bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does panitumumab have a clinical benefit in cetuximab-refractory KRAS wild-type metastatic colorectal cancer?
Authors: Watanabe Toshiyasu , Shinozaki Eiji , Kijima Sho , Ohhara Yoshihito , Kuboki Yasutoshi , Takagi Koichi , Ozaka Masato , Ogura Mariko , Kikuchi Yoshinori , Suenaga Mitsukuni , Chin Keisho , Matsusaka Satoshi , Koike Junichi , Funahashi Kimihiko , Urita Yoshihisa , Mizunuma Nobuyuki , Hatake Kiyohiko , Kaneko Hironori , Sugimoto Motonobu 
Published: February 2017

654 Background: Panitumumab and cetuximab can be used in metastatic colorectal cancer (mCRC) and these drugs are IgG2 fully human and IgG1 chimeric (mouse/human) monoclonal antibody against the epidermal growth hactor receptor (EGFR) respectively. The efficacy of panitumumab as a salvage chemotherapy after cetuximab-based chemotherapy failure is not clarified. Methods: This study aimed to evaluate the panitumumab efficacy to KRAS wild-type mCRC patients who failed cetuximab-based chemotherapy. Response, progression-free survival (PFS) and serum tumor marker level (CEA and CA19-9), were assesed. We studied response by days from last cetuximab-based chemotherapy to panitumumab induction (C-P days). Results: 22 patients (11 men, 11 women, median age 54 years m4 0-78 n) were enrolled. All of thease patients were cetuximab-based chemotherapy refractory KRAS wild-type mCRC. After progression, they received panitumumab monotherapy (6 mg/kg every 2 weeks).The best response was SD 10/22 (45.5%), PD 11/22 (50%) and NE 1/22 (4.5%). Overall median PFS was 90 days (13 to 182). The patients C-P days less than 30 days were 15 patients(5:SD, 10:PD). The patients more than 79 days were 7 patient(5:SD, 1:PD, 1:NE). Serum tumor marker level was decreased more than 50% patients. Conclusions: This study suggested that it might be limited as possibility of clinical benefit with panitumumab administration after cetuximab failure.
Capecitabine monotherapy and the clinical significance of neutrophil-lymphocyte ratio versus platelet-lymphocyte ratio in patients with metastatic colorectal cancer.
Authors: Lee Suee , Kwon Hyuk-Chan , Kim Sung-Hyun , Oh Sung Yong , Lee Ji Hyun , Yoon Hyun-Hwa , Choi Hong Jo , Kim Hyo-Jin 
Published: February 2017

660 Background: Oxaliplatin- and irinotecan-based combination chemotherapy with infusional 5-FU and leucovorin are currently the standard therapies for metastatic colorectal cancer. The objectives of this study were to evaluate the efficacy of capecitabine monotherapy as third line therapy for metastatic colorectal cancer after failure of chemotherapy containing oxaliplatin and irinotecan, and to determine whether the neutrophil-lymphocyte ratio (NLR), or the platelet-lymphocyte ratio (PLR) are significant prognostic marker in metastatic colorectal cancer. Methods: We analyzed 60 patients with metastatic colorectal cancer who received capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. Capecitabine was administered at 1250mg/m2 twice daily for 2 weeks, every 3 weeks. The NLR and PLR were calculated from complete blood counts in baseline laboratory test before the first cycle chemotherapy. Results: The overall response rate was 6.7% and stable disease was 41.7%. The disease control rate was 48.3%. The median progression-free survival (PFS) was 2.8 months (95% CI, 1.5-4.1 months) and the median overall survival (OS) was 9.7 months (95% CI, 7.6-11.7 months). The most frequent adverse event was hand-foot syndrome (all-grade 26.6%; grade3 5%). The response of capecitabine, NLR, and PLR were observed as good prognostic markers of OS in univariate analysis (p<0.001, 0.004, and 0.002, respectively). The response of capecitabine and PLR were independent prognostic marker in multivariate analysis (Hazard ratio 2.757, 95% CI 1.357-5.599, p=0.005 and hazard ratio 2.091, 95% CI 1.231-3.552, p=0.006, respectively). Conclusions: The capecitabine monotherapy showed a moderate disease control and a tolerable toxicity profile as third line treatment for metastatic colorectal cancer. The response of capecitabine and PLR may be simple and useful prognostic index for metastatic colorectal cancer.
Liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer in Japanese patients (KSCC 0802).
Authors: Samura Hironori , Beppu Toru , Emi Yasunori , Kakeji Yoshihiro , Saeki Hiroshi , Oki Eiji , Fujita Fumihiko , Inomata Masahumi , Sawai Terumitsu , Akagi Yoshito , Baba Hideo , Natsugoe Shoji , Ogata Yutaka , Tokunaga Shoji , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer
Published: February 2017

