bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective cohort study on the safety and efficacy of cetuximab for metastatic colorectal cancer patients: The HGCSG0901 study—Analysis of cetuximab refractory.
Authors: Yuki Satoshi , Komatsu Yoshito , Kawamoto Yasuyuki , Tsuji Yasushi , Naruse Hirohito , Hosokawa Ayumu , Kusumi Takaya , Ishiguro Atsushi , Saitoh Soh , Sakata Yuh 
Published: February 2017

639 Background: In the NCIC CTG CO.17 trial comparing in the Best Supportive Care (BSC) and cetuximab (Cmab) monotherapy for patients as third line treatment, median survival time (MST) of patients assigned to BSC was 4.8 months in the wild-type KRAS, and 4.6 months in the KRAS mutant.In contrast, MST of patients assigned to Cmab in the same trial was 6.1 months, and median progression-free survival (mPFS) was 1.9 months, so the difference (Survival Beyond Progression: SBP) between MST and mPFS was about four months. From past reports, the prognosis after 3rd line and later Cmab refractory was very poor. We performed survival analysis of after Cmab refractory. Methods: Of 269 cases registered in the multi-institutional retrospective study (HGCSG0901) treated with Cmab, 233 patients for Cmab refractory of 3rd line or after treatment line were analyzed. Overall survival after Cmab refractory for patients for 3rd line or after treatment line were evaluated for association with prognostic factors such as presence of peritoneal dissemination, the number of metastatic organs, Albumin, ALP, CEA, CA19-9 at the time of Cmab refractory, KRAS mutational status, chemotherapy after Cmab refractory using univariate and multivariate Cox proportional hazard model. Results: MST after refractory for patients with Cmab administration after 3rd line treatment was 4.3 months, which was comparable with SBP of previous clinical trials. Results of multivariate analysis suggested that, PS, presence of peritoneal dissemination, the number of metastatic organs, Albumin, ALP at the time of Cmab refractory and chemotherapy (both already refractory drug only and non refractory drug included) after Cmab refractory were independent prognostic factors after Cmab refractory. Conclusions: PS, presence of peritoneal dissemination, the number of metastatic organs, Albumin, ALP at the time of Cmab refractory and chemotherapy after Cmab refractory should be regarded as an important factor for prognosis after Cmab refractory in colorectal cancers.
Bevacizumab activity in gastric cancer cells with high expression of VEGF.
Authors: Lee Hee Yeon , Shin Jung-Young , Kim Jeong-Oh , Zhang Xiang-Hua , Oh Ji-Eun , Kang Jin Hyoung 
Published: February 2017

64 Background: Metastasis of cancer cells is associated with numerous activating molecules, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α. Excess VEGF production induces hematogenous metastasis in gastric cancer (GC) cells. To understand the anti-metastatic effect of bevacizumab, an anti-VEGF monoclonal antibody developed for selective inhibition of tumor angiogenesis, we investigated VEGF-induced expression of key adhesion molecules in human umbilical vein endothelial cells (HUVECs) and the inhibitory effect of bevacizumab on the adhesion of GC cells expressing high levels of VEGF. Methods: We measured the soluble VEGF (sVEGF) produced by 7 GC cells by ELISA. We evaluated intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin expression in HUVECs pretreated with SNU-1-conditioned medium (SNU-1 CM) or recombinant VEGF (rhVEGF) at different time points by western blotting. Results: We identified that SNU-1 cells secreted the highest sVEGF concentration in 7 GC cells. After rhVEGF pretreatment, ICAM-1 and E-selectin expression were highest at 4–6 h and 2 h, respectively, but VCAM-1 expression was unchanged. Bevacizumab cotreatment markedly decreased VCAM-1 and E-selectin expression to basal levels, whereas ICAM-1 expression was unaffected. The SNU-1 adherent cell percentage decreased following bevacizumab cotreatment of SNU-1 CM- or rhVEGF-pretreated HUVECs. Investigation of SNU-1-cell invasiveness through activated HUVECs revealed less than 10 invasive adherent cells, whereas no cells were found after bevacizumab cotreatment. Conclusions: Our preclinical data suggests that bevacizumab, might contribute to anti-metastasis by inhibiting SNU-1 cell adhesion to HUVECs by reducing E-selectin and VCAM-1 expression.
