed with cancer are increasingly turning to patient created social media groups to connect with others suffering from similar conditions. These groups allow sharing of information and support between their members, without involving medical or mental health professionals. This study examines the content of communications within one of these groups in order to identify the needs these groups are addressing, and in order to explore implications for mental health. Methods: This study focuses on a single Facebook group for stomach cancer patients and caregivers which has grown from 239 members a year ago to 1,128 members now and which has been operating for about four years. Two thirds of members are cancer patients, and the rest are caregivers. About 75% of members are from the US. The age range is 40-79, with a mean of 54. Members are 55% women, and 80% are middle class. Most members have been in the group for six to twelve months. The site averages about five original posts and about 50 responses a day. 100 consecutive posts were assigned to one of 12 pre-selected content categories. Results: Primary purpose of each of 100 consecutive posts (1) Sharing updates on their condition: 14 (2) Questions about treatment side effects: 13 (3) General requests for information: 13 (4) Requests for support or prayers: 11 (5) Sharing good news: 11 (6) Welcoming new members: 11 (7) Giving general support: 9 (8) Announcing a death: 5 (9) Sharing information about new treatments: 5 (10) Sharing humor: 4 (11) Sharing bad news: 2 (12) Asking "How are you?": 2. Conclusions: This Facebook group served many of the same functions that are served by face to face support groups for cancer patients. Members routinely shared intimate details with each other, and they routinely asked questions about their illness that they could not get answers to anywhere else. Leaderless Facebook groups such as this one are an important, and little studied, psychological resource for patients suffering from cancer.
Molecular profiling of neuroendocrine tumors (NETs): The Fox Chase Cancer Center (FCCC) experience.
Authors: Vijayvergia Namrata , Boland Patrick McKay , Cohen Steven J. , Gustafson Karen S. , Cooper Harry S. , Astsaturov Igor A. , Engstrom Paul F.
Published: February 2017

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Background: The rarity of NETs can limit clinical trial accrual to develop new therapies. Given fewer approved treatments, a better understanding of underlying biology is critical to development of and assignment of patients (pts) to clinical trials. Methods: Pts with NETs (excluding small/large cell lung cancer) of all grades at FCCC were enrolled onto a prospective IRB approved protocol that utilized an NGS platform to detect somatic mutations (SM) in 50 cancer-related genes (Cancer Code) on archived tissue from primary or metastatic sites. Genes tested included ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO,SRC, STK11, TP53 and VHL. Review of pathology specimens for grade and Ki -67 was also performed. Results: Thirty-nine pts (median age 59 y, males 46%) were enrolled from October 2013 to July 2014. Gene profiling results are available on thirty-five pts. Ki-67 score was reviewed for 31/35 tumors. 6 (20%) pts had high grade (HG) tumors (Ki-67 > 20%) and 25 (80%) had low/intermediate grade (LIG) tumors (Ki-67 ≤20%). Thirteen (37%) pts were found to have SMs and 22 (63%) did not, with 4 (12%) pts’ tumors having >1 SMs (2 HG and 2 LIG tumors). Incidence of SM was 41% (12/29) in Caucasians, 16% (1/6) in other races, 46% (6/13) in smokers and 30% (6/20) in non-smokers. Incidence of SM was 24% (6/25) in LIG NETs and 84% (5/6) in the HG NETs. Among HG tumors, 66% (4/6) harbored TP53 gene mutation and 33% (2/6) were BRAF mutation positive. Conclusions: Tumor-specific mutations are seen in a minority of low grade NETs but are common in high grade tumors. Interestingly, no mutations were identified in pts with unknown primary. Analysis of clinical outcomes based on treatment received is ongoing to assess for possible prognostic/therapeutic implications of these mutations. [Table: see text]
Curative-intent surgery for pancreatic tumors: A review of 3,386 procedures from the Brazilian National Health System.
Authors: dos Santos Lucas Vieira , Lima Joao Paulo , Pontes Luciola De Barros , de Oliveira Cleyton Zanardo , Lopes Gilberto
Published: February 2017

