bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).
Authors: Shimada Mitsuo , Nishina Tomohiro , Higashijima Jun , Moriwaki Toshikazu , Masuishi Toshiki , Sakai Yoshinori , Ozeki Mitsuharu , Negoro Yuji , Indou Shunju , Denda Tadamichi , Sato Mikio , Morimoto Masamitsu , Nakajima Go , Mizuta Minoru , Takahashi Ikuo , Hiroshima Yoshinori , Ishida Hiroyasu , Maeba Takashi , Hyodo Ichinosuke ,   Shikoku Gastrointestinal Oncology Study Group (SGOSG) and Tsukuba Cancer Clinical Trial Group (TCTG)
Published: February 2017

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.
Response rates to hepatic arterial infusion (HAI) pump therapy in patients with metastatic colorectal cancer liver metastases (mCRC LM) after progression on all standard chemotherapies.
Authors: Cercek Andrea , Aguilo Ariel , Gluskin Jill , Chou Joanne F. , Reidy Diane Lauren , Saltz Leonard , Siegel Cara , Capanu Marinela , Jarnagin William R. , DeMatteo Ronald P. , Allen Peter J. , Kingham Peter T. , Fong Yuman , D'Angelica Michael Ian , Kemeny Nancy E. 
Published: February 2017

597 Background: To evaluate the overall response rate of HAI with floxuridine (FUDR) in the refractory setting in patients with mCRC LM. Methods: After obtaining an IRB waiver a computerized search was performed for patients with mCRC treated with 5FU, oxaliplatin and irinotecan +/- EGFR and VEGF inhibitor from 2003-2012. Charts were reviewed to ensure patients (pts) had received all standard therapies prior to HAI pump placement. All pts received HAI FUDR and no new systemic targeted or cytotoxic therapies were used with HAI pump. Imaging was re-reviewed for confirmation of progression prior to HAI pump placement and for best response using RECIST 1.1 criteria. Results: 75 pts were identified; of these 23 had radiographic disease progression on all standard chemotherapies (5FU, irinotecan and oxaliplatin) prior to having a pump placed. Of the 23 evaluable pts, the median age was 53 (range 37-75). Six pts had low volume extrahepatic metastases at the time of pump placement. The overall response rate (ORR) was 8/23 (35%); 10/23 (43%) pts had stable disease (SD). The median duration of SD was 4 months (range 1-10). Median follow up, measured from the date of HAI initiation, was 24 months and median overall survival (OS) was 22 months (95% CI 13-16). The median hepatic progression free survival (hPFS) was 4.5 months [CI: 3.8-6.7]. Thirteen pts developed extrahepatic disease progression (including 5 pts with preexisting extrahepatic disease). The median overall PFS was 3.9 months [95% CI 2.24-5.33]. Median number of HAI treatments was 4 cycles (range 1-13). Six out of 23 (26%) pts required a 50-75% dose reduction by the second cycle due to elevated liver function tests and 18/23 (78%) required a dose reduction after the 3rd cycle. No pts required stents or developed long term liver or biliary toxicity. Conclusions: In a cohort of 23 patients with mCRC LM, refractory to all standard agents, treatment with HAI FUDR resulted in an ORR by RECIST 1.1 of 35% and median OS of 22 months. Further studies focusing on locoregional therapy in patients with liver predominant disease are warranted. Studies to molecularly characterize these tumors are ongoing.
Mesothelin expression in patients as a novel target in gastric cancer.
Authors: Kelly Ronan Joseph , Pastan Ira , Cowan Morgan L , Montgomery Elizabeth , Hassan Raffit , Alewine Christine Campo , Xiang Laiman , Illei Peter B. 
Published: February 2017

61 Background: Novel targets and therapeutics are of profound importance if we are to improve outcomes in gastric cancer. This study assessed the incidence of mesothelin expression in tumors of Western patients with gastric cancer. In addition, gastric cancer cell lines were then tested for their sensitivity to SS1(dsFv)PE38 (SS1P), a mesothelin-targeted immunotoxin. Methods: Tissue specimens from 127 patients with gastric or gastro-esophageal junction (GEJ) tumors were examined by immuno-histochemistry (IHC) for intensity of staining for mesothelin. Expression of HER2-neu, e-cadherin and c-Met were also assessed. Tumors were considered positive for mesothelin if moderate cytoplasmic/membranous or luminal staining was present in at least 10% of the cells. Gastric cancer cell lines were assessed for surface mesothelin expression by flow cytometry and the viability of cells treated with SS1P was measured. Results: Gastric and GEJ cancers were mesothelin positive in 64/127 tumors (50%) while only 9 tumors (7%) were Her2-neu IHC +3 positive and 8 tumors (6%) were c-Met positive (c-Met low 5% and c-Met high 1%). Mesothelin expression rates changed from stage I tumors to stage IV tumors (39% to 56% respectively). We found that both the AGS and MKN28 gastric cancer cell lines express mesothelin and are sensitive to the immunotoxin with EC50 values in the low picomolar range (0.4 and 0.3 ng/mL, respectively). Conclusions: Mesothelin is a cell surface glycoprotein that is expressed in 50% of resected gastric cancers. Gastric cancer cell lines were exquisitely sensitive to SS1P. The high expression of mesothelin and its sensitivity to the immunotoxin SS1P makes it an attractive tumor associated antigen for therapeutic targeting. Based on these observations clinical trials involving novel mesothelin targeted drugs in gastric cancer are currently in development.
The degree of segmental aneuploidy measured by total copy number abnormalities to predict survival and recurrence in superficial gastroesophageal adenocarcinoma.
Authors: Davison Jon M. , Krill-Burger J. Michael , Yee Melissa K. , Foxwell Tyler J. , Lyons-Weiler Maureen A. , Luketich James D. , Nason Katie S. , Michalopoulos George K. , LaFramboise William A 
Published: February 2017

