bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical expression of receptor-tyrosine-kinase in patients with gastric cancer: A multicenter study in Japan.
Authors: Kimura Yutaka , Kurokawa Yukinori , Matsuura Nariaki , Fujita Junya , Imamura Hiroshi , Ebisui Chikara , Nushijima Yoichiro , Adachi Shinichi , Nishikawa Kazuhiro , Nishida Toshirou , Takiguchi Shuji , Mori Masaki , Doki Yuichiro 
Published: February 2017

41 Background: Treatment of HER2 positive gastric cancer (GC) with trastuzumab, receptor-tyrosine-kinase (RTK) inhibitor, has led to significant gains in overall survival. Several other targeted therapies are currently undergoing preclinical and clinical testing in some malignancies and GC, directed against diverse oncogenic RTK, therefor it is important to define the expression pattern of target RTK in GC. A multicenter retrospective study was conducted to evaluate the correlation between the expression of some RTKs, HER2, EGFR and c-KIT, and clinicopathological features in GC. Methods: A total of 153 cases with GC which was surgically resected between 2000 and 2006 were registered from nine hospitals. The neoadjuvant treatment cases were excluded. Tumors were centrally examined for HER2, EGFR and c-KIT status with immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) for HER2. The relation between the expressions of HER2, EGFR and c-KIT and clinicopathological factors was examined by Fisher’s exact test. The hazard ratio (HR) for death was estimated, and overall survivals (OS) were compared between positive and negative cases of HER2, EGFR, and c-KIT using log-rank test. Results: The proportion of positive cases with IHC of HER2, EGFR and c-KIT was 7.8%, 14.4% and 11.1%, respectively. There was no significant correlation between the expression of HER2, EGFR and c-KIT and differentiation, location and depth. HER2-positive cases tended to be more frequent in differentiated type tumors. EGFR-positve cases were more frequent in lymph node metastasis (P=0.013). c-KIT-positive cases tended to be more frequent in T1-T2 tumors. OS in HER2-positive cases were clearly worse than in HER2-negative cases (HR 2.23 (95%CI, 1.16-4.38); P=0.014). EGFR-positive cases had a tendency to be worse than in EGFR-negative cases (HR 1.60 (95%CI, 0.94-2.71); P=0.082). c-KIT-negative cases were worse than in c-KIT-positive cases (HR 0.42 (95%CI, 0.17-1.02); P=0.048). Conclusions: This study showed that HER2 expression is a factor of poor prognosis and that EGFR-positive status and c-KIT-negative status tended to be associated with worse outcomes in resected GC.
PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).
Authors: Schwartzberg Lee Steven , Rivera Fernando , Karthaus Meinolf , Fasola Gianpiero , Canon Jean-Luc , Yu Hua , Go William Y. 
Published: February 2017

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]
Bevacizumab (BEV) continued beyond first progression in patients (pts) with metastatic colorectal cancer (mCRC) previously treated with BEV + chemotherapy (CT): Biomarker findings from ML18147.
Authors: Kubicka Stefan , Von Moos Roger , Greil Richard , Sastre Javier , Osterlund Pia J. , Arnold Dirk , André Thierry , Van Cutsem Eric , Mueller Thomas , Reyes-Rivera Irmarie , Bennouna Jaafar ,   on behalf of the ML18147 study investigators
Published: February 2017