Therapeutic effect of TAS-102 (A) in patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy by the Köhne model (Km).
Authors: Nishina Tomohiro , Yoshino Takayuki , Mizunuma Nobuyuki , Yamazaki Kentaro , Komatsu Yoshito , Baba Hideo , Tsuji Akihito , Yamaguchi Kensei , Muro Kei , Ohtsu Atsushi 
Published: February 2017

650 Background: TAS-102 is a novel oral antitumor agent consisting of trifluorothymidine and thymidine phosphorylase inhibitor. In the TAS-102 phase II study, TAS-102 significantly improved overall survival (OS) compared with placebo (P) in pts with mCRC who had 2 or more prior regimens and refractory to fluoropyrimidine, irinotecan and oxaliplatin (A: 112pts; P: 57 pts; median OS, 9.0 vs 6.6 months (M); HR, 0.56; p = 0.0011) [K. Yamazaki et al. JSMO 2011 Abst 10428, Y. Kuboki et al. ECCO 2011 Abst 6005]. Km [Ann Oncol 2002; 13:308-317] suggested predictive prognosis marker and showed 4 parameters to classify pts with mCRC treated 5-FU-based first line chemotherapy into 3 risk groups (low risk group (L), intermediate risk group (IM) and high risk group (H)). We retrospectively evaluated TAS-102 phase II study by Km. Methods: Classification of pts into each risk group was done as follows: L is ECOG performance status (PS) 0-1, 1 tumor site; IM is (1) PS 0-1, >1 tumor site, ALP <300 IU/L and (2) PS >1, WBC <10×109 /L, 1 tumor site; H is (1) PS 0-1, >1 tumor site, ALP ≥300 IU/L, (2) PS >1, WBC <10×109 /L, >1 tumor site and (3) PS >1, WBC ≥10×109 /L. Progression-free survival (PFS) was assessed by an independent review committee. Results: Pts were classified as L/ IM/ H in 36/ 31/ 102 pts. The median OS for TAS-102 vs Placebo were in L (not reached vs 10.1M; hazard ratio (HR), 0.62), in IM (9.0 vs 4.9 M; HR, 0.44) and in H (7.6 vs 5.6 M; HR, 0.58). This risk stratified analysis by Km demonstrated that HR of OS and PFS was similar in each risk group (Table). Conclusions: The OS and PFS of TAS-102 were superior to that of placebo in all risk groups by Km. Further prospective TAS-102 phase III study is necessary to confirm these results. [Table: see text]
Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer.
Authors: Engels Benedikt , Gevaert Thierry , Everaert Hendrik , Sermeus Alexandra , Storme Guy , Verellen Dirk , De Ridder Mark 
Published: February 2017

653 Background: Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For patients who are not amenable for metastasectomy, we demonstrated in a previous study the feasibility of moderately hypofractionated intensity-modulated and image-guided radiotherapy (RT) by helical tomotherapy. Aiming at higher response rates, we evaluated in this study helical tomotherapy delivering 50 Gy in daily fractions of 5 Gy. Methods: Inoperable CRC patients with ≤ 5 metastases were enrolled. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PERCIST v 1.0. Side effects were scored using the NCI CTC AE v 3.0 scale. Results: We report the results of the first 22 patients. Thirteen patients (59%) received previous chemotherapy for metastatic disease, displaying residual (n=7) or progressive (n=6) metabolic active metastatic disease at time of inclusion. A total of 51 metastases were treated. Most common sites were the lung, liver and lymphnodes. One patient (5%) experienced grade 3 dysphagia; 2 patients (9%) and 1 patient (5%) grade 2 dysphagia and diarrhea, respectively. Twenty patients were evaluated by post-treatment PET-CT. Five and 6 patients achieved a complete and partial metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 11 months, 17 patients (77%) developed progressive disease, of which 3 isolated local progression. Five patients (23%) are in remission in all irradiated areas without evidence of distant recurrence. Interestingly, those 5 patients received previous chemotherapy with residual oligometastatic disease at time of inclusion. Conclusions: Ten fractions of 5 Gy resulted in a promising 55% metabolic response rate with limited toxicity. Helical tomotherapy is an attractive modality in the multidisciplinary approach of oligometastatic CRC, more specifically in the consolidation of residual and inoperable oligometastatic disease in patients previously treated with chemotherapy.
