bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Greek participitation to IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study of 3 versus 6 months of adjuvant chemotherapy in stage III colon cancer: Patients’ characteristics and safety analysis.
Authors: Souglakos John , Boukovinas Ioannis , Kakolyris Stylianos , Ziras Nikolaos , Androulakis Nikolaos E. M. , Ardavanis Alexandros , Kentepozidis Nikolaos K. , Vaslamatzis Michael , Athanasiadis Athanasios , Christopoulou Athina , Makrantonakis Paris , Polyzos Aristidis , Mavroudis Dimitrios , Mala Anastasia , Kalisperi Aggeliki , Xynogalos Spyros , Varthalitis Ioannis I. , Kouroussis Charalambos , Prinarakis Efthimios , Georgoulias Vassilis 
Published: March 2017

740 Background: The International Duration Evaluation of Adjuvant (IDEA) collaboration was established to prospectively analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines (FU)-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the Greek IDEA study was 1.000 patients. Methods: Greek IDEA randomized patients with stage III colon cancer between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to October 2015, 708 patients were randomized in Greek centers either to arm A (n = 354, 50%) or to arm B (n = 354, 50.%). 297 (41.9%) patients received mFOLFOX6 and 411 (58.%) XELOX. The median age was 67 years (20-75) and 579 (81.8%) of them had PS 0. The patients’ population was balanced for the major risk factor between the two arms: N1/N2 disease (68.1/31.9% vs. 68.9/31.1 for ARM A and B, respectively), obstruction (4.5% vs. 2.5 for ARM A and B, respectively) and perforation (5.1% vs. 6.2 for ARM A and B, respectively). Overall, 96.9% and 89.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 505 mg/m2 in arm A and 738 mg/m2 in arm B. Toxicity profiles were comparable between the two arm and the two fluoropyrimidines backbones with a total incidence of Grade 3/4 adverse events 18.9/4.4% and 19.7/5.1% for mFOLFOX6 and XELOX, respectively. Grade 2/3-4 peripheral neuropathy during the study was similar between arm A (33.9/4%) and B (38.7/3.7%). Conclusions: Both mFOLFOX6 and XELOX were safe. More patients completed the scheduled treatment in the 3-arm schedule.
Prognostic impact of primary tumor location in patients with metastatic colorectal cancer (mCRC) at the salvage lines.
Authors: Nagaoka Tomoyuki , Wakatsuki Takeru , Shinozaki Eiji , Nakayama Izuma , Suenaga Mitsukuni , Fukuda Naoki , Osumi Hiroki , Matsushima Tomohiro , Ichimura Takashi , Ogura Mariko , Ozaka Masato , Takahari Daisuke , Chin Keisho , Yamaguchi Kensei 
Published: March 2017

741 Background: Recently it has been suggested that primary tumor location may have a clinical impact on the front line chemotherapies; namely, right-sided tumor benefit less from cytotoxic and targeted agents compared with left-sided tumor. Regorafenib and TAS 102 have recently emerged and the prognostic impacts of tumor location on these agents are unknown. Methods: Clinical information of patients who were administrated Regorafenib and/or TAS 102 was retrospectively collected. Patients’ demographics by tumor location were compared using Fisher’s exact test. Time to treatment failure (TTF), and overall survival (OS) by tumor location were calculated using Kaplan-Meyer Methods and compared using Log-rank test. In addition, subgroup analyses were performed to see the interactions between tumor location and covariates in each agent. All tests were performed at the two-sided .05 significance level. Results: The median TTF (mTTF) and OS (mOS) were 2.0 and 8.0 months in the regorafenib group (n = 98) and were 2.4 and 7.9 months in the TAS102 group (n = 95), respectively. In the regorafenib group, 71 patients had a left-sided tumor and 27 patients had a right-sided tumor. In the TAS102 group, 64 patients had a left-sided and 31 patients had a right-sided tumor. There was no significant difference between right and left sides in both groups with the exception that a greater number of older patients was seen in right-sided in the TAS102 group. No significant difference of TTF and OS by primary site were observed in regorafenib (HR 0.92, 95% CI 0.68-1.70, P = 0.71 for TTF, HR 1.09, 95% CI 0.68-1.81, P = 0.74 for OS) and in TAS 102 (HR 0.84, 95%CI 0.53-1.36, P = 0.48 for TTF, HR 1.26, 95% CI 0.72-2.33 P = 0.43 for OS). Significant interactions were shown between presence of liver metastasis and tumor location both in TTF and OS in regorafenib (p < 0.05). On the other hand, in TAS102, significant interactions were shown between period from 1st line chemotherapy and tumor location in TTF and between time to metastasis and tumor location in OS (p < 0.05). Conclusions: In contrast to front line chemotherapy, no clinical impact of tumor location was demonstrated at the salvage lines in mCRC.
Efficacy of bevacizumab in combination with doublet chemotherapy as first-line therapy in metastatic colorectal cancer according to KRAS status.
Authors: Murai Katsuyuki , Masuishi Toshiki , Taniguchi Hiroya , Hamauchi Satoshi , Sugiyama Keiji , Tsushima Takahiro , Mitani Seiichiro , Todaka Akiko , Honda Kazunori , Yokota Tomoya , Narita Yukiya , Machida Nozomu , Kadowaki Shigenori , Fukutomi Akira , Ura Takashi , Onozawa Yusuke , Ando Masashi , Yasui Hirofumi , Muro Kei , Yamazaki Kentaro 
Published: March 2017