62 Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. SNP arrays offer the opportunity to evaluate segmental aneuploidy at high resolution throughout the genome. Methods: We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. Results: Recurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6 , KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p=0.032, log rank test) and time to first recurrence (p=0.010, log rank test) compared to those with intermediate CNA counts. In multivariate Cox analysis, there was a 3.4-fold (95% CI, 1.1–10.4) increased hazard of death among cases with intermediate CNA counts after adjusting for other predictors of survival (N stage, angiolymphatic invasion and tumor size). Similarly, there was a 7.3-fold (95% CI, 1.5-34) increased risk of recurrence for these patients. Conclusions: SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count).The non-monotonic association of segmental aneuploidy with survival has been described in other tumors such as breast and ovarian carcinoma. The degree of segmental aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC.
Acceptance of sphincter-preserving surgery for T3 lower rectal cancer after short-course radiotherapy with delayed surgery.
Authors: Beppu Naohito , Yanagi Hidenori , Yamanaka Naoki , Doi Hiroshi , Kamikonya Norihiko , Noda Masafumi , Tomita Naohiro 
Published: February 2017

620 Background: One of the reasons for avoiding sphincter-preserving surgery for lower rectal cancer is difficulty in obtaining a sufficient distal margin. Short-course radiotherapy (SRT) with immediate surgery is not expected to reduce tumor volume, and currently available evidence suggests that it does not increase the sphincter-preservation rate. However, SRT with delayed surgery has been linked to downsizing of the primary tumor during the waiting period. We evaluated the feasibility of sphincter-preserving surgery for T3 lower rectal cancer after SRT with delayed surgery and examined whether a distal margin of ≤ 5 mm has an impact on oncologic outcomes. Methods: We retrospectively studied 161 consecutive patients with lower rectal cancer located below the peritoneum reflection who underwent radical surgery with total mesorectum resection (TME) 3 to 4 weeks after the completion of SRT. The median follow-up was 53.5 months. Results: Sphincter-preserving surgery was performed in 149 (92.5%) of the 161 patients. The procedures were as follows: double-stapling technique, 58 patients; intersphincteric resection, 91; abdominoperineal resection, 10; and Hartmann operation, 2. Among the patients who underwent sphincter-preserving surgery, the distal margin was ≤ 5 mm in 41 patients and > 5 mm in 108. The local recurrence rate was respectively 5.8% vs. 10.4% (p = 0.606), the recurrence-free survival 83.4% vs. 82.8% (p = 0.682), and the overall survival at 5 years 82.3% vs. 87.6% (p = 0.418). Our results suggested that there is no difference in long-term outcomes between a distal margin of ≤ 5 mm and > 5 mm. Conclusions: Sphincter-preserving surgery was performed in 92.5% of patients with T3 lower rectal cancer who received SRT with delayed surgery. Our results confirmed the long-term oncologic feasibility of sphincter-preserving surgery with a distal margin of ≤ 5 mm; there was no negative impact on long-term outcomes such as local recurrence, recurrence-free survival, and overall survival.
Exploratory randomized trial to evaluate the effect of indisetron tablets for preventing chemotherapy-induced nausea and vomiting (CINV)/acute-onset diarrhea induced by IRIS/FOLFIRI: HGCSG0704.
Authors: Kato Sosuke , Fukushima Hiraku , Kato Kanji , Yuki Satoshi , Harada Kazuaki , Kobayashi Yoshimitsu , Sasaki Takahide , Ehira Nobuyuki , Iwanaga Ichiro , Uebayashi Minoru , Dazai Masayoshi , Sogabe Susumu , Miyagishima Takuto , Kudo Mineo , Hatanaka Kazuteru , Naruse Hirohito , Tateyama Miki , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