Effect of protons on bone marrow and small-bowel exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer.
Authors: Nichols Romaine Charles , Huh Soon N. , Getman Nataliya , Ho Meng Wei , Li Zuofeng , Awad Ziad , Zaiden Robert Anthony , Mendenhall Nancy Price , Mendenhall William M. , Hoppe Bradford S. 
Published: February 2017

669 Background: Determine the potential role for protons in the preoperative treatment of resectable rectal cancer. Methods: Eight consecutive patients with resectable (T2-T3) rectal cancers underwent 3D conformal photon (3DCRT); intensity-modulated photon (IMRT); and 3D conformal proton (PT) treatment planning. Initial target volumes (PTV1) were contoured using the RTOG anorectal atlas guidelines. Boost target volumes (PTV2) consisted of the gross rectal tumor plus a uniform 2cm expansion. Plans delivered 45Gray (Gy) or Cobalt Gray Equivalent (CGE) to the PTV1 and a 5.4 Gy (CGE) boost to the PTV2. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Standard normal tissue constraints were utilized. Wilcoxon paired t-tests were performed to compare various dosimetric points between the 3 plans for each patient. Results: All plans met all normal-tissue constraints and were isoeffective in terms of PTV coverage. Proton plans offered significantly reduced median normal-tissue exposure over the 3DCRT and IMRT plans with respect to: pelvic bone marrow (PBM) at the V5Gy, V10Gy, V15Gy and V20Gy levels and small bowel (SB) at the V10Gy and V20Gy levels. Proton plans also offered significantly reduced median normal-tissue exposure over the 3DCRT plans with respect to the SB at the V30Gy and V40Gy levels. Conclusions: 1.) By reducing bone marrow exposure, protons may reduce the acute hematologic toxicity of neoadjuvant chemoradiation and increase the likelihood of uninterrupted chemotherapy delivery. Bone marrow sparing may also facilitate the delivery of salvage chemotherapy for patients who go on to develop hematogenous metastasis. 2.) By reducing small bowel exposure, protons may reduce toxicity and possibly facilitate the use of more aggressive concomitant chemotherapy with radiotherapy. [Table: see text]
Relationship of myeloid-derived suppressor cells (MDSC) and immune suppression, nutritional impairment, and inflammatory markers in patients with gastrointestinal cancer.