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Background: In Brazil, a large country with major socioeconomic and health access disparities, resource limitations make the management of pancreatic tumors challenging. We aimed to evaluate curative-intent surgical procedures for pancreatic cancer (PC) in the public health care system. Methods: Based on Brazilian’s public health system database (DATASUS) and demographic database (IBGE), we collected data for curative-intent surgical procedures for pancreatic tumors. Information about number of procedures, costs, length of stay, number of perioperative deaths and PC deaths were analyzed for each State and Region and then correlated to State specific population, gross domestic product (GDP) per capita and number of procedures. Results: Between 2008 and 2012, 37,142 patients died due to PC in Brazil, with an increase of 6.3% in mortality annually. Mortality (per 100,000 persons-year) increases from North to South States. GPD per capita (rho=0.636, 2-tailed p<0.001) was associated to PC mortality. Between January 2008 and July 2014, 3,386 procedures were performed, the majority (51.2%) in the Southeast region (particularly in São Paulo State, 32.7%). Total cost was US$ 9,741,315.28, average cost per admission was US$ 2,876.94. The number of procedures per 100,000 residents was higher in Southeast and South Brazil. On multivariate analysis, average cost in each State was only correlated to the number of procedures (β=0.568, p=0.029). The mean length of hospital stay was 16.9 days, with no major differences across regions. The mean length of hospital stay was correlated to GDP per capita and number of procedures. However, no independent association was found on multivariate analysis. A total of 493 patients died, translating into an inpatient mortality rate of 14.55%, higher than observed in high-income countries. The Northern States have the highest mortality rates (mean 25%, and 33% for the State with highest mortality). Neither characteristic was associated to perioperative mortality. Conclusions: This is the first study to evaluate regional disparities in PC care and mortality in Brazil. These disparities calls for regionalized policies aiming the improvement of PC care.
The anatomic location of pancreatic cancer as a prognostic factor for inpatient complications.
Authors: Zhang Shuang Yin , Zhang Shuang Qin , Jiang Jimmy Jing , El-Rayes Bassel F.
Published: February 2017

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Background: Patients with cancer in the head of the pancreas (HP) have a higher frequency of biliary stents, which are associated with complications requiring hospitalization. We hypothesized that hospitalized patients with cancers of the HP have a higher incidence of morbidity and mortality as compared to patients with cancer in the body (B) or tail (T). The primary aim of this study was to investigate whether anatomic location of pancreatic primary lesions is associated with complications and mortality in hospitalized patients. Methods: The Nationwide Inpatient Sample (NIS) database was queried to identify all non-surgical hospital admissions for patients with a diagnosis of pancreatic cancer (PC) for 2011. Based on ICD-9 diagnosis codes, patients were divided into three groups: H, B, and T. Patient demographics, comorbidities, medical complications, and hospitalization outcomes were compared among these 3 groups by univariate analysis. Two sample independent t-tests were used to compare all linear variables, and Chi-squared tests were used to compare categorical data. Results: In total, 4,910 patient admissions were analyzed, of which 3,590 had H, 519 B, and 801 T. No difference was observed in the mean age for all three cohorts (67-68 years). Length of hospitalization for each cohort averaged 6 days. Patient with pancreatic cancer of tail had statistically significant higher incidence of pneumonia (H 4.7%, B 6.2%, T 9.1%, p<0.001), deep venous thrombosis (H 5.5%, B 10.6%, T 13.5%, p<0.001), pulmonary embolic (H 3.3%, B 6.9%, T 9.4%, p<0.001), cerebral vascular events (H 0.7%, B 1.5%, T 2.9%, p< 0.001), ileus (H 6.0%, B 8.1%, T 10%, p<0.001), encephalopathy (H 2.0%, B 1.7%, T 3.5%, p=0.02), acute renal failure (H 13%, B 9.1%, T 15%, p= 0.005), and in-hospital mortality (H 5.3%, B 6.9%, T 8.9%, p<0.001). Conclusions: In this study, pancreatic cancer of the tail correlates with higher incidences of in-hospital complications and mortality. This suggest that the impact of biliary stents on outcome of hospitalized patients with PC may be limited. Anatomic location of pancreatic malignancy may also be utilized as prognostic factor in management of inpatient PC patients.
Prognostic model for survival in patients with advanced pancreatic cancer receiving palliative chemotherapy.
Authors: Uneno Yu , Kou Tadayuki , Kanai Masashi , Yamamoto Michio , Xue Peng , Mori Yukiko , Kudo Yasushi , Kurita Akira , Uza Norimitsu , Kodama Yuzo , Asada Masanori , Masui Toshihiko , Yazumi Shujiro , Matsumoto Shigemi , Takaori Kyoichi , Morita Satoshi , Muto Manabu , Chiba Tsutomu
Published: February 2017