452 Background: In ML18147, BEV + standard CT was continued as 2nd-line treatment for pts with mCRC progressing after 1st-line BEV + CT. ML18147 met its primary and secondary endpoints and had a comprehensive biomarker programme, including exploratory analyses of immunohistochemistry (IHC) and single nucleotide polymorphisms (SNPs). Methods: Tumour samples were analysed by IHC for VEGFA, VEGFR1, VEGFR2 and neuropilin-1; H-scores were generated. Tumor angiogenesis was determined by stereological analysis of CD31-stained microvessels; 183 SNPs of 30 mainly angiogenesis-related genes were genotyped. We assessed consistency of treatment effect point estimates, i.e. hazard ratios (HRs) on the same side of 1. Analyses were not adjusted for multiple testing or powered to detect statistically significant treatment by biomarker interactions. Results: IHC data were available for 213 pts (26% of ITT population) and SNP data for 274 pts (33% of ITT). There was no significant evidence of biomarker expression levels or their cellular localisation correlating with BEV treatment effect. Point estimates for a CD31 derivative (i.e. vessel or tumour area) suggested a trend for being predictive for overall survival (OS; HR 1.39 and 0.70 for CD31 derivative <median and ≥median, respectively), similar to data from previous studies. Other previously reported correlations (progression-free survival [PFS] with VEGFA and NRP1 in NO16966; OS with NRP1 in AVAGAST) were not seen. SNP analyses confirmed previous correlations for OS (VEGFA, VEGFR2) and suggested additional biomarker candidates (PFS: VEGFA, VEGFR1, VEGFR2, EGLN3; OS: VEGFR2, EGLN1). Five EPAS1 (HIF2α) SNPs were associated with BEV treatment effect, thus confirming previous findings of HIF2α SNPs as a predictive biomarker for BEV treatment effects. Conclusions: Exploratory IHC and SNP analyses in ML18147 revealed potential biomarker candidates for BEV in pts with mCRC. SNP analyses of angiogenesis-relevant genes were consistent with previous findings for a subset of SNPs, consolidating their role as potential predictive biomarkers of BEV treatment across indications. Clinical trial information: NCT00700102.
The influence of treatment response on the impact of resection margin status after preoperative chemoradiotherapy in rectal cancer.
Authors: Chie Eui Kyu , Lee Jooho , Kim Kyubo , Jeong Seung-Yong , Park Kyu Joo , Park Jae-Gahb , Kang Gyeong Hoon , Han Sae-Won , Oh Do-Youn , Kim Tae-You , Bang Yung-Jue , Ha Sung W. 
Published: February 2017

505 Background: Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated. Methods: Total of 403 patients with locally advanced rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM and/or less than 1 cm for DRM, 158 cases were included as a study cohort. All patients underwent conventionally fractionated radiation with dose over 50 Gy and concurrent chemotherapy with 5-FU or capecitabine. Median follow-up duration was 44.9 months. Results: The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were 83.3%, 75.6%, 86.3%, and 77.4% respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference using maximal chi-square method. In univariate analysis, the shorter CRM was significantly related with worse clinical outcomes, whereas DRM was not. In multivariate analysis, CRM of 1.5mm, ypN, and perineural invasion were prognosticators for OS, DFS, LRFS, and DMFS. CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging. However, poor responders demonstrated a significant difference according to the CRM status. Conclusions: Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was different for treatment response. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study needs to be validated with larger independent cohort. [Table: see text]
Assessment of the impact of systemic chemotherapy (SC) on the quality of life (QOL) in patients with metastatic unresectable appendiceal epithelial neoplasms (AEN).
Authors: Eng Cathy , Choe Jennifer , Overman Michael J. , Fournier Keith F. , Phillips Jonathan , Baum George , Wolff Robert A. , Royal Richard E. , Mansfield Paul F. , Basen-Engquist Karen 
Published: February 2017

522 Background: AEN is a rare malignancy ranging from indolent well-differentiated carcinoma to highly aggressive signet ring carcinoma. Optimal therapy is cytoreductive surgery (CRS) followed by heated intraperitoneal chemotherapy (HIPEC). Yet some patients (pts) are suboptimal for CRS/HIPEC, and are considered for SC. We have previously reported our retrospective analysis suggesting overall survival (OS) benefits from SC. We then opted to assess the impact of SC on QOL in unresectable AEN pts for which no standard of care exists. Methods: 50 pts who initiated SC were prospectively enrolled at our institution between Oct. 2008 and Nov. 2011. EORTC (3.0) QLQ-C30 and QLQ-OV28 surveys were provided at baseline and quarterly for one year. Data were analyzed with Linear Fixed Effects models using SAS Proc Mixed. Baseline and 6 month follow-up scores were tested separately for all QOL outcomes. Subscale means were converted to scaled values from 0 to 100. Positive change over the interval indicated improvement, except in symptom scales where positive change indicated worsening symptomatology. Results: 26 pts (52%) were male, median age was 64 (37-80). All pts received 5-FU-based treatment, and 37 (74%) received a biologic agent. 18 pts (36%) had poorly differentiated histology. Statistically significant change was noted in 2 subscales (Table). Overall, the Global subscale demonstrated no significant change from baseline (MME=2.9095, p=0.4422). Conclusions: In light of the possible OS benefit of systemic treatment in unresectable AEN as previously presented, our data suggest that palliative SC does not decrease QoL and in fact correlates with improved emotional well-being, and diminished symptoms including myalgias, arthragias and weakness. Awareness of these clinical and psychiatric results will better enable clinicians to ensure optimal outcomes for their AEN patients while on treatment.[Table: see text]
Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of adverse events.
Authors: Dazai Masayoshi , Fukushima Hiraku , Sato Yasushi , Yuki Satoshi , Ohnuma Hiroyuki , Okuda Hiroyuki , Tsuji Yasushi , Kawamoto Yasuyuki , Hatanaka Kazuteru , Iwanaga Ichiro , Koike Masahiko , Kato Takashi , Nakamura Michio , Sogabe Susumu , Fujikawa Koshi , Hosokawa Ayumu , Hisai Hiroyuki , Tateyama Miki , Sakata Yuh , Komatsu Yoshito ,   Hokkaido Gastrointestinal Cancer Study Group
Published: February 2017