Authors: Shibata Masahiko , Gonda Kenji , Nakamura Izumi , Ohki Shinji , Sakurai Kenichi , Shimura Tatsuo , Takenoshita Seiichi 
Published: February 2017

675 Background: A suppression of cell mediated immunity and malnutrition are commonly seen in patients with advanced cancer and it has been reported that chronic inflammation plays a key role in induction of these conditions. MDSC: myeloid-derived suppressor cells, found as a new type of immune suppressor cells that is closely related to chronic inflammation, have reported to be present in blood circulation in patients with cancer. MDSC have been reported to suppress immune function through several pathways. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 18 normal healthy volunteers, and 53 patients with gastrointestinal cancer including 5 patients with esophageal, 16 with gastric, 26 with colorectal, 3 with bile duct, 1 with pancreatic and 1 with hepatocellular carcinomas, and these cells were used for the detection of MDSC (CD11b+CD14-CD33+) by flow cytometry. PBMC was also used for the PHA-blastogenesis of lymphocytes which is a marker of cell mediated immunity (stimulation indices: SI). Results: MDSC(%PBMC) of whole patients with gastrointestinal cancer, those with gastric cancer and those with colorectal cancer were higher than those of healthy volunteer (3.76+4.90%, 5.18+1.86%, 4.21+1.43% vs 1.59+1.08%, p<0.05, p<0.05, p<0.10, respectively). MDSC of patients with gastrointestinal cancer were also inversely correlated to the SI (r=−0.271, p<0.05) and to the serum concentrations of total protein (r=−0.490, p<0.005). It also tended to correlate to neutrophil counts (r=0.287, p<0.10) and neutrophil/lymphocyte ratios (NLR, r=0.623, p=0.10), and inversely did to lymphocyte counts (r=−0.251, p<0.10).Thus MDSC was successfully detected in peripheral blood and was significantly higher in patients with gastrointestinal cancer. It was related to the inhibition of cell-mediated immunity, hypoaproteinemia and inflammatory markers such as NLR. Conclusions: MDSC seemed to work in the mechanisms of suppression of immune reaction and malnutrition, typically seen in cancer cachexia, in patients with gastrointestinal cancer and may be important as a marker of advancement of malignant diseases.
Treatment of rectal cancer with synchronous metastasis at diagnosis: 65 consecutive Italian cases of the Bologna Multidisciplinary Rectal Cancer Group.
Authors: Pinto Carmine , Pini Sara , Di Fabio Francesca , Cuicchi Dajana , Iacopino Bruno , Lecce Ferdinando , Ercolani Giorgio , Rojas Llimpe Fabiola Lorena , Giaquinta Stefania , Martoni Andrea 
Published: February 2017

676 Background: Twenty per cent of middle/low rectal cancer pts have synchronous distant metastasis (M1) at diagnosis. At present, the treatment strategy in this pt setting is not well defined. This mono-institutional retrospective analysis evaluates the treatment strategy and clinical outcome of three different pt group. Methods: Between January 2000-July 2011 the Bologna Multidisciplinary Rectal Group of S. Orsola-Malpighi Hospital evaluated 65 pts with rectal cancer M1 disease. Three different groups were defined: rectal cancer with resectable metastatic disease (Group A); rectal cancer with potentially resectable metastatic disease (Group B); and rectal cancer with unresectable metastatic disease (Group C). Treatment strategy in the different groups entailed an individualized approach. Results: The distribution per group was: Group A 11 (17%) pts, Group B 28 (43%), and Group C 26 (40%). The pt characteristics were: M 42 (64.6%), F 23 (35.4%); median age 62 years (35-83); median ECOG PS 0 (0-2); cT3 45(69.2%), cT4 20 (30.8%); cN- 10 (15.4%), cN+ 55 (84.6%); M1 sites: liver 32 (49.2%), lung 8 (12.3%), liver + lung 11 (16.9%), ovary/peritoneal carcinosis/abdominal lymph nodes 7 (10.8%), liver + bone 2 (3.1%), >2 sites 5 (7.7%). Forty-three (66.2%) pts underwent to surgery for primary rectal tumor, and 30 (46.2%) pts for metastasis resection (23 liver, 5 lung, 2 liver + lung). Treatments for different groups are shown (Table). Median OS according to the three different groups was: Group A not reached, Group B 32 months (95% CI 24-40), and Group C 16 months (95% CI 7-26). Patients undergoing metastasis resection have higher median OS than those not resected: 44 months (95%CI 12-76) vs 15 months (95% CI 8-23) (p=0.0006). Conclusions: Treatment strategy in synchronous metastatic rectal cancer must consider the possibility of distant metastasis resection. Long-term survival can be achieved using an integrated approach. [Table: see text]
Update of AMC 0201 study: A randomized phase III trial comparing mitomycin-C plus short-term doxifluridine (Mf) versus mitomycin-C plus long-term doxifluridine plus cisplatin (MFP) after curative resection of advanced gastric cancer (NCT00296335).