666 Background: There is no data concerning liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer by prospective, multi-center study in Japan. The Kyushu Study group of Clinical Cancer (KSCC) conducted a phase II trial in this setting. Methods: Eligibility criteria included unresectable liver limited metastases from histologically confirmed advanced colorectal cancer, ECOG PS 0-1 and adequate general condition. Patients (pts) received 6 cycles of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2 d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) with bevacizumab (5mg/kg) followed by evaluating the liver resectability. (UMIN000001308) Results: Of the 40 pts enrolled from Sept. 9 2008 to Aug. 10 2010; M/F, 29/11; Median age, 63 years (range 37-74); ECOG PS 0/1, 38/2. The median number of administration cycles was 6 (range, 1–7). Response for CR, PR, SD, PD and NE were 0 (0 %), 12 (30.0 %), 22 (55.0%), 3 (7.5%) and 3 (7.5%), respectively. An overall response rate was 30.0% (95% CI: 16.6 % – 46.5 %). The grade 3-4 adverse events were; leukopenia (10%), neutropenia (32.5%), febrile neutropenia (5%), fatigue (2.5%), appetite loss (2.5%), diarrhea (2.5%), mucositis (2.5%), high AST (2.5%) and ileus (2.5%). The number of cases to intent operation was 17 (42.5%), the liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts (25.0%, 95% CI; 12.7 - 41.2 %). Conclusions: mFOLFOX6 with bevacizumab regimen is safe and effective for unresectable liver limited metastases from colorectal cancer, and might be to lead the high liver resectability.
The PARSC trial, a prospective study for the assessment of recurrence risk in stage II colon cancer (CC) patients using ColoPrint.
Authors: Salazar Ramon , de Waard Jan Willem , Glimelius Bengt , Marshall John , Klaase Joost , Van Der Hoeven Jacobus , Capdevila Jaume , Bibeau Frédéric , Stork-Sloots Lisette , Rosenberg Robert 
Published: February 2017

678 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying CC patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in in-silico datasets and independent patient cohorts of stage II and III patients. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. ColoPrint identified two-third of the stage II patients (209/320) as low risk. The 3-year relapse-free survival was 94% for Low Risk patients and 79% for High Risk patients with a HR of 2.74 (95% CI 1.54 - 4.88; p=0.006). Moreover, the profile stratified patients independent of ASCO clinical risk factors. Methods: A prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II CC patients) using ColoPrint has been initiated. Objectives are: (1) to validate the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage II colon cancer; (2) to compare the risk assessment in stage II patients using the ColoPrint profile vs. a clinical risk assessment based on Investigator’s assessment of risk and ASCO high-risk recommendations; (3) to investigate therapy as a potential confounding factor for ColoPrint results; and (4) to assess the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage III colon cancer. Inclusion criteria: age ≥ 18 years, adenocarcinoma of the colon, stage II and III, no prior neo-adjuvant therapy, no synchronous tumors, fresh tumor sample, and written informed consent. The treatment of the patient is at the discretion of the physician adhering to National Comprehensive Cancer Network (NCCN)-approved regimens or a recognized alternative. Results: The trial started in Sept. 2008 with currently 30 participating sites in 11 countries. Thus far, 288 eligible stage 2 and 251 stage 3 patients have been enrolled. Conclusions: The aim is to enroll 575 stage II patients to differentiate between 3 year RFS predicted by ColoPrint and clinical factors.
Racial differences in the pattern of hematologic toxicity in the treatment of colorectal cancer.
Authors: Oluwole Olalekan O. , Wu William , Wolff Steven N. , Hande Kenneth R. 
Published: February 2017