744 Background: Bevacizumab (BV) plus fluoropyrimidine-based chemotherapy is a standard treatment as first-line therapy for metastatic colorectal cancer (mCRC). In phase 3 studies, addition of BV to doublet chemotherapy significantly improved progression-free survival (PFS), otherwise overall survival (OS) differences didn’t reach statistical significance. There are only a few reports that assess the efficacy of BV containing chemotherapy according to KRAS status. Methods: We retrospectively reviewed the data of mCRC patients who received doublet chemotherapy (FOLFOX/CapeOX/SOX/FOLFIRI/IRIS) with or without BV as first-line therapy in Aichi Cancer Center or Shizuoka Cancer Center between Apr. 2007 and Aug. 2014. Patients fulfilled following criteria: histologically proven adenocarcinoma, ECOG PS 0-1, adequate organ functions. Exclusion criteria were as follows: KRAS status unknown, adjuvant chemotherapy within less than 6 months (M) before relapse, doublet chemotherapy with other biologics. We analyzed the efficacy of doublet chemotherapy with BV (Group A) and without BV (Group B), dividing into KRAS exon 2 wild type (WT) and mutant (MT). WT-A means Group A in WT. Results: Patients met the selection criteria were 578 (WT-A/WT-B 276/55, MT-A/MT-B 202/45). Patients’ backgrounds were as follows; median age (range) 63 (20-88) years old, male/female 60/40%, ECOG PS 0/1 66/34%, tumor location right colon/left colon and rectum 29/71%, number of metastases 1/ ≥ 2 48/52%, KRAS status WT/MT 57/43%. PFS in Group A/B was 13.0/8.4 m (HR 0.49, 95%CI 0.39-0.61, p < 0.0001), and OS was 32.4/27.1 m (HR 0.70, 95%CI 0.56-0.88, p = 0.0024). PFS was 12.7/8.5 m in WT-A/WT-B (HR 0.51, 95%CI 0.38-0.69, p < 0.0001), 14.5/8.0 m in MT-A/MT-B (HR 0.46, 95%CI 0.33-0.64, p < 0.0001). OS was 32.6/29.8 m in WT-A/WT-B (HR 0.85, 95%CI 0.62-1.17, p = 0.32), 31.7/25.8 m in MT-A/MT-B (HR 0.55, 95%CI 0.39-0.77, p = 0.0005), adjusted HR (variables: age, sex, ECOG PS, tumor location, et al) was 0.74 in WT (95%CI 0.53-1.05, p = 0.089), 0.69 in MT (95%CI 0.48-1.00, p = 0.047). Conclusions: Addition of BV to doublet chemotherapy as first-line therapy might prolong OS in patients with mCRC regardless of KRAS status.
A prospective, randomized study of low molecular weight as supplemental therapy in metastatic colorectal cancer patients treated with FOLFIRI regimen and target agents.
Authors: Tsai Hsiang-Lin , Tai Chi-Jung , Huang Ching-Wen , Wang Jaw-Yuan 
Published: March 2017