554 Background: Panitumumab (Pmab) is a fully human monoclonal antibody specific to the epidermal growth factor receptor. It has been associated with very few infusion reactions, but has been pointed out more severe skin toxicity, compared to cetuximab which is a chimeric antibody.To evaluate the safety of Pmab for patients (pts) with metastatic colorectal cancer (mCRC) in daily clinical practice in Japan, retrospectively. Methods: Two hundred pts with mCRC treated by Pmab contained chemotherapy were retrospectively registered from 20 centers in Japan (HGCSG1002 study). Adverse events were evaluated using Common Terminology Criteria for Adverse Events(CTCAE) Version 4.0. Results: Of 195 pts were able to evaluate for adverse events. Patients’ characteristics were as follows; male/female 112/83, median age 64 (range 40-82), ECOG performance status (0/1/2-) 103/71/21. Treatment line (1st/2nd/more than 3rd): 17/26/152. Grade 3 or higher adverse events related to Pmab were hypomagnesemia (11.5%), rash acneiform (14.3%), paronychia (4.6%). Adverse events accounted for 7.3% of pts discontinuation, but there were no treatment-related deaths. Grade 3 or higher hypomagenesaemia and rash acneiform were observed more often in more than 3rd line treatment, compared to 1st or 2nd line treatment (1st or 2nd/3rd-, 1/ 17, p=0.128, 2/26, p= 0.05). Conclusions: Severe hypomagnesemia was observed more often in daily practice in Japan, compared with previous reports. Grade 3 or higher hypomagnesemia and rash acneiform were observed more often in more than 3rd line setting, compared with 1st or 2nd line settings.
Cost-effectiveness of regorafenib for pretreated metastatic colorectal cancer patients in the United States.
Authors: Seal Brian S. , Özer-Stillman Ipek , Whalen John , Ambavane Apoorva , Yaldo Avin , Pawar Vivek 
Published: February 2017

578 Background: There is an unmet need for treatments that provide a survival benefit for patients with heavily pretreated metastatic colorectal cancer (mCRC). In a randomized, double-blind, placebo-controlled trial, patients treated with regorafenib plus best supportive care (BSC) had significant improvement in overall survival (OS) versus patients in the placebo arm receiving BSC alone. The aim of this study was to estimate the cost-effectiveness of regorafenib for the treatment of patients with mCRC after failure or intolerance to irinotecan-, oxaliplatin-, and fluorouracil-based regimens, from the perspective of a U.S. health care payer. Methods: A cohort-partition model was developed to simulate treatment costs and survival for patients treated with regorafenib or BSC alone. Survival was projected by fitting Weibull distributions to trial data. Mean duration of treatment (3.0 months regorafenib, 2.1 months BSC), utilities (0.71 on treatment, 0.59 post-treatment) and serious adverse event rates were also based on trial data. Monthly drug monitoring and physician fee costs were based on Medicare fee schedules. Routine mCRC care and adverse event unit costs were obtained from an analysis of administrative claims in two large managed care databases. Costs were estimated in 2012 USD. Results: Patients treated with regorafenib had prolonged survival versus BSC alone (0.75 versus 0.60 years) and also had higher lifetime costs ($97,700 versus $59,494). The improvement in quality-adjusted life years (0.47 versus 0.37) was small due to the heavily pretreated nature of the patient population. The increase in costs was attributable to increases in costs for drug acquisition, adverse events , and routine care from increased survival. Conclusions: Regorafenib increases life expectancy for patients with pretreated metastatic colorectal cancer. The cost of this benefit could be considered high; however, it could be justifiable given high unmet need for these patients. The increase in cost is primarily due to drug acquisition costs, similar to other recent treatments for metastatic cancers.
The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST.
Authors: Park Seong Joon , Ryu Min-Hee , Ryoo Baek-Yeol , Sohn Byeong Seok , Kim Ki-Hun , Oh Sung Tae , Yu Chang Sik , Yook Jeong Hwan , Kim Byung Sik , Kang Yoon-Koo 
Published: February 2017

