bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival using local excision techniques with and without radiation compared with APR for stage I rectal cancer: A SEER based analysis
Authors: Wortham A. H. , Schreiber D. , Rineer J. , Katsoulakis E. , Sroufe R. , Marienberg E. , Nwokedi E. , Han P. , Choi K. , Rotman M. 
Published: August 2020

4032 Background: The standard of care for Stage I rectal cancer is radical resection. Increasingly, local therapies have been used to decrease morbidity and preserve sphincter control. Due to increased risk of local recurrence with less radical surgery, patients often receive adjuvant radiation. This analysis compares the outcomes of sphincter sparing treatment with radical surgery in Stage I rectal cancer. Methods: Using the Surveillance, Epidemiology and End-Results (SEER) registry, we performed a query of patients with Stage T1–2N0 (T=4 cm or less) rectal adenocarcinoma between 1988 and 2003 who were treated with either local excision alone (LE), local excision followed by radiotherapy (LE+RT) or abdominoperineal resection (APR). APR was selected as comparison group to select for a similar cohort of patients with distal tumors that would be eligible for LE. Kaplan-Meier analysis was performed to compare overall survival for patients receiving radical surgery versus local therapy. Subgroup survival analysis was performed by T-stage (T1 vs T2). Results: 2,144 patients were identified: 744 were treated with LE alone, 197 underwent LE+RT, and 1203 underwent APR. Patients undergoing LE ± RT had a median survival (MS) of 131 vs 121 months in the APR group (p=0.574). When comparing LE vs LE+RT, there was no difference in MS for the whole cohort (134 vs 108 months, p=0.39). However, on subgroup analysis there was a significant survival benefit in favor of LE+RT for T2N0 only (104 vs 74 months, p=0.048). For T1N0, the MS for LE+RT was 161 vs 147 months for LE (p=0.621). Comparing with APR, patients undergoing LE+RT had a MS of 108 vs 121 months in the APR group (p=0.684). For T1N0, the MS for LE+RT was 161 vs 153 months for APR (p=0.62). For T2N0 patients, the MS for LE+RT was 104 vs 114 months for APR (p=0.726). Conclusions: According to this analysis, there was no statistical difference in survival for patients with Stage I rectal carcinoma undergoing APR versus LE+RT. Selected patients with T1N0 may undergo local excision alone. However, patients with T2N0 disease should undergo adjuvant radiation after local excision. The risks and benefits of these treatment strategies should be weighed and treatment should be individualized. No significant financial relationships to disclose.
ACRIN 6664: Patient acceptance and preferance of CT colonography compared to optical colonoscopy for colon cancer screening
Authors: Siewert B. , Gareen I. , Vanness D. , Herman B. , Johnson C. D. , Gatsonis C. 
Published: August 2020

4034 Background: Colorectal cancer screening must be repeated on a regular basis. Understanding patient perceptions and willingness to be rescreened will help to determine future compliance rates. The purpose of this study was to compare National CT Colonography Trial (NCTCT) screening participant experiences with CT colonography (CTC) and optical colonoscopy (OC), willingness to return for each procedure, and procedure preference. Methods: NCTCT participants underwent a single bowel preparation (BP). Participants were scheduled to receive CTC, followed by sedation and OC. Participants were asked to complete a questionnaire two weeks post-exam on physical discomfort and embarrassment during BP, CTC and OC and willingness to repeat CTC and OC (with or without BP) at different time intervals. McNemar's Test and logistic regression were used for statistical analysis. Results: 2310 of 2600 patients (89%) responded (1224 women, 1086 men). Mean age was 58.39 years (range 50–86). The participant population was 85% Caucasian, 11% African American and 4% other. Severe discomfort was reported by 7.1% participants with BP, 6.3% with CTC, and 2.2% with OC. Severe embarrassment was reported by 1.6% participants with BP, 1.3% with CTC, and 0.7% with OC. Forty-six percent of participants preferred CTC, 27.4% reported no preference, and 24.9% preferred OC (p<0.001). Repeat screening with CTC is currently recommended every 5 years and with OC every 10 years. 80.5% of the participants were willing to be screened again with CTC in 5 years and 97.5 % were willing to be screened again with OC in 10 years (p<0.001). If the screening interval for CTC were extended to ten years, 93.7% of participants were willing to return for screening (p<0.001). If BP were unnecessary, 91.0% were willing to be rescreened with CTC in 5 years and 97.5% were willing to be rescreened with OC in 10 years (p<0.001). Conclusions: NCTCT participants preferred CTC to OC, but their willingness to undergo repeat CTC was limited by the shorter interval between screenings currently recommended for CTC as opposed to OC. Improvements in technology that would eliminate the need for bowel preparation or extend the recommended screening interval would likely improve adherence to recommended repeat screening. [Table: see text]
Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients
Authors: Glas A. M. , Roepman P. , Salazar R. , Capella G. , Moreno V. , Westerga J. , Kuppen P. J. , Simon I. , Van ’t Veer L. J. , Tollenaar R. 
Published: August 2020