746 Background: Fucoidan is recently studied for its anti-cancer and anti-inflammatory effects. It also has been used as food supplements in Asia for many years. This study is the first prospective, randomized trial to compare the clinical outcomes and adverse events in metastatic colorectal cancer (mCRC) patients, who are treated with FOLFIRI regimen and target agents as the first line setting with or without low molecular weight Fucoidan (LMF). Additionally, the study also aimed to evaluate the inhibitory effect of LMF in EGFR-KRAS-BRAF-ERK signaling pathway. Methods: A total of 54 patients with mCRC were randomly divided into a study group (28 cases, 4g BID oral low molecular weight Fucoidan powder) and a control group (26 cases, 4g BID oral placebo powder). The supplements were given for 6 months during the therapeutic period. The primary endpoint was the disease-control rate (DCR), and the secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects between the two groups. MTT cell viability assay and western blotting analysis were used to evaluate synergic effect of LMF plus 5-FU or Cetuximab on Caco-2, SW620 and HCT-15. Results: 54 mCRC patients were enrolled, including 28 patients in the study group and 26 patients in the control group. The DCR was 92.8% vs. 69.2% in study and control group respectively ( P = 0.026) in median follow up time of 11.5 months. The PFS was 15.93 ± 1.20 vs. 10.80 ± 1.06 months ( P = 0.075), ORR was 60.7% vs. 46.2% ( P = 0.284) and OS was 18.04 ± 0.91 vs. 12.96 ± 0.83 months ( P= 0.092). There were no statistical differences in adverse effects between two groups. In vitrostudy, LMF plus 5-FU or Cetuximab showed synergic cytotoxic effect (maximal 24% increase) through the inhibition of the expression of p-EGFR, p-ERK and p-Akt. Conclusions: The preliminary results show that LMF as supplemental therapy in mCRC patients may improve DCR. In vitro, Fucoidan showed the synergic cytotoxic effect with 5-FU or Cetuximab. The possible mechanism may involve the inhibition effect of Fucoidan in phosphorylation of EGFR-KRAS-BRAF-ERK signaling pathway.
Effect of multidisciplinary tumor conference on clinical management of rectal cancer.
Authors: Karagkounis Georgios , Stocchi Luca , Lavery Ian C. , Liska David , Gorgun Emre , Amarnath Sudha , Khorana Alok A. , Kalady Matthew 
Published: March 2017

749 Background: Presentation of rectal cancer cases at a multidisciplinary tumor conference (MTC) is a required standard for the newly formed National Accreditation Program for Rectal Cancer. However, its impact on clinical decision-making remains incompletely defined. Our aim was to determine the frequency and manner in which MTC changed the management of patients with rectal cancer at a tertiary academic center. Methods: All rectal cancer cases presented at the weekly Colorectal Cancer MTC between July 2015 and June 2016 at a single institution were prospectively included. Patient demographics and clinical information were recorded. The presenting physician completed a uniform written questionnaire outlining their plan before and after the MTC discussion, and any changes in management as a result of the discussion. Imaging and pathology were reviewed for each case at MTC and consistency with prior interpretation was recorded. Results: 234 unique initial rectal cancer cases were included. Survey responses were obtained for 212 cases (90.6%). The mean patient age was 58.3 years. 37 patients (15.8%) presented with Stage IV disease and 20 (9.4%) had locally recurrent cancer. There was a documented change in plan as a result of the MTC discussion in 70 of 212 (33%) cases surveyed, including 22 cases (10.4%) in which the presenting physician had a “definitive plan” prior to the MTC. Changes in management included a change in therapy or change in therapy sequence in 45 cases (64%), and recommendation of further evaluation in 26 cases (37%). Change in management following MTC did not vary by surgeon experience: it occurred in 31.4%, 37.2% and 29.8% of cases presented by surgeons with < 10, 10-20, and ≥ 20 years of experience respectively (Chi-square p= 0.71). The imaging or pathology review at MTC resulted in a different interpretation than previously reported in 23% and 12% of cases, respectively. Conclusions: MTC changes clinical management for a significant portion of rectal cancer patients at a tertiary care center, independent of the presenting surgeons’ years of clinical experience. Our results highlight the utility of multidisciplinary rectal cancer care and support the MTC standard for the National Accreditation Program for Rectal Cancer.
Comparison of early tumor shrinkage between oxaliplatin plus S-1 and cisplatin plus S-1 in first-line chemotherapy with advanced gastric cancer.
Authors: Osumi Hiroki , Takahari Daisuke , Shinozaki Eiji , Chin Keisho , Ogura Mariko , Nakayama Izuma , Matsushima Tomohiro , Wakatsuki Takeru , Ichimura Takashi , Suenaga Mitsukuni , Yamaguchi Kensei 
Published: March 2017