Authors: Ryoo Baek-Yeol , Kang Yoon-Koo , Min Young Joo , Zang Dae Young , Kim Gyu Yeol , Yang Dae Hyun , Jang Se Jin , Yook Jeong Hwan , Oh Sung Tae , Kim Byung Sik 
Published: February 2017

76 Background: Despite a continuing debate on the role of adjuvant chemotherapy, several studies have suggested that mitomycin-C (M) plus fluoropyrimidine (f) could improve the outcome of curatively resected advanced gastric cancer (AGC) patients (pts). To improve further the adjuvant Mf chemotherapy, we have prolonged the administration of oral fluoropyrimidine (F) and added cisplatin (P) to Mf (MFP) and performed a phase III randomized trial to determine whether this strategy could improve the 3-year relapse free survival (3yRFS) in curatively resected AGC pts (HR=0.63, α=0.05, β=0.1). Three year follow-up results were reported in 2008 ASCO meeting. Here we report long-term follow-up results for confirmation. Methods: Three to 6 wks after R0 resection, the pts who had postoperative stage II-IV were randomized to receive either Mf or MFP adjuvant chemotherapy. For Mf group, 20 mg/m2 of M was iv injected and 4 wks later, 460-600 mg/m2/day of doxifluridine was administered orally for 3 months. For MFP group, the administration of doxifluridine was extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of cisplatin were added to Mf. Results: Between Feb 2002 and Aug 2006, a total of 871 pts were randomized (435 in Mf, 436 in MFP). Sixteen pts were excluded because of ineligibility (11 in Mf, 5 in MFP). Postoperative stages were II in 51.0%, IIIA in 31.1%, IIIB in 9.4%, and IV in 8.5% of pts. With a median follow up of 6.6 yrs in April 2011, a total of 353 events (relapse or death) have been observed. There was no difference in RFS between the two groups (HR, 1.10; 95% C.I. 0.89 – 1.35; p=0.3918; 5yRFS 61.1% in Mf and 57.9% in MFP). Difference in overall survival (OS) was also insignificant (HR, 1.11; 95% C.I. 0.89 – 1.39; p=0.3349; 5yOS 66.5% in Mf and 65.0% in MFP). Conclusions: Long-term follow-up results of AMC 0201 trial confirmed prolongation of doxifluridine administration and addition of cisplatin to adjuvant chemotherapy with mitomycin-C plus 3 months of doxifluridine did not improve the treatment outcome in curatively resected AGC pts.
ABI-007 in the treatment of unresectable or recurrent gastric cancer refractory to fluoropyrimidine-containing regimen: Updated data from the multicenter phase II study.