679 Background: 5-fluorouracil (5-FU), a synthetic fluoropyrimidine, is a critical component of chemotherapy in many cancers. Its metabolites inhibit Thymidylate Synthetase (TS) causing cessation of DNA synthesis and are misincorporated into DNA and RNA causing ineffective DNA repair and faulty mRNA splicing. The rate limiting step in the catabolism of 5-FU is by the Dihydropyrimidine Dehydrogenase enzyme (DPD) which catabolizes over 80% of 5-FU. Patients with near total DPD enzymatic deficiency develop life threatening toxicity after a single administration and those with less severe deficiency will have delayed elimination of 5-FU and slowly accumulate active metabolites leading to toxicities. Methods: We conducted a pilot retrospective cohort study of African American (AA) and Caucasian patients treated for colorectal cancer over a 9 year period, 2000 – 2008, in this IRB approved study. The primary outcome of interest was the rate of development of grade 3 or 4 neutropenia (Absolute Neutrophil Count <1000/uL = grade 3 and <500/uL = grade 4). Descriptive and univariate analysis were done. To test for differences between AA and Caucasians, we computed independent t-test for continuous and Fisher’s exact test for categorical variables. Relative Risk (RR) and p-values were computed. All statistics were done with SPSS v19 software. Results: There were 66 evaluable patients (40 men, 26 women), 40 AA, 24 Caucasians and 2 of other races. Thirty-eight patients (15 Caucasians and 23 AA) received 5-FU containing chemotherapy. The two groups were comparable in baseline characteristics. AA were more likely to develop grade 3-4 hematological toxicity. Nine of 23 AA (39.1%) and one of 15 Caucasians (6.7%) developed grade 3-4 hematological toxicity. RR 8.56, 95% confidence interval 0.95 – 421.06 (p-value of 0.0561) Conclusions: These results suggest that AA were more likely than Caucasians to have severe hematologic toxicity with the use of 5-FU containing chemotherapy. This difference did not meet statistical significance due to small sample size and few numbers of events in the Caucasian arm. A larger prospective study is needed to further evaluate the observed difference.
Long-term survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma.
Authors: Kleinberg Lawrence , Catalano Paul J. , Forastiere Arlene A. , Keller Steven M. , Anne Pramila R. , Benson Al Bowen ,   Eastern Cooperative Oncology Group
Published: February 2017

69 Background: E1201 included operable esophageal adenocarcinoma, staged II-IVa by EUS and accrual ended Oct 2004. The primary endpoint was pathologic complete response (pCR), a surrogate endpoint generally associated with survival which did not meet criteria for further study of either arm. Long term survival results are now available. Stratification included clinical/EUS stage and ECOG performance status (PS). Methods: 81 eligible patients (pts) began treatment. Arm A was cisplatin (C) 30mg/m2 and irinotecan (I) 50 mg/m2 on days (d) 1, 8, 22, 29 of 45 Gy RT/5 weeks. Post-op therapy was C 30 mg/m2 and I 65 mg/m2 d 1, 8 q21 days x 3. Arm B therapy was C 30 mg/m2 and paclitaxel (P) 50 mg/m2 1 hour infusion d 1, 8, 15, 22, 29 with RT. Postoperative therapy was C 75 mg/m2 and P 175 mg/m2 day 1 q21 days x 3. Results: In Arm A, 26/39 have died. Median survival (S) is 35 m (months) and the 5, 6, and 7 year S was 46%, 39%, and 35%. In Arm B, 31/42 pts have died (one pt refused follow-up). Median S in arm B is 21 m. The 5, 6, and 7 year S was 27%, 27%, and 23%. Survival by EUS stage strata: For strata 1 (Stages T2N0M0 or T3N0M0), 14/20 have died. Median S is 37 m and 5 year S is 44%. In stage stratum 2 (Stages T1-3N1M0 or T1-3N0-1M1a), 43/61 have died. Median S is 24 m and 5 year S is 34%. For PS Strata: Patients with PS 0, had median S 35 m and 5 year S of 37% whereas for those with PS 1, the outcomes were 20m and 35%. Survival differences for the treatments and for these strata were not statistically significant. Conclusions: Long term survival is similar for both treatment arms and does not appear superior to results achieved with 5FU based regimens. The prognostic importance of the pretreatment strata was not confirmed. These data, along with the reported pCR (15% arm A; 17% arm B) and toxicity data (> =grade 3 during chemo/RT 68% arm A; 65% arm B), may have importance in aiding in the design and interpretation of ongoing and planned phase II trials adding novel agents or treatment approaches to backbones built on variations of these two regimens.
FLOX regimen (5-FU, folinic acid, oxaliplatin) and FLIRI regimen (5-FU, folinic acid, irinotecan) as first-line treatment in metastatic and locally advanced gastric cancer: A randomized phase II study.
Authors: Glenjen Nils , Hammerling Katrin , Hatlevoll Ingunn , Småland Rune , Weber Hauge Petra , Eide Geir Egil , Sorbye Halfdan , Dahl Olav , Frykholm Gunilla 
Published: February 2017