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]
Concordance of K-Ras status between colorectal cancer (CRC) primaries and related metastatic samples considering clinicopathological features
Authors: Cejas P. , López-Gómez M. , Madero R. , De Castro J. , Casado E. , Belda C. , Larrauri J. , Barriuso J. , González-Barón M. , Feliú J. 
Published: August 2020

4053 Background: K-Ras mutations in CRC primaries may predict resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, but we don´t know its behaviour in metastatic tissue. The aims of this study were: 1) Evaluate the grade of concordance of K-Ras status between primary and related metastatic samples 2) Establish a correlation between k-ras status and individual clinicopathological features Methods: K-ras mutations were retrospectively analysed in primary tumours of 124 patients and 138 related metastatic sites. The primary tumour site was colon in 87 patients and rectum in 37. Sites of metastases were liver (115 samples,83.3%) and lung (23 samples,16.7%). Some patients underwent surgery several times. We analyzed K-Ras point mutations in codons 12 and 13 by direct DNA sequencing from paraffin-embedded tumour and studied its relation with 13 clinicopathological features Results: K-Ras mutation was observed in 42(33.6%) primary tumours and in 52(39.1%) related metastatic sites, being the grade of concordance between primary and metastatic sites of 93% (95% CI: 97.5–88.3%). Discordance was observed in 9 (7%) patients: in 2, K-Ras status was wild type in metastatic site and expressed a mutational pattern in the primary tumour; vice versa, in 7, the mutation status was detected in the metastases meanwhile primary tumour was wild type. We also found statistically significative differences in mutation patterns regarding the site of the metastasic tissue: K-ras mutations were detected in 13 lung samples (61.9%) and in 39 liver samples (34.8%) (p=0.028). Of all the clinicopathological features analyzed we confirmed an increase of mutated K-ras status in tumours which had presented as perforation (p=0.044). No other relation with clinicopathological data was detected Conclusions: With this observational analysis, we confirm the high concordance (superior to 90%) between primary and related metastatic sites in terms of K-Ras status; for the first time, we have reported a higher mutational pattern in lung metastases than in liver disease, founds that may have important relevance regarding clinical/treatment decisions. For the realization of this study we received a grant from Amgen. No significant financial relationships to disclose.
Phase II trial of chemotherapy with high-dose FOLFIRI plus bevacizumab in the front-line treatment of patients with metastatic colorectal cancer (mCRC) and genotype UGT1A1*1/ UGT1A1*1 or UGT1A1*1/ UGT1A1*28 (FFCD 0504 trial). Results of a planned interim analysis
Authors: Mitry E. , Bouché O. , Dahan L. , Bonnetain F. , Laurent-Puig P. , Aparicio T. , Etienne P. L. , Lecaille C. , Lafargue J. P. , Jouve J. L. ,   Fédération Francophone de Cancérologie Digestive (FFCD)
Published: August 2020