Authors: Takiuchi Hiroya , Sasaki Yasutsuna , Nishina Tomohiro , Yasui Hirofumi , Muro Kei , Tsuji Akihito , Koizumi Wasaburo , Toh Yasushi , Hara Takuo , Miyata Yoshinori 
Published: February 2017

90 Background: ABI-007 is a novel Cremophor-free nanoparticle albumin-bound paclitaxel. Cremophor-free formulation allows administration using a shorter infusion schedule (30 minutes) and without the need for premedicaion to prevent solvent-based hypersensitivity reactions.This single arm phase II study evaluated the efficacy and safety of ABI-007 given every three weeks to unresectable or recurrent gastric cancer patients (pts) who had received one prior chemotherapy regimen containing fluoropyrimidine and developed disease progression (PD) or recurrence. Methods: Eligibility include: histologically or cytologically confirmed gastric adenocarcinoma , received one prior regimen containing fluoropyrimidine analogs and developed PD or recurrence, age: 20 - 74, at least one measurable lesion by RECIST(1.0), PS:0-2, adequate organ function and written informed consent. Study duration was until PD or unacceptable toxicity developed. Pts received ABI-007 260 mg/m2, i.v. on day 1 of each 21 day cycle) without premedication. The primary endpoint was overall objective response rate (ORR). Results: From April 2008 to July 2010, total of 56 pts were enrolled, 55 received the study treatment, and 54 pts were evaluable for response. Median age was 64, Male/Female was 43/12, PS:0/1/2 was 33/22/0 and number of sites of metastasis corresponding was 1/2/≥3:19/21/15. ORR was 27.8% (15/54; 95%CI, 16.5-41.6) and DCR (disease control rate:CR+PR+SD) was 59.3% (32/54, 95%CI, 45.0-72.4) for all evaluable patients. One confirmed CR was observed. Median progression–free survival was 2.9 months (95%CI, 2.4-3.6), and median overall survival was 9.0 months (95%CI, 6.6-11.5). The most common grade 3/4 toxicities were neutropenia (49.1%), leucopenia (20.0%), lymphopenia (10.9%); and peripheral sensory neuropathy (23.6%). Conclusions: These data demonstrate that ABI-007 showed promising activity with well-tolerated toxicities for previously treated unresectable or recurrent gastric cancer pts.
Outcomes of multivisceral resection of gastric gastrointestinal stromal tumors.
Authors: Ganai Sabha , Posner Mitchell , Prachand Vivek N. , Alverdy John C. , Choi Eugene A. , Waxman Irving , Patti Marco G. , Roggin Kevin K. 
Published: February 2017

91 Background: Despite the recent introduction of imatinib and laparoendoscopic techniques to the management of gastric gastrointestinal stromal tumors (GISTs), outcomes remain uncertain in the setting of multivisceral involvement. Methods: We conducted a retrospective review of 69 consecutive patients who underwent resection of gastric GISTs from October 2002 through August 2011. Median follow-up was 19 months (interquartile range [IQR] 4-37). Results: Patients were 51% female, with a mean age of 65 ± 13 years and BMI of 30 ± 8 kg/m2. Patients undergoing multivisceral resection (n=13) had a longer interval from diagnosis to surgery (7.4 [IQR 1.9 – 15.0] vs. 1.3 [IQR 0.7-3.5] months, p<0.01), greater use of neoadjuvant imatinib (62% vs. 4%, p<0.001), and greater preoperative tumor size (12 ± 8 vs. 4 ± 3 cm, p<0.001) in comparison to gastric-only resections (n=56). Patients were less likely to be managed laparoscopically (8% vs. 71%, p<0.001), had a longer operative time (286 ± 92 vs. 152 ± 65 min, p<0.001), and were less likely to be R0 (69% vs. 98%, p<0.001). While patients undergoing multivisceral resection were more likely to have a pathological complete response to therapy (23% vs. 0, p<0.01), they were also more likely to have metastatic disease present (31% vs. 0, p<0.01). Hospital length of stay was greater (median 8 [IQR 7-9] vs. 3 [IQR 2-6] days, p<0.001). There were no significant differences in grade or mitotic index between groups, or in the use of adjuvant imatinib (54% vs. 23%). Overall survival was less in patients undergoing multivisceral resection (63% vs. 86% at 3 years, p<0.05), as was disease-free survival (52% vs. 71% at 3 years, p<0.05). Median disease-free survival was 50 and 66 months, respectively (p<0.01). Controlling for tumor size, grade, resection status, and the use of neoadjuvant imatinib, multivisceral resection was an independent predictor of disease-free survival (p<0.05). Conclusions: Multivisceral involvement is associated with tumors of greater size, and despite an increased use of neoadjuvant imatinib, it is associated with poor outcome for patients with gastric GISTs.