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Background: The prognosis of patients with advanced pancreatic cancer (APC) is extremely poor. Several clinical and laboratory factors have been known to be associated with prognosis of APC patients. However, there are few clinically available prognostic models predicting survival in APC patients receiving palliative chemotherapy. Methods: To construct a prognostic model to predict survival in APC patients receiving palliative chemotherapy, we analyzed the clinical data from 306 consecutive patients with pathologically confirmed APC who received palliative chemotherapy. We selected six independent prognostic factors which remained independent prognostic factors after multivariate analysis. Thereafter, we rounded the regression coefficient (β) for each independent prognostic factor derived from the Cox regression equation (HR = eβ) and developed a prognostic index (PI). Results: Developed prognostic index (PI) was as follows: PI = 2 (if performance status score 2–3) + 1 (if metastatic disease) + 1 (if initially unresectable disease) + 1 (if carcinoembryonic antigen level ≥5.0 ng/ml) + 1 (if carbohydrate antigen 19-9 level ≥1000 U/ml) + 2 (if neutrophil–lymphocyte ratio ≥5). The patients were classified into three prognostic groups: favorable (PI 0–1, n = 73), intermediate (PI 2–3, n = 145), and poor prognosis (PI 4–8, n = 88). The median overall survival for each prognostic group was 16.5, 12.3 and 6.2 months, respectively, and the 1-year survival rates were 67.3%, 51.3%, and 19.1%, respectively (P < 0.01). The c index of the model was 0.658. This model was well calibrated to predict 1-year survival, in which overestimation (2.4% and 0.2% in the favorable and poor prognosis groups, respectively) and underestimation (3.6% in the intermediate prognosis group) were observed. Conclusions: This prognostic model based on readily available clinical factors would help clinicians in estimating the overall survival in APC patients receiving palliative chemotherapy.
Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites.
Authors: Gumusay Ozge , Benekli Mustafa , Ekinci Ozgur , Baykara Meltem , Ozet Ahmet , Coskun Ugur , Uner Aytug , Dursun Ayse , Atak Ecine Yesim , Buyukberber Suleyman
Published: February 2017

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Background: Determination of HER2 status in advanced gastric cancer (GC) is important in clinical decision making. In the ToGA trial, trastuzumab based therapy demonstrated a significant OS benefit in patients with HER2 positive advanced GC. HER2 discordance in GC primary and its metastases has been long debated. The aim of the study was to evaluate the rate of HER2 discordance and its effect on treatment decisions in advanced GC. Methods: A total of 74 patients with advanced GC were included in the study. Both immunohistochemical staining (IHC) and dual-color silver in situ hybridization (SISH) were performed in all patients to evaluate the HER2 status of the primary lesion and paired metastasis. Results: The assessment of HER2 status with the IHC staining method and SISH revealed a discordance rate of 9.5% and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a HER2 negative status in primary tumor (IHC=0, SISH=negative), the HER2 status was positive for liver metastasis (IHC=2+, SISH=positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of HER2 discordance between primary gastric tumor and metastatic lesions compared to the rates reported in previous studies. Detection of a HER2 positive metastasis with a HER2 negative primary tumor suggests that investigation of HER2 is also required for the metastatic lesion and that trastuzumab could be administered in case of a positive result.