4065 Background: The antitumor efficacy of irinotecan may be dose dependent. In a recent phase II trial, the combination of high-dose irinotecan (260 mg/m2) with LV5FU2 regimen was feasible with an acceptable safety profile and promising efficacy data (Ducreux et al. Oncology 2008;74:17–24). The aim of this study was to evaluate the association of the high-dose FOLFIRI plus bevacizumab in patients (pts) selected on the UGT1A1 polymorphism, which could be predictive of the irinotecan toxicity. Methods: Pts with UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotypes and previously untreated mCRC were treated with bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1 and 5FU 2400 mg/m2 46h infusion D1–2 every 2 weeks. Using Bryant & Day design with OR (independent review, H0 ≤ 40%; H1 : ≥ 60%) and toxicity (gr 4 neutropenia or febrile neutropenia or gr3–4 diarrhea; H0 ≥ 20%; H1≤ 5% ) as primary endpoints; a total of 108 pts, 54 in each group, was required (alpha 5% and power 80%) with a planned interim analysis after the inclusion of 17 pts by group. The trial will be stopped at interim analysis if ≤ 7 pts had an OR and/or ≥ 3 pts had a severe toxicity. All analyses were performed in ITT. Results: At the time of interim analysis, done for group 1 when the 17th pt had a 6-months follow-up, 96 pts have been included (group 1: 40 pts, group 2: 46 pts). An objective response rate was observed in 9/17 pts but 7/17 pts had a severe toxicity (gr 4 neutropenia: 2 pts, febrile neutropenia: 2 pts, gr 3 diarrhea: 4 pts). Overall, 14/17 pts had a gr3–4 toxicity. There was no toxic death. According to interim analysis rules, the trial was closed to inclusion (for both groups) on December 16th 2008 for toxicity. The interim analysis for pts of group 2 is planned for February 2009 when the 17th patient will have a 6-months follow- up. Conclusions: High-dose FOLFIRI plus bevacizumab, although effective, was associated with a high toxicity rate among pts with UGT1A1 *1/*1 genotype. Complete tolerance, efficacy and survival results for all included patients will be presented at the meeting. [Table: see text]
Pharmacogenetic analysis of TS and UGT1A polymorphisms predictive for response and toxicity in Spanish patients with advanced colorectal cancer treated with first-line irinotecan and 5-fluorouracil
Authors: Martinez-Balibrea E. , Abad A. , Valladares M. , Martinez-Villacampa M. , Aranda E. , Marcuello E. , Benavides M. , Martinez-Cardús A. , Ginés A. , Manzano J. L. ,   Spanish Group for the Treatment of Digestive Tumors
Published: August 2020

4066 Background: The possible role of uridine diphosphate-glucuronosyltransferase 1A (UGT1A) and Thymidylate Synthase (TS) gene polymorphisms in predicting toxicity and outcomes in irinotecan/ 5-Fluorouracil (5FU)-treated patients is still controversial. The aim of this work was to determine whether UGT1A1, UGT1A7, and UGT1A9 as well as TS polymorphisms affect toxicities and/or outcomes of Spanish patients with advanced colorectal cancer (mCRC) Methods: A total of 149 patients with mCRC were treated either with weekly irinotecan plus high-dose 5FU (FUIRI) or biweekly irinotecan plus 5FU/Leucovorin (FOLFIRI) as first-line chemotherapy (Aranda E; Ann Oncol. 2008 Aug 20). Genomic DNA was extracted from peripheral blood and genotyped using allelic discrimination and direct sequencing. Chi-square test, Fisher's exact test and logistic regression were used to study the association of genotypes with toxicity and response. Log rank and cox regression were used in survival analysis. All statistical tests were two-sided. Results: According to TS 5’TRP genotypes, 79.3% of the 2R/2R patients responded to therapy while only 52.5% of 2R/3R or 3R/3R patients do so (HR=3.5; 95% CI=1.3- 9.1; p=0.009). TS genotypes were not associated with toxicity. UGT1A1*28 TA7/TA7 genotype was clearly associated with severe toxicity (HR=12.7; 95% CI=3.1–51.3; p=0.001) and diarrhea (HR=4; 95% CI=1.3–12; p=0.016) when compared to TA6/TA7 and TA6/TA6 genotypes. These patients also experienced more severe neutropenia (40% vs. 18.8%, p=0.087) and more frequent dose reductions (53.3% vs. 38.1%, p=ns). UGT1A7*3/*3 and UGT1A9–118(dT)9/9 were associated with severe diarrhea (50% vs. 27% p=0.032 and 43% vs. 23% p=0.012). When all non-favourable genotypes (TA7/TA7, *3/*3 and 9/9) were taken into account, there was a statistically significant association with severe diarrhea (HR=4.5; 95% CI 1.3–16.3; p=0.021), neutropenia (HR=3.5; 95% CI=1–12.7; p=0.047) and both (HR=12.4; 95% CI=2.8–54.2; p=0.001). Conclusions: Our data clearly link UGT1A genotypes with irinotecan-related severe toxicity. TS 5’TRP genotypes are predictive of response to irinotecan/5FU first-line chemotherapy. No significant financial relationships to disclose.
Predictive biomarkers to improve treatment of metastatic colorectal cancer (mCRC): Outcomes with cetuximab plus FOLFIRI in the CRYSTAL trial
Authors: Kohne C. , Stroiakovski D. , Chang-chien C. , Lim R. , Pintér T. , Bodoky G. , Stroh C. , Celik I. , Rougier P. , Van Cutsem E. 
Published: August 2020