624 Background: Indisetron is a 5-HT3 receptor antagonist that also antagonizes 5-HT4receptors. Indisetron tablets showed the non-inferiority to ondansetron tablets in terms of efficacy for preventing CINV. Moreover, preclinical data administered with irinotecan showed indisetron significantly reduced stool frequency in mice and inhibited the colonic peristalsis in dogs. We designed a pilot study compared with granisetron in the efficacy and tolerability of indisetron for irinotecan-induced nausea, vomiting and especially in diarrhea. Methods: Advanced colorectal cancer patients treated with FOLFIRI or IRIS (Irinotecan + S-1) with or without bevacizumab were enrolled in this study. Treatment: Arm A: indisetron tablets 8mg po day1. Arm B: granisetron 3mg iv day 1. The primary endpoints were the incidence of acute-onset diarrhea and complete protection from vomiting. Secondary endpoints were tolerability, complete protection from nausea and rate of no rescue medication. Results: Between May 2008 and July 2012, 33 patients (pts) were randomized. The study was closed prematurely due to poor accrual. Arm A: 16 pts, arm B 17 pts. Median age A: 68 y.o., B: 66 y.o.: ECOG PS 0/1: A: 12/4, B: 14/3pts. There was no significant difference of the incidence of acute-onset diarrhea between both groups (18.8% in A vs. 35.3% in B, p = 0.438). The proportion of complete protection from vomiting was 87.5% in A and 88.2% in B (p = 1.000). Similarly, complete protection from nausea, rate of no rescue medication, proportion of patients with a complete response (defined as no emetic episodes and no rescue medication) did not have a significant difference. Severity of nausea/vomiting and AE induced by 5-HT3 receptor antagonist were also similar between two groups. Conclusions: Compared with granisetron, indisetron showed effective and feasible results for preventing CINV induced by FOLFIRI or IRIS. Indisetron had also not improved the incidence of acute-onset diarrhea induced by irinotecan. Clinical trial information: UMIN000010162.
Comparison of two bidirectional hyperthermic intraperitoneal chemotherapy (HIPEC) regimens in patients with colorectal peritoneal metastasis.
Authors: Glockzin Gabriel , Gerken Michael , Lang Sven A. , Schlitt Hans J. , Piso Pompiliu 
Published: February 2017

628 Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) became part of many national and international treatment guidelines as an additive therapeutic option for selected patients with colorectal peritoneal metastasis. Multiple HIPEC regimens are used regarding cytotoxic agents, concentration, perfusion time an other parameters and consistent data for standardization is missing. Methods: 32 consecutive patients after complete macroscopic cytoreduction (CC-0/1) and bidirectional HIPEC for colorectal peritoneal metastasis were retrospectively analyzed. Twenty patients received oxaliplatin-based and twelve patients received irinotecan-based HIPEC. Morbidity and toxicity according to CTCAE v4, mortality and 3-year survival rates hava been determined. Results: The overall 3/4 morbidity rate was 34.4 % and the perioperative mortality rate 0 % in both groups (p = 1.000). Median survival was 26.8 months (95 % CI 15.7-33.1 months) in the IRI group and has not yet been reached in the OX group. 3-year survival rates were 65.0 % in the OX group vs. 41.7 % in the IRI group (p = 0.295). Conclusions: Both HIPEC regimens showed comparable morbidity and toxicity. Nevertheless, oxaliplatin-based HIPEC might be preferred due to the not significant positive survival trend. Prospective randomized trials are needed to compare the different HIPEC regimens and to determine the most effective therapeutic approach.
Clinical benefits of bevacizumab in metastatic colorectal cancer depending on KRAS status.
Authors: Kurimoto Keisuke , Ishigure Kiyoshi , Kato Yoshiyasu , Asai Yasuyuki , Tanaka Nobutake , Ryo Song , Matsushita Hidenobu , Tobinaga Junichi , Fukuyama Ryuichi , Kuroda Hiruhumi , Fujii Tomoo 
Published: February 2017

