bluuebunny/crossref_metadata_2025_split huggingface dataset:
ISO-CC-005: A phase I/II study of Modufolin (MTHF) in combination with 5-FU, irinotecan, and oxaliplatin ± bevacizumab in patients with metastasizing colorectal cancer.
Authors: Taflin Helena Anna , Ganlov Karin M E , Guren Tormod Kyrre , Papadimitrou Christos , Kentepozidis Nikolaos K. , Haux Johan , Pfeiffer Per , Carlsson Goran Ulf 
Published: January 2019

838 Background: Chemotherapy treatment of Colorectal Cancer, often include 5-Fluorouracil (5- FU). 5-FU inhibits the enzyme thymidylate synthase (TS), stopping the supply of thymidine for DNA synthesis. 5-FU is always combined with a folate, which enhances the 5-FU effect. Marketed folates such as LV/L-LV are prodrugs needing enzymatic conversion. Modufolin is the natural, biologically active form of the folates and is expected to be efficacious in a larger proportion of patients with less inter- and intra-individual variability Methods: ISO-CC-005 is a multi-center, phase I/II study in mCRC patients eligible for 5-FU/folate therapy alone or in combination with irinotecan or oxaliplatin ± bevacizumab. The study investigates safety and tolerability of Modufolin at 4 dose levels by analysing the number and severity of AEs, SAEs and DLTs. Efficacy is evaluated as ORR after four cycles of chemotherapy. Gene expression, deoxyuridine levels as an indirect marker of TS inhibition and time to death is also investigated. Three to six patients per cohort are included. All receives Modufolin twice every two weeks during at least four cycles of chemotherapy. Results: Today, 42 patients have been enrolled and 40 have initiated treatment. 13 are 1st line patients, 16 are in 2nd line, 10 are in 3rd line and 1 is in 5th treatment line. 19 SAEs have been reported in 12 patients, 3 of these were judged as at least possibly related to Modufolin. No SAE were judged as solely related to Modufolin. 31 patients have today been evaluated for efficacy. ORR 1st line patients (n=12) All 50% (6 PR, 6 SD) Patients with Modufolin dose ≥60 mg/m2 71% (5 PR, 2 SD) Patients with Modufolin dose ≥60 mg/m2 + oxaliplatin 100% (3 PR) Conclusions: The lack of need for metabolic activation makes Modufolin a better candidate than LV/L-LV for improved outcome of 5-FU-based chemotherapy regimens in mCRC. The ISO-CC-005 study evaluates Modufolin in combination with 5-FU, irinotecan, oxaliplatin ± bevacizumab in mCRC patients in 4 countries in Europe. The results, so far, for both safety and efficacy seems promising. Clinical trial information: NCT02244632.
Benefit of adjuvant treatment in stages II and III colon cancer: Experience at the Ramón y Cajal University Hospital.
Authors: Martinez Saez Olga , Barquín García Arantzazu Martínez , Saavedra Serrano Cristina , Corral de la Fuente Elena , Serrano Domingo Juan José , Martín Huertas Roberto , Villamayor Delgado Maria , LONGO FEDERICO , Reguera Puertas Pablo , Pachon Vanessa , Rodríguez Garrote Mercedes , Guillen Carmen , Carrato Alfredo , Ferreiro Monteagudo Reyes 
Published: January 2019