71 Background: The Norwegian Gastrointestinal Cancer Group (NGICG) conducted a phase II randomized study comparing the efficacy and safety of FLOX and FLIRI as first line treatment in metastatic or locally advanced gastric cancer. At progression or unacceptable drug related toxicity, a crossover to the other treatment arm should be done, if second line chemotherapy was indicated. Methods: 66 patients from 6 treatment centers in Norway were randomized to FLOX (oxaliplatin 85 mg/m2 on day 1, bolus 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2, or FLIRI (irinotecan 180 mg/m2 on day 1, bolus 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2). Both treatments were repeated every second week. The primary endpoint was response rate (RR) and time to progression (TTP). Secondary endpoints were overall survival (OS) and safety data. Results: At the present time data from 63 patients are available for analysis. First-line treatment: FLOX (n = 32) versus (v.) FLIRI (n = 31): Complete response (CR) n = 0 in both arms, partial response (PR) n = 16 v. 9, stable disease (SD) n = 12 v. 13, progressive disease (PD) n = 3 v. 6, not assessable for evaluation n = 1 v. 3 patients. RR was 50 % in the FLOX arm v. 29 % in the FLIRI arm, p = not significant (n.s), Pearson Chi-Square test. Median TTP was 5 months (95 % CI 2.2-7.8) v. 4 months (95 % CI 2.2-5.8), p = n.s, median OS was 11 months (95 % CI 9.2-12.8 ) v. 10 months (95 % CI 5.7-14.3), p = n.s, Log Rank test. Patient characteristics were well balanced. Febrile neutropenia was present among 10 % of the patients in the FLOX arm versus 7 % in the FLIRI arm. Second line treatment: 30 patients received second line treatment with FLOX or FLIRI. Data regarding RR, TTP, OS and safety will be updated in December 2011. Conclusions: The FLOX and FLIRI regimens are well tolerated among patients with locally advanced and metastatic gastric cancer. As first line treatment the FLOX regime had a higher RR of 50% v. 29% for the FLIRI regime, longer TTP; 5 v. 4 months and longer OS 11 v. 10 months, but the difference did not reach statistical significance.
Adjuvant paclitaxel followed by oral fluoropyrimidines for gastric cancer: Safety data of the factorial phase III SAMIT trial.
Authors: Kobayashi Michiya , Tsuburaya Akira , Yoshida Kazuhiro , Yoshino Shigefumi , Miyashita Yumi , Morita Satoshi , Oba Koji , Buyse Marc E. , Macdonald John S. , Sakamoto Junichi 
Published: February 2017

72 Background: Adjuvant chemotherapy with fluoropyrimidine (FP) with or without platinum for gastric cancer (GC) has become standard almost worldwide; however, there has been no comparison among concurrent, sequential, and monotherapy. Paclitaxel (PTX) is one of key drugs in GC widely used as 2nd-line chemotherapy in Japan. Methods: SAMIT is a randomized, multicenter phase III study of FP (S1 or UFT) vs. PTX followed by FP in patients (pts) with gastric adenocarcinoma. Eligibility includes T3/T4, N0-2, M0 except for positive lavage cytology, chemotherapy- and radiotherapy- naive, being able to start chemotherapy 14 and 56 days after D2 gastrectomy. Pts received either UFT 267 mg/m2/day for 4w, q4w x 6 cycles (arm A); S1 80 mg/m2/day for 2w, q3w x 8 cycles (arm B); PTX 80 mg/m2 Day 1, 8 for the first 3w x 1 cycle, Day 1, 8, 15 q4w x 2 cycles, followed by UFT 267 mg/m2/day for 4w, q4w x 3 cycles (arm C); or PTX as in C, followed by S1 80 mg/m2/day for 2w, q3w x 4 cycles (arm D). The FP cycles was prolonged by 24w after ACTS-GC publication in 2007. Primary endpoint is disease-free survival and total number of patients was calculated to be1480 where 90% power for superiority of C+D group vs. A+B. The Independent Data Monitoring Committee undertook a review of the 1417 pts at the 2nd interim analysis in 2011. Results: Arm A (n=353), arm B (n=359), arm C (n=352), arm D (n=353) were well balanced for baseline factors. The compliance with UFT in arm A and S1 in B was 74% and 76% in the first 12 weeks, and 89% and 90% between week 37 and 48; that in arm C and D was 83% and 80% in the second 12 weeks, and 94% and 84% between week 37 and 48. Numbers of grade 3/4 hematological and non-hematological adverse events (AEs) were 3 and 46, 0 and 64, 5 and 35, and 16 and 67 for arm A, B, C, and D, respectively. Anorexia was the most common AE observed in 5.8%, 6.8%, 1.7%, and 5.1% for arm A, B, C, and D, respectively. There were 363/1323 (27%) deaths and 762/1323 (58%) of pts survived disease free. Conclusions: Adjuvant chemotherapy with sequential PTX and FP for GC was safe and the compliance of the FP part could be better than that of FP monotherapy. The final efficacy results will be formally assessed in 2012.
Seventh edition (2010) of gastric adenocarcinoma AJCC staging system: Is there room for improvement?
Authors: Patel Manali I. , Rhoads Kim F , Ma Yifei , Ford James M. , Norton Jeffrey A. , Poultsides George A. 
Published: February 2017