4068 Background: KRAS oncogene mutation status is predictive of efficacy of cetuximab alone or combined with chemotherapy (CT) in mCRC. Previous data from the phase III CRYSTAL trial showed that adding cetuximab to FOLFIRI in first-line mCRC significantly improved the overall response rate (ORR) and progression-free survival (PFS) in pts with KRAS wild-type (wt) tumors. The serine-threonine kinase BRAF is a direct downstream effector of KRAS. Here, we report the influence of KRAS and BRAF status on mature overall survival (OS) data. Methods: DNA was extracted from archived tumor material where available from randomized pts. KRAS and BRAF mutation status (wt or mutant [mt]) was determined by quantitative PCR. Treatment arms were compared using two-sided log-rank tests (5% significance level) for PFS and OS, and the CMH test for best ORR. Results: The KRAS-evaluable cohort (n=540; 64.4% KRAS wt) was similar to the overall ITT group. In KRAS wt pts, adding cetuximab to FOLFIRI significantly increased the odds for tumor response nearly 2-fold, reduced the risk of progression by 32% and extended median OS from 21.0 months (mo) to 24.9 mo (details in Table ). KRAS mt pts did not benefit from cetuximab. Data on the impact of BRAF mutations on cetuximab activity will be presented at the meeting. In the FOLFIRI and cetuximab + FOLFIRI arms, 31.2% and 36.1% of pts, respectively, received no further line of therapy, while 25.4% and 6.2%, respectively, received EGFR antibody therapy. Conclusions: The benefits of adding cetuximab to CT were greater in KRAS wt pts than ITT pts for all clinically relevant endpoints. KRAS is a key biomarker for selecting a targeted therapy combined with standard CT in first-line mCRC. [Table: see text] [Table: see text]
Pegfilgrastim in colorectal cancer (CRC) patients (pts) receiving every-two-week (Q2W) chemotherapy (CT): Long-term results from a phase II, randomized, controlled study
Authors: Hecht J. R. , Pillai M. , Gollard R. , Dreiling L. , Mo M. , Malik I. 
Published: August 2020