842 Background: The standard adjuvant treatment for patients with stage III colon cancer is 6 months with fluoropyrimidines and oxaliplatin. The Intergroup Trial INT-0035 was the first large-scale study to demonstrate a significant reduction in the risk of death with adjuvant FU plus levamisole in patients with stage III colon cancer. In the MOSAIC study, the addition of oxaliplatin to fluoropyrimidines in patients with resected stage II to III colon cancer showed OS and DFS benefit of oxaliplatin. However, no significant benefit was observed in either DFS or OS in patients with stage II disease, therefore the benefit of adjuvant chemotherapy is still controversial in those patients. Methods: We retrospectively included patients with stages II and III colon cancer that were operated between 2009 and 2014 in the University Ramón y Cajal Hospital from Madrid. We calculate DFS and OS at 48 months and we perform a multivariable Cox model analysis to estimate the benefit of the chemotherapy in each stage. The model was further adjusted by including the following confounders: ECOG-PS, number or removed nodes ( < 12 or ≥ 12), grade and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied > 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (281 stage II and 283 stage III). 259 received chemotherapy and 305 did not. The median follow-up in the entire cohort was 49 months. The median DFS and OS were not reached at the moment of the analysis. DFS and OS at 48 months were both 78.5%. Globally, chemotherapy did not improve DFS (HR 1.05, p: 0.83) but OS was significantly better (HR 0.47, p: 0.001). By stage, chemotherapy did not improve DFS in stage II (HR: 1.6, p: 0.2) nor OS (HR 0.76, p: 0.43). In stage III, chemotherapy showed a trend to improve DSF (HR: 0.61, p: 0.075) and did improve OS (HR: 0.31, p < 0.0001). Conclusions: The multivariable analysis showed a chemotherapy benefit in patients with stage III colon cancer, with a 39% reduction in the risk of recurrence and a 69% in the risk of death; however, in stage II patients these benefits were not found either in DFS or OS.
Liver and/or lung metastasectomy after cetuximab or bevacizumab+FOLFIRI chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Kim Sang-A , Kim Ji-Won , Suh Koung Jin , Kim Jin Won , Oh Heung-Kwon , Cho Jai Young , Kim Duck-Woo , Lee Keun-Wook , Cho Sukki , Kim Jee Hyun , Kim Kwhanmien , Kang Sung-Bum , Jheon Sanghoon 
Published: January 2019

843 Background: Some mCRC pts who have liver and/or lung metastases (LLMs) could achieve cure after palliative chemotherapy and conversion surgery (CS) including metastasectomy. Though targeted agents including bevacizumab and cetuximab significantly improved outcomes in mCRC pts, the effect of targeted agents on cure rate after CS has not yet been thoroughly investigated. Methods: We analyzed clinical data of mCRC pts who initially had unresectable LLMs regardless of their size and number and underwent first-line cetuximab or bevacizumab+FOLFIRI. Pts who had metastasis other than liver and lung were excluded. Results: From January 2013 to May 2016, 87 pts (male, 56) were consecutively enrolled: liver-limited metastasis in 42 pts (48.3%), lung-limited metastasis in 17 pts (19.5%), and both liver and lung metastases in 28 pts (32.2%). Median age was 62 years (range, 37-85). K-RAS or N-RAS mutation was detected in 39 pts (46.4%) and B-RAF in 2 pts (3.1%) among mutation evaluated pts. Among them, 35 pts (40.2%) received cetuximab+FOLFIRI and the others (N = 52, 59.8%), bevacizumab+FOLFIRI. Median follow-up time was 20.0 months (range, 1.9-49.1). Response rate was 65.7% in the cetuximab group (CET) and 42.3% in the bevacizumab group (BEV) ( p= 0.032). Median progression-free survival was 19.1 months (95% confidence interval [CI], 11.2-27.1) in CET and 14.1 months (95% CI, 11.5-16.8) in BEV ( p= 0.249). CS was performed in 24 pts (27.6%) after median 8.7 months (range, 2.5-27.3) after initiation of chemotherapy. In CET, 11 pts (31.4%) including 8 pts with partial response (PR) and 3 pts with stable disease (SD) underwent CS and all (100%) attained R0. In BEV, 13 pts (25%) including 6 pts with PR and 7 pts with SD received CS and 11 of them (84.6%) achieved R0. Among pts with R0 resection, median disease-free survival (DFS) was 8.8 months (95% CI, 4.9-12.7) in CET and 3.2 months (95% CI, 0.0-7.4) in BEV ( p= 0.326). Conclusions: A substantial proportion of pts could receive CS after cetuximab or bevacizumab+FOLFIRI chemotherapy. CET tended to show higher rate of CS. However, the median DFS after R0 resection was not significantly different between the two groups.
Clinical differences and prognostic factors in right and left colon cancer.
Authors: Onate-Ocana Luis F. , Beltran Leonora , Gonzalez-Trejo Sagrario , Carrillo Jose F. , Herrera-Goepfert Roberto , Carmona-Herrera Doris , Aiello-Crocifoglio Vincenzo , Gallardo-Rincon Dolores , Ruiz Garcia Erika 
Published: January 2019