77 Background: The gastric cancer AJCC staging system recently underwent significant modifications of the T and N categories as well as stage groupings. The new system has not been validated on a US population database, but studies on Asian patients have reported no difference in survival between stages IB and IIA, as well as IIB and IIIA. Methods: California Cancer Registry data linked to Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (gastroesophageal junction tumors excluded) who underwent curative-intent surgical resection from 2002 to 2006. AJCC stage was reclassified based on the 7th edition. Disease-specific survival (DSS) probabilities were calculated using the Kaplan-Meier method and compared using the log rank test. Results: Of 4,985 patients identified, 2,262 had complete pathologic data and known cause of death. Median age was 70 years and 60% were males. Median number of examined lymph nodes was 12 and 39% of patients received adjuvant chemotherapy. The 7th edition AJCC system did not distinguish outcome adequately between stages IB and IIA (P = .25), or IIB and IIIA (P = .33, Table ). By merging stage II into one category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system which showed improved discriminatory ability ( Table ). Conclusions: In this first study validating the new 7th edition AJCC staging system for gastric cancer on a US population, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC system that better discriminates between outcomes. [Table: see text]
Prognostic significance of isolated tumor cells in regional lymph nodes in patients with T2-T3 stage gastric cancer.
Authors: Jin Sung-Ho , Cho Soo-Youn , Lee Kyu-Jae , Park Sunhoo , Yu Hang-Jong , Bang Ho-Yoon , Lee Jong-Inn 
Published: February 2017

8 Background: The prognostic impact of isolated tumor cells (ITCs) in regional lymph nodes is unclear. This study was aimed to evaluate the prognostic significance of ITCs in subpopulation with T2-T3 gastric cancer by adopting the standard definition for ITC (≤ 0.2 mm, detected by H&E or IHC) and micrometastsis (≤ 2 mm, detected by H&E or IHC) in 7th AJCC staging. Methods: A total of three hundred eleven patients diagnosed as pT2-3/N0-2/M0 gastric carcinoma after curative surgery at Korea Cancer Center Hospital between January 1996 and December 2000 was retrospectively studied. All tumor and lymph node specimens by H&E received reexaminations, and 5,825 lymph nodes from 191 patients without macrometastasis (> 2.0 mm) were re-evaluated after IHC staining with anti-cytokeratin (AE1/AE3). And N stage was reclassified into pN0(i-), pN0(i+), pN1mi, pN1, and pN2. Survival analyses were performed using Kaplan-Meier method with Log-rank test and Cox regression model. Results: According to original N stage, 5-year overall survival rates were estimated as 80.5% in N0, 79.3% in N1, 68.8% in N2 without statistical difference between N0 and N1 (p=0.790). Whereas according to reclassified pN stage, survival rates were estimated as 92.3% in pN0(i-), 75.5% in pN0(i+), 84.4% in pN1mi, 76.1% in pN1, and 69.0% in pN2, and significant difference was found between pN0(i-) and pN0(i+) (p=0.034). In the multivariate Cox model with backward conditional method, reclassified pN stage was remained as an independent prognostic factor along with age and tumor location while excluding original N stage, and the hazard ratio (95% CI) of pN0(i+) compared to pN0(i-) was 3.60 (1.08-12.00). Conclusions: The result demonstrates that ITCs in regional lymph nodes is a bad prognostic factor, even after adjusting for other prognostic factors. So we suggest that ITCs should be classified separately from the N0 in gastric cancer staging.