75 Background: Early tumor shrinkage (ETS) is regarded as predictive marker in metastatic colorectal cancer. In the phase III study comparing oxaliplatin plus S-1 (SOX) to cisplatin plus S-1 (SP) in patients with advanced gastric cancer (AGC), although response rates were almost same between two groups, ETS wasn’t evaluated. Therefore, in AGC, it is controversial whether ETS is predictive or not and which is more suitable regimen, especially as neo adjuvant chemotherapy (NAC). The aim of this study is to compare ETS in SOX with SP and to evaluate the relationship between ETS and clinical outcomes in AGC. Methods: We retrospectively enrolled consecutive 469 patients (SOX 128, SP 341) with histopathologically confirmed HER2 negative AGC treated as 1st-line chemotherapy or NAC in our institution between January 2010 and June 2016. ETS was defined relative change in the sum of the longest diameters of target regions at week 8 (±4) compared to baseline. (Cut-off: 20%). Tumor response was assessed computed tomography using the RECIST 1.1. Patients with peritoneal metastasis and/or bone metastasis without target region were excluded in this study. Results: 192 patients (SOX 60, SP 132) were included in this study. Median tumor shrinkage between SOX and SP were 30% (min-35%, max77%) and 21% (min-89%, max73%), respectively ( p= .16). The ratio of ETS between SOX and SP was 53.3% and 50.7%, respectively ( p= .75). ETS > 20% was associated with longer OS and PFS when compared with ETS≦20% in SOX group. (ETS > 20% vs≦20%: OS 15.3 vs 10.1 months, HR 0.47 p= .03 PFS 7.6 vs 4.2 months, HR 0.58 p= .09) On the other hand, ETS > 20% was associated with significantly longer PFS only when compared with ETS≦20% in SP group and significant independent predictive factor. (ETS > 20% vs≦20%: OS 15.7 vs 10.9 months, HR 0.79 p= .29 PFS 7.7 vs 4.0 months, HR 0.57 p= .01) In multivariate analysis, ETS remained significant independent predictive factor for PFS in SP group (HR 0.53, p= .006). Conclusions: The ratio of ETS was similar between SOX and SP. ETS may be an early-on-treatment predictor in AGC.
Nonagenarian patients with metastatic colorectal cancer: Results from the South Australian metastatic colorectal cancer registry.
Authors: Price Timothy Jay , Karapetis Christos Stelios , Piantadosi Cynthia , Padbury Robert , Roy Amitesh Chandra , Maddern Guy , Gonzalo Tapia Rico , Moore James , Roder David , Townsend Amanda Rose 
Published: March 2017

752 Background: With improved healthcare we now face an ageing population worldwide. More patients with metastatic colorectal cancer (mCRC) will present at advanced age. Patients with mCRC now have the potential of living longer due to surgery, chemotherapeutic agents and monoclonal antibodies. Australian data (2011) indicated 1.3% of the population are aged over 90 years*. Medical oncologists are now being referred patients in their 90’s and the optimal management for this group is unknown. Methods: The population based South Australian Clinical Registry for mCRC includes all patients with metastatic CRC diagnosed since the 1st February 2006. We examined cancer characteristics, treatments administered and outcomes for patients aged > 90 years. Results: 130 patients of 4199 (3%) were aged 90 years or older. The median age was 92.1 years (range 90-104.8 years). 61% were female, 70% presented with synchronous disease. Organ involvement was as follows; 58% liver, 32% lung, 8% peritoneal and 7% bone. Primary site was: right 46%, left 28%, rectum 20%, unknown 6%. Only 4 patients had KRAS testing (all WT). 44.6% overall have had no surgery for their CRC primary. 24% of those with synchronous disease at diagnosis had resection of primary lesion and 3% had stoma formed for palliation. One patient had lung resection for metastasis. Only 4 patients received systemic therapy (age range 90-93). Lines of therapy delivered; one in 2 patients, two lines in one and 4 lines in one. Aside single agent 5FU, combination therapy (oxaliplatin/FU+/- bevacizumab) was given to two patients and cetuximab single agent in 2 (WT one, unknown one). The median survival overall was 3 months (95% CI 1.4-4.6 months). Two year survival was 10%. Conclusions: This analysis gives us some insight into the management of the very old. Female sex and right sided cancers are more frequent. Systemic therapy is rarely offered and the outlook is poor. Further research to understand whether active therapy is possible or warranted in this age group should be considered. *http://www.abs.gov.au/ausstats/abs@.nsf
A phase I/II study of nintedanib and capecitabine in refractory metastatic colorectal cancer.
Authors: Boland Patrick McKay , Fakih Marwan , Attwood Kristopher , Robins Melissa , Iyer Renuka V. , Ma Wen Wee 
Published: March 2017