846 Background: Clinical-Pathological and genomic differences between Right-colon cancer (RCC) and Left-colon cancer (LCC) have been reported, but there is not available information from Latin American countries. Methods: A retrospective cohort study was carried out in patients with RCC and LCC treated from January 1989 to December 2016, in a cancer referral center at Mexico City. Patients were assigned into groups according to the location of the neoplasm defined by colonoscopy. Comparison between groups was performed regarding demographic, clinical, histopathology or survival data, using the Student’s T or Squared chi tests, as appropriate. Multivariate analysis was performed employing the logistic regression model. Survival analysis was addressed using the Kaplan-Meier method, and results were compared using the Log rank test. Results: 1,619 patients were included in this analysis; 806 were women (49.8%) and 813 men (50.2%); mean age was 58.1 years old. RCC was registered in 871 cases (53.8%) and LCC in 748 (46.2%). RCC was significantly associated with low socioeconomic status, low body mass index (BMI), low hemoglobin, low serum albumin, and lower lymphocyte count than LCC. Distribution of TNM stages was similar between groups, as well as gender, age of presentation, comorbidities, surgical morbidity and mortality; 72.3% of RCC and 83.2% of LCC were well or moderately differentiated ( p< 0.0001). Mean lymph node retrieval was 19.3 (SD 14.6) for RCC and 15.7 (SD 13.1) for LCC ( p< 0.0001). Mean metastatic lymph node ratio was 0.19 for RCC and 0.21 for LCC ( p= 0.54). Median Overall survival (OS) was 5.55 years (95% CI 4.3–6.8) for RCC, and 3.28 years (95% CI 2.1–4.45) for LCC ( p= 0.052). Conclusions: Striking differences between RCC and LCC were found, mainly represented by anemia and immunonutritional variables. Moreover, OS is substantially better for RCC.
Early survival outcomes in stage I-III operated colon cancer patients from a low prevalence, lower-middle income country: The Indian experience.
Authors: Kothari Rushabh Kiran , Ostwal Vikas S. , Ramaswamy Anant , Gupta Tara Chand , Kumar Bairwa Sandeep , Kapoor Akhil , Kumar Amit , Ventrapati Pradeep , Ramadvar Mukta , Arya Supreeta , Kumar Suman , Patil Prachi , DeSouza Ashwin , Saklani Avanish 
Published: January 2019

857 Background: Data regarding survival and outcomes in operated colon cancer patients from a lower-middle income and low prevalence nation like India is scarce. Methods: Patients who underwent curative resection for non-metastatic, non-rectal colon cancer from January 2013 to December 2016 were retrospectively analyzed from a prospectively maintained database for baseline demographics, disease characteristics, adjuvant chemotherapy, recurrence free survival (RFS) and overall survival (OS). RFS and OS were calculated by Kaplan Meier method. Results: 505 patients underwent resection in the pre-defined time-period. Median age of the patients was 53 years (range: 17 – 87) and 339 patients (67.3%) were male. Patients with stage I, stage II and stage III disease were 43(8.6%), 233(46.1%) and 217(42.9%), respectively, while 12 patients(2.4%) were not adequately staged, though non-metastatic. Right sided colon cancers were more prevalent as compared to left sided (56% vs. 44%) and 41 patients (8%) had signet ring adenocarcinoma on cytomorphology. Median number of nodes retrieved during surgery was 22 nodes(range:1-96 ). Adjuvant chemotherapy was planned for 406 patients (80.4%), with the common regimens used being capecitabine-oxaliplatin, capecitabine , 5-fluorouracil – oxaliplatin and 5-fluorouracil in 280 (55.2%), 80 (16%), 34 (7%) and 6 patients (1.2%), respectively. Planned adjuvant chemotherapy was completed in 334 patients(82.3%; n = 406) with 27 patients (6%) required dose reduction. 35 patients (7%) required permanent cessation of adjuvant treatment due to chemotherapy related toxicity. With a median follow up of 21.8 months (range: 0-56),estimated 3 year RFS for the entire cohort was 86.2% and estimated median OS was 95.2%. Estimated RFS in stage I, Stage II, stage III patients were 90.3%, 89.5% and 78% respectively (p-0.006). Conclusions: Early survival outcomes with Stage I-III colon cancers in a low prevalence country like India appears to be comparable or potentially superior to outcomes published from high prevalence countries. Adjuvant chemotherapy in Stage II and Stage III colon cancers in a real world scenario in India appears to be well tolerated.
Survival results of hepatectomy followed by adjuvant chemotherapy with three months of capecitabine plus oxaliplatin for colorectal cancer liver metastases: A multicenter phase II study.
Authors: Satake Hironaga , Hashida Hiroki , Tanioka Hiroaki , Miyake Yasuhiro , Yoshioka Shinichi , Watanabe Takanori , Matsuura Masato , Kyogoku Takahisa , Inukai Michio , Kotake Takeshi , Okita Yoshihiro , Hatachi Yukimasa , Yasui Hisateru , Kotaka Masahito , Kato Takeshi , Kaihara Satoshi , Tsuji Akihito 
Published: January 2019