62 Background: Several retrospective studies have suggested that surgical resection of residual lesions could be beneficial if resection was done after disease control (partial response or stable disease) with imatinib in patients with metastatic or recurrent GIST. However, the benefit of surgical resection has not been proven yet compared to imatinib alone. Therefore, we compared the outcomes of surgical resection of residual lesions after imatinib (SI group) with those of imatinib alone (IM group) in patients with metastatic or recurrent GIST controlled with imatinib treatment. Methods: A total of 134 patients with metastatic or recurrent GIST who showed at least 6 months of disease stabilization or response to imatinib were included in this retrospective analysis. Patients were categorized into SI (n=42) or IM (n=92) group. To reduce the selection bias, propensity scores and inverse-probability-weighting (IPTW) adjustment were used in the outcome analysis. Results: Patient and tumor characteristics were statistically similar between SI and IM groups, except median age (51 in SI, 58 in IM, p=0.002), and metastases to peritoneum (12 in SI, 56 in IM, p=0.001). The patients in SI group underwent surgery of residual disease after a median 19.1 months of imatinib treatment (range, 7.2-87.0). With a median follow-up of 58.9 months (range, 15.4-129.1), progression-free survival (PFS) and overall survival (OS) were significantly longer in SI group than in IM group (PFS, 87.7 vs 42.8 months, p=0,001; OS, not reached vs 88.8 months, p=0.001). Multivariate analysis revealed SI group as well as female sex, KIT exon 11 mutation, and low initial tumor burden were associated with longer PFS, and SI group and low initial tumor burden were associated with longer OS. Even after applying IPTW adjustment, SI group showed significantly better outcome in terms of PFS (hazard ratio [HR], 2.326; 95% CI, 1.034-5.236; p=0.0412) and OS (HR, 5.464; 95% CI, 1.460-20.408; p=0.0117). Conclusions: This study strongly suggests that surgical resection of the residual lesions after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST.
Randomized phase II study comparing dose-escalated weekly paclitaxel (wPTX) versus standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).
Authors: Takahari Daisuke , Shitara Kohei , Yuki Satoshi , Nakamura Michio , Kondo Chihiro , Tsuda Takashi , Kii Takayuki , Tsuji Yasushi , Utsunomiya Setsuo , Ichikawa Daisuke , Hosokawa Ayumu , Ishiguro Atsushi , Matsuo Keitaro , Oze Isao , Muro Kei 
Published: February 2017