636 Background: KRAS status is the therapeutic marker of anti-EGFR drug, and may be the prognostic marker of metastatic colorectal cancer (mCRC). However, there is no consensus whether bevacizumab (anti-VEGF drug) benefits patients with mutated KRAS in mCRC. We investigated the clinical benefits of bevacizumab treatment in mCRC depending on KRAS status, retrospectively. Methods: We investigated 49 patients who received chemotherapies with bevacizumab as first-line treatment for mCRC from May 2008 through June 2013. We evaluated response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tumor reduction rate and the adverse events (CTCAE v4.0 - JCOG) depending on KRAS status. Results: The median age of the patients was 66 years (range; 36 - 80). Forty-five patients received oxaliplatin-based chemotherapies with bevacizumab and four patients received irinotecan-based chemotherapies with bevacizumab. KRAS status of 30 patients was wild type and that of 19 patients was mutation type. There was no difference in patient characteristics between KRAS wild type (WT) and mutation type (MT). In all 49 patients, RR was 62.5%. DCR was 91.7%. The median PFS was 10.9 months. In RR, patients with KRAS wild type tumors had better outcome than patients with mutant type tumors (WT : MT, 69.0% : 52.6%, no statistically difference). A similar tendency was seen in DCR (WT : MT, 96.6% : 84.2%, no statistically difference). The average reduction rate in KRAS WT was 42.7% and in KRAS MT was 32.3% (p = 0.309). In the KRAS wild patients, the median PFS was longer than that in the KRAS mutant patients (WT : MT, 11.8 : 8.9 months, Log Rank p = 0.583), but there is no statistically difference between two groups. In median OS, there was no difference between two groups (WT : MT, 21.0 : 20.8 months, Log Rank p = 0.393). The incidence of severe adverse events was not statistically different between KRAS WT group and MT group. Conclusions: Regardless of KRAS status, bevacizumab provides clinical benefits for patients with mCRC.
The efficacy of oxaliplatin-based adjuvant chemotherapy for stage IV colorectal cancer after R0 resection.
Authors: Nakayama Izuma , Suenaga Mitsukuni , Wakatsuki Takeru , Ogura Mariko , Ozaka Masato , Shinozaki Eiji , Matsusaka Satoshi , Chin Keisho , Mizunuma Nobuyuki , Yamaguchi Toshiharu 
Published: February 2017

638 Background: In previous phase III studies (MOSAIC and XELOXA trial), oxaliplatin based chemotherapy was shown to be a standard adjuvant treatment for stage III colorectal cancer (CRC). However, its efficacy for curatively resected stage IV CRC has not yet been clarified. In this retrospective study, we evaluate the efficacy of oxaliplatin based chemotherapy in adjuvant setting for curatively resected stage IV CRC. Methods: Eighty-three patients received adjuvant chemotherapy after R0 resection for Stage IV CRC in our institute between Mar 2007 and Feb 2013. Progression-free survival (PFS), overall survival (OS), completion rate of the treatment and safety were evaluated. Median follow-up time was 33.3 months. Results: Baseline characteristics were as follows (N=83): median age, 61; male/female, 46/37; ECOG PS0, all; colon/rectum, 54/29; synchronous/asynchronous, 41/42. Metastatic sites were liver in 46, lung in 11, peritoneum in 13, lymph node in 12 patients. Median PFS and OS were not reached. Three-year PFS and OS were 67.8% and 88.2%, respectively. Completion rate was 78.6% of the patients. In univariate analysis, completion of treatment, synchronous development and metastasis limited to lung were associated with better PFS, though not statistically significant. Confirmed regional lymph node metastasis of primary tumor showed a trend toward to concern with poor OS. Differences in metastatic site were not observed in both PFS and OS. Multivariate analysis revealed none as a significant prognostic factor. Conclusions: Compared the results to previous trial for stage III CRC, oxaliplatin based adjuvant chemotherapy for stage IV CRC after R0 resection was demonstrated to be consistent in tolerability and efficacy.
Value of mismatch repair deficiency for predicting complete pathologic response to preoperative chemoradiation in rectal carcinoma.
Authors: Aguiar Samuel , Taglietti Paula Mendonca , Begnami Maria D. , Mello Celso Abdon , Santos Erika Maria Monteiro , Lopes Ademar 
Published: February 2017

639 Background: The objective of this study is to investigate the value of mismatch repair deficiency (MMR) in rectal cancers as a predictive fator of response to chemoradiation in rectal cancer. Methods: We evaluated a consecutive cohort of 109 patients with locally advanced rectal carcinomas, treated with a total dose of 5,040 cGy of preoperative radiation therapy, concomitant with infusional 5-FU-based chemotherapy. Radical surgery (TME) was performed in all patients. MMR status was determined by imunohistochemistry in tumor tissue from biopsies prior to chemoradiation. The primary endpoint was complete pathologic response (pCR). Results: 63 patients (57.8%) were male, and the mean age was 60 years (range from 28 to 93). The rate of pCR was 18.3%. Among clinical variables (age, sex, distance to dentate line, per-treatment CEA level, and clinical assessment of response), only clinical complete response (cCR) was significant associated with cPR (p=0.009). Only two patients (1.8%) presented tumors with MMR deficiency. These 2 patients had cPR. Despite the very low rate of MMR deficiency, the association with cPR was significant (p=0.032). Conclusions: Considering the low rate of MMR deficiency found, we do not consider MMR status as a good tool for predicting pathologic response to chemoradiation in rectal cancer. Further investigation can be considered among the subgroup of Lynch syndrome patients.