866 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, the IDEA collaboration reported that adjuvant chemotherapy with the three months of CapeOx after curative resection for stage III colon cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We conducted a multi-institutional, single-arm, phase II trial to confirm the feasibility of the three months of adjuvant CapeOx for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given with 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CapeOx consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). Among the 28 patients, 20 (71.4%: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3/4 toxicities were neutropenia (29%). No treatment related death was observed. With a median follow-up period of 36 months (range 15-53months), 3 year-relapse free survival was 75.3%. Conclusions: The three months of adjuvant CapeOx is tolerable for post curative resection of CLM. Clinical trial information: 000011164.
Clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for colorectal cancer.
Authors: Yagi Shusuke , Shinozaki Eiji , Chin Keisho , Suenaga Mitsukuni , Takahari Daisuke , Ogura Mariko , Ichimura Takashi , Wakatsuki Takeru , Ozaka Masato , Nakayama Izuma , MATSUSHIMA TOMOHIRO , Osumi Hiroki , Yamaguchi Kensei 
Published: January 2019

867 Background: CAPOX as adjuvant chemotherapy is a standard care option for stage III and high risk stage II colorectal cancer(CRC). And then chemotherapy induced diarrhea (CID) is known as one of the dose-limiting toxicities for CAPOX. Although diverting ileostomy is useful for preventing serious complications of high risk anastomosis, it is well recognized that high ileostomy output is hard to manage. Furthermore, the effect of diverting ileostomy on CID of adjuvant chemotherapy is unclear. In this study, we addressed the clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for CRC. Methods: Patients who diagnosed with stage III colon cancer and stage II or III rectal cancer after curative surgery and received CAPOX as adjuvant chemotherapy during 2011- 2014 were reviewed retrospectively. We investigated the relationship between diverting ileostomy and dose intensity, toxicities and disease-free survival (DFS). Results: 112 patients (median age 60 years, 52% male, 69% colon cancer, 63% stage III, median follow-up 47 months) were enrolled in this study. Of 112 patients, 100 patients were received chemotherapy without ileostomy (non-ileostomy group: NIG) and 12 patients were received chemotherapy with ileostomy (ileostomy group: IG). 112 Patients received 870 chemotherapy cycles. All treatment related grade 3/4 adverse events were documented in 39% of patients in NIG and 33% of patients in IG (P = 0.77). Grade 3/4 of CID occurred in 8% of patients in NIG and 8% of patients in IG (P = 1). Grade 3/4 of neutropenia were recognized in 21% of patients in NIG and 17% of patients in IG (P = 1). Average relative dose intensity (RDI) in NIG were 75.7% and 85.8% for capecitabine and oxaliplatin, respectively. Average RDI of capecitabine and oxaliplatin in IG were 76.1% and 82.7%, respectively. Significant difference of RDI of capecitabine and oxaliplatin were not shown in comparison between NIG and IG (P = 0.93, P = 0.63). The 3-year DFS rate was 85.0% in NIG and 75.0% in IG. The HR for DFS for NIG compared to IG was 1.709 (95% CI, 0.49 to 5.95; P = 0.40). Conclusions: The presence of diverting ileostomy does not affect RDI of CAPOX as adjuvant chemotherapy.
A prospective multicenter trial of S-1 with lafutidine vs S-1 as adjuvant chemotherapy for gastric cancer in Japan: AEOLUS.
Authors: Machida Nozomu , Terashima Masanori , Taku Keisei , Daimon Takashi , Kimura Masashi , Sugimoto Akihisa , Yasui Hirofumi , Nozaki Isao , Fukushima Norimasa , Takagane Akinori , Kim Yongil , Takiguchi Nobuhiro , Takagi Masakazu , Misawa Kazunari , Kimura Taisei , Maeda Masato , Kanai Toshikazu , Ota Mitsuhiko , Yokoyama Hidetarou 
Published: January 2019