759 Background: Refractory metastatic colorectal cancer patients (mCRC) have a poor prognosis with median survival of 4-6 months. Nintedanib is a TKI which inhibits VEGFR, PDGFR, and FGFR with preclinical efficacy in bevacizumab resistant CRC. This phase I/II study sought to evaluate the recommended phase II dose (RP2D) and efficacy of nintedanib and capecitabine in refractory mCRC patients. Methods: Key eligibility criteria included histologically proven mCRC, ECOG PS of 0 or 1, progression/intolerance to a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy for RAS wt patients. Prior regorafenib, uncontrolled hypertension ( ≥ 160/90), recent clinically significant thrombosis/hemorrhage, or prior intolerance to capecitabine were exclusionary. Doses were escalated across 2 planned dose levels (DL) in a standard 3+3 design, with escalating doses of capecitabine. DLT observation window was the first 3 weeks after dosing. The primary endpoint was establishment of the RP2D. Results: 10 patients were enrolled across 2 dose levels. 1 patient withdrew consent and was replaced. 5 (50%) were PS 0. No grade 4 or 5 AEs were observed. No DLTs were observed. 2/10 (20%) of patients experienced a grade 3 AE, including hyperbilirubinemia (10%), AST elevation (10%), diarrhea (10%), dehydration (10%), and weakness (10%). The most common treatment-related AEs included palmar-plantar eythrodysesthesia (PPE) (50%), diarrhea (40%), stomatitis (30%), nausea (20%), vomiting (20%), and fatigue (20%). The RP2D was determined to be capecitabine 1000 mg/m2 divided bid and nintedanib 200 mg bid. PK data will be presented. Conclusions: Treatment was well tolerated. Most of the observed AEs were grade 1 or 2, without a marked difference between DLs. PPE was readily managed with dose adjustments. The phase II study is ongoing at the RP2D. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02393755.
Tumor-size-based endpoints as surrogates for overall survival in the ARCAD Advanced Colorectal Cancer Database.
Authors: Burzykowski Tomasz , Coart Elisabeth , Saad Everardo D. , Sargent Dan , Zalcberg John Raymond , Shi Qian , Sommeijer Dirkje Willemien , Buyse Marc E. 
Published: March 2017

766 Background: Tumor-size-based endpoints such as depth of response have recently become a focus of investigations related to search for early on-treatment predictive markers for patients with colorectal cancer (Piessevaux et al. 2013; Cremolini et al., 2015; Heinemann et al., 2015). We evaluate the use of time-to-nadir (TTN) and depth-of-nadir (DoN) as potential surrogates for overall survival (OS). Methods: We have used the data from trials included in the ARCAD Advanced Colorectal Cancer Database. We have considered three sets of treatment comparisons: comparisons involving only chemotherapy agents (CT); involving anti-angiogenesic agents (ANG); and involving anti-EGFR agents (EGFR). For each of the sets separately, we applied a two-stage modelling approach (Renard et al. 2002) to jointly analyze the relative change of tumor size versus baseline (RCTS) and OS. In particular, in the first stage, a joint model for the repeated measurements of RCTS and OS was fitted to the data. Based on the model, treatment effects on OS and RCTS were estimated. Treatment effects on OS were expressed as log-hazard-ratios, while the effects on RCTS were expressed in terms of differences in the time-to-nadir (TTN) and in the depth of nadir (DoN). In the second stage, a linear regression was fitted through the estimated treatment effects on TTN/DoN and OS. The coefficient of determination (R2), computed by using the comparison-specific sample-size as weights, was used to quantify the strength of association between the treatment effects on TTN/DoN and OS. In particular, values of R2 larger than 0.75 were considered as indicating a good surrogate. Results: The CT set included 18 comparisons with 5726 pts. in total. For the treatment effects on TTN and OS, the value of R2 was estimated to be equal to 0.31, while for DoN and OS, it was equal to 0.01. For the ANG set (11 comparisons, 3964 pts.) the values of R2 were equal to 0.26 and 0.21, respectively, while for the EGFR set (16 comparisons, 4687 pts.) they were equal to 0.10 and 0.45, respectively. Conclusions: These preliminary results suggest that TTN and DoN are not good surrogates for OS in advanced colorectal cancer. More detailed analyses are ongoing and will be presented at the meeting.