64 Background: wPTX is one of the standard second-line chemotherapies for AGC. Meanwhile, retrospective analysis of neutropenia during wPTX showed better overall survival (OS) among patients with neutropenia compared to patients without neutropenia. Therefore, we conducted randomized phase II trial comparing dose-escalated wPTX with dose adjustments determined by degree of neutropenia versus standard-dose wPTX for patients with previously treated AGC. Methods: Patients with AGC that progressed during 1 or more previous chemotherapy regimens were randomized to a standard dose of weekly paclitaxel (80 mg/m2, standard dose arm) or an escalated dose of weekly paclitaxel (80 mg/m2 on day 1, 100 mg/m2 on day 8, and 120 mg/m2on day 15 unless severe toxicity nor neutropenia<1500 is observed, escalated dose arm). The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and safety Results: From September 2010 to November 2011, a total of 90 patients were randomised. Number of previous line of chemotherapy was 1 in 55% and 2 or more in other 45%. Among the 44 patients of dose escalated arm, the dose of wPTX was escalated to 100 mg/m2 in 41 patients (93.2%) and then to 120 mg/m2in 29 patients (65.9%). Median PFS was significantly longer in dose escalated arm than standard dose (4.3 months. vs. 2.5 months, HR, 0.61; 95% CI, 0.39-0.95; p=0.03). ORR was 30.3% with dose escalation and 17.1% with standard dose (p=0.2). DCR was significantly higher with dose escalation (78.8% vs. 48.6%, p=0.009). Frequency of neutropenia (grade 1-4) was significantly higher with dose escalation (88.7% vs. 60.0%, p=0.002), but no significant difference was observed in grade 3/4 (40.9% vs.31.1%, p=0.34). Grade 3 peripheral sensory neuropathy was relatively common in dose escalated arm (13.6% vs. 6.7%, p=0.27). Conclusions: Dose escalated wPTX was associated with significantly longer PFS and higher DCR in patients with previously treated AGC in comparison with standard dose. The result of OS will be presented at the meeting Clinical trial information: UMIN000004055.
Efficacy analyses of a randomized phase III clinical trial of combined therapy with CPT-11/CDDP versus CPT-11 alone in patients with advanced or recurrent gastric cancer refractory to prior S-1 chemotherapy.
Authors: Inagaki Hitoshi , Nishikawa Kazuhiro , Fujitani Kazumasa , Sugimoto Naotoshi , Shigematsu Tadashi , Ishiguro Tohru , Tsuburaya Akira , Nakamura Masato , Nashimoto Atsushi , Yamane Takao , Yamada Makoto , Imano Motohiro , Iijima Shohei , Oka Yoshio , Kataoka Masato , Hironaka Shuichi , Andoh Hideaki , Morita Satoshi , Sakamoto Junichi , Tsujinaka Toshimasa 
Published: February 2017

69 Background: There has been no established regimen as the second-line treatment for advanced gastric cancer (AGC), though CPT-11 showed survival benefit over BSC. Combination of CPT-11 with CDDP is one of the promising regimens as the second-line chemotherapy after S-1 mono-therapy. Methods: This is a prospective, multicenter randomized phase III study comparing CPT-11+CDDP (Arm A) vs. CPT-11 alone (Arm B) in patients with advanced or recurrent gastric cancer resistant to S-1 mono-therapy or prior adjuvant chemotherapy using S-1. Eligibility criteria include histologically confirmed gastric adenocarcinoma, age over 20 years old, PS: 0-2, adequate organ functions and written informed consent. Arm A: patients received CPT 11 60mg/m2 and CDDP 30mg/m2 on day 1, q2w. Arm B: patients received CPT-11 150mg/m2on day 1, q2w. Stratification was made according to PS, advanced or recurrence cases, institution and presence or absence of measurable target lesions. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), time to treatment failure (TTF), response rate (RR), and safety. Results: 168 patients were registered between 2007 and 2011. Arm A (n=84) and Arm B (n=84) were well balanced for baseline factors. Median age was 67 vs 68 years old, number of advanced/recurrence after resection was 36/48 vs 35/49, and median number of treatment course was 5 vs. 6 (range:0-31, 0-39). Common grade 3/4 toxicities in Arm A vs. Arm B were neutropenia; 35.4% vs. 27.2% (p=0.259), anemia; 15.9% vs. 3.7% (p=0.009), diarrhea; 0% vs. 2.5% (p=0.152), nausea; 3.7% vs. 4.9% (p=0.687), vomiting; 1.2% vs. 3.7% (p=0.305), anorexia 6.1% vs. 8.6% (p=0.534). The rate of patients who were required dose modification for these toxicities was 22.9% vs 21.4%. The pooled OS, PFS and RR for both Arms were as follows; 13.8 months (95% CI, 10.7 to 17.5), 4.5 months (95% CI, 3.7 to 5.1), and 13.7%. Conclusions: There was no significantly difference in the incidence and severity of adverse events in both Arms except for anemia. Updated efficacy data of secondary endpoints will be presented. Clinical trial information: UMIN000002571.