91 Background: From the result of ACTS-GC study, adjuvant chemotherapy with S-1 for one year is standard therapy of gastric cancer in Japan. In this study, completion rate of pre-planned S-1 treatment was 65.8% and there is still room for improvement on this rate. Lafutidine is a H2 blocker and enhances submucosal blood flow via capsaicin-sensitive afferent neurons. Alleviating effect of lafutidine on toxicity of 5FU leading to discontinuation of adjuvant treatment could be expected. Methods: Patients with histologically confirmed stage II (excluding T1 cases), IIIA, or IIIB (Japanese Classification of Gastric Carcinoma 13th) who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 with lafutidine(L) or S-1 (S). All patients were given S-1 (40mg/m2) for 4 weeks with 2 weeks rest, repeated for 1 year after surgery. Patients of L group received lafutidine (20mg/day) every day for 1 year with S-1. The primary end point was treatment completion rate (TCR) of S-1. Definition of treatment completion was S-1 continuation for 1 year with over 70% planned dose. The secondary end points were toxicity (CTCAE v3.0) and relative total administration dose (RD) of S-1. Results: We randomly assigned 101 patients to the L group and 101 patients to the S group between February 2010 and December 2012 from 17 centers in Japan. After randomization, two patients were found to be ineligible in L group (the absence of cytologic examination of the peritoneal fluid, stageIB) and 1 in S group (allocation violation). TCR was 68.3% in the L group and 60.4% in the S group (p = 0.072, Cochran-Mantel-Haenzel test at a pre-specified one-sided significance level of 0.1). Adverse events of grade 3/4 excluding ineligible example was 30.0% in the L group, and 36.0% in the S group. Patients who require a dose reduction and/or delay of S-1 was 41.6% in the L group, and 51.5% in the S group. RD was 83.9% (range: 1.6-103.7) in the L group, and 84.0% (range: 1.7-103.8) in the S group. No any toxicity of lafutidine was observed. Conclusions: Lafutidine may increase a completion rate of adjuvant chemotherapy using S-1 within a 30% dose reduction for gastric cancer. This result need to be confirmed in double-blind placebo control study. Clinical trial information: UMIN000002703.
Nodal downstaging in gastric cancer in relation to survival when ypN0 is achieved.
Authors: Ikoma Naruhiko , Estrella Jeannelyn , Hofstetter Wayne Lewis , Das Prajnan , Ajani Jaffer A. , Fournier Keith F. , Mansfield Paul F. , Badgwell Brian D. 
Published: January 2019

93 Background: The AJCC 8th edition introduced ypStage for patients with gastric cancer due to the increasing use of preoperative therapy. ypN0 patients have better survival than ypN+ patients; however, whether patients who had clinically positive nodal disease before preoperative therapy (cN+ ypN0) have similar survival to those who had “natural N0” (cN0 ypN0) disease is unknown. Methods: We reviewed an institutional database to identify patients with gastric adenocarcinoma who underwent potentially curative R0 resection after preoperative chemo- or chemoradiation therapy. Patients were categorized into 3 groups based on nodal status: natural N0 (cN0 ypN0), downstaged N0 (cN+ ypN0), and ypN+. Univariable and multivariable Cox regressions were performed to determine associations with overall survival (OS). Results: We identified 316 patients who met study criteria, including 74 (23%) patients with GEJ tumors; 56% were white and 62% were male. Preoperative chemoradiation therapy was given to 239 (76%). Ninety-four (30%) had natural N0, 93 (29%) had downstaged N0, and 129 (41%) had ypN+ disease. Of all patients, 136 (43%) patients died during a median follow-up of 3.1 y. Median OS was 7.7 y, and 5-year OS was 60.3%. OS did not differ in patients with natural N0 disease (5-y OS, 72%) and those with downstaged N0 disease (5-y OS, 69%) ( p = 0.776), even though the downstaged N0 group had more advanced baseline cT disease than did the natural N0 group ( p < 0.001). On multivariable analysis adjusting for other factors, including ypT category, OS did not differ between natural N0 and downstaged N0 patients (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.54-1.48; p = 0.666), but it was shorter in ypN+ patients (HR, 1.82; 95% CI, 1.15-2.87; p = 0.010). Sensitivity analyses also showed equivalent OS in the natural N0 and downstaged N0 groups within the ypT0-2 group ( p = 0.936) and the ypT3-4 group ( p = 0.608). Conclusions: In patients with gastric cancer who underwent preoperative therapy, we found similar OS in patients with natural N0 and those with downstaged N0 disease. As ypN+ patients had poor OS, achieving ypN0 status is an important hallmark demonstrating the effectiveness of preoperative therapy.