4072 Background: Survival in advanced CRC is prolonged by adding oxaliplatin (Ox) and/or irinotecan (Iri) to Q2W 5-fluorouracil/leucovorin (5FU/LV). Combination therapy, however, has a higher incidence of febrile neutropenia (FN) and related toxicities. This study evaluated pegfilgrastim dosing on day 4 of Q2W regimens in CRC. Here we present long-term follow-up of these pts. Methods: Advanced CRC pts were randomized (1:1) to pegfilgrastim 6mg or placebo, which was stratified by CT regimen received: FOIL, FOLFOX, or FOLFIRI. We previously reported grade 3/4 neutropenia (primary endpoint) in 43% placebo and 13% pegfilgrastim pts in the 4-cycle treatment phase (odds ratio = 0.19, 95% CI: 0.10–0.37; p < 0.0001). After end of treatment, pts were followed long term for ≤ 2 years (inclusive of ≤ 8 additional cycles) for serious adverse events (SAEs), overall survival (OS), and progression-free survival (PFS). Median follow-up time was 519 days. Kaplan-Meier methods estimated OS and PFS from study day 1. The study was not powered to detect PFS or OS differences between treatment groups. Results: Of 241 pts analyzed (123 pegfilgrastim, 118 placebo), 49% received FOLFOX, 26% FOLFIRI, and 25% FOIL. In the treatment period, 8% placebo and 2% pegfilgrastim pts had grade 3/4 FN ( Table ). Pegfilgrastim was well tolerated with no dose delays attributed to leukocytosis. Pegfilgrastim and placebo had similar PFS and OS ( Table ). No SAEs related to study drug were reported in the follow-up period. Conclusions: In this randomized, placebo-controlled study, pegfilgrastim significantly lowered neutropenic risk. Bone pain incidence in this CRC population was lower than in breast cancer pts treated with a taxane (Vogel J Clin Oncol 2005); the incidence in pegfilgrastim pts was modestly increased over placebo. Leukocytosis was not a concern despite the 11-day dosing interval. Long-term results suggest similar PFS and OS in the pegfilgrastim and placebo pts in this CRC study. [Table: see text] [Table: see text]
Efficacy and safety of bevacizumab (BEV)-based combination regimens in patients with metastatic colorectal cancer (mCRC): Randomized phase II study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD 13/0503 study)
Authors: Ducreux M. , Adenis A. , Mendiboure J. , François E. , Boucher E. , Chauffert B. , Ychou M. , Pierga J. , Montoto-Grillot C. , Conroy T. 
Published: August 2020

4086 Background: The combination of BEV and chemotherapy is highly effective in patients with mCRC and improves response rate, progression-free survival and overall survival compared with chemotherapy alone. This randomized non-comparative phase II trial evaluated the efficacy and safety of BEV in combination with either XELIRI or FOLFIRI as first-line therapy for mCRC. Methods: Patients were eligible for inclusion in this study if they had histologically proven measurable mCRC, were aged 18–75 years, and had an ECOG performance status (PS) of 0–2. Patients were treated with 8 cycles of XELIRI (irinotecan 200 mg/m2 on Day 1 and capecitabine 1000 mg/m2 bid on Days 1–14) + BEV 7.5 mg/kg on Day 1, every 3 weeks or 12 cycles of FOLFIRI (irinotecan 200 mg/m2 on Day 1 + 5-fluorouracil (5-FU) 400 mg/m2 + folinic acid 400 mg/m2 on day 1 followed by 5-FU 2400 mg/m2 via 46-h infusion) + BEV 5 mg/kg on day 1, every 2 weeks. BEV was continued to disease progression. Patients aged ≥65 years received a lower daily dose of capecitabine (800 mg/m2 bid). The primary endpoint was crude progression-free survival (PFS) at 6 months. Results: In total, 145 patients were entered in the study between March 2006 and January 2008; 72 patients received BEV + XELIRI and 73 patients received BEV + FOLFIRI (male 64%/48%; median age 61/61 years; 35/36% aged >65 years). Preliminary results from the first 6 months of follow-up are reported here. A total of 491/783 cycles was administered, 63%/67% receiving at least the initially planned number of cycles (8 cycles for BEV + XELIRI and 12 for BEV + FOLFIRI). Main results are given in the table . Conclusions: This randomized non-comparative study has shown that BEV + XELIRI and BEV + FOLFIRI are similarly effective treatments for patients with mCRC, with manageable toxicity profiles. Results with updated follow-up will be presented at the Meeting. [Table: see text] [Table: see text]