bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular aspirin (ASA) use and survival in patients with PIK3CA-mutated metastatic colorectal cancer (CRC).
Authors: Kothari Nishi , Kim Richard D. , Gibbs Peter , Yeatman Timothy Joseph , Schell Michael J. , Desai Jayesh , Tie Jeanne , Lipton Lara Rachel , Jorissen Robert N. , Wong Hui-Li , Sieber Oliver , Day Fiona , Faragher Ian , Jones Ian , Tran Ben 
Published: February 2017

386 Background: Recent data has demonstrated that regular ASA use improves overall and cancer-specific survival in the subset of CRC patients harboring PIK3CA mutations. However, as this series only analyzed 15 PIK3CA mutant CRC patients with metastatic disease at diagnosis, it remains uncertain whether the survival benefit associated with regular ASA use extends to patients with metastatic disease. We combined data from two large academic institutions to explore the association between regular ASA use and survival in metastatic CRC. Methods: Patients with PIK3CA mutated CRC were identified at Moffitt Cancer Center (MCC) in Tampa, FL and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data (including age, sex, site of disease) and survival data were available. At MCC, PIK3CA mutations were identified by exome sequencing using an Illumina Next Generation Sequencing platform with 50-100X coverage. At RMH, Sanger sequencing was used to identify PIK3CA mutations. Survival analyses were conducted using Cox regression. Results: We identified 187 CRC patients who harbored a PIK3CA mutation. Median age was 72 years and median follow up was 48 months. 49 (26%) patients used ASA regularly. 47 (25%) patients had metastatic disease at diagnosis. In univariate analyses, regular ASA use was not associated with improved overall survival (HR 0.87, p = 0.60), although there was a trend towards improved cancer-specific survival (HR 0.48, p = 0.06). In patients with stage-II or stage-III disease, regular ASA use did not improve overall, cancer-specific or recurrence-free survival. However, in stage-IV patients, regular ASA use was significantly associated with improved overall (HR 0.35, p = 0.04) and cancer-specific (HR 0.28, p = 0.02) survival in a univariate analysis. Conclusions: Our study demonstrates that in patients with metastatic CRC harboring a PIK3CA mutation, regular ASA use is associated with a significant overall and cancer-specific survival advantage. However, we were not able to confirm the survival advantage across all stages. To our knowledge, our study is the largest to examine ASA use in PIK3CA mutated CRC.
Predictors of pathologic complete response after neoadjuvant treatment for rectal cancer: A multicenter study.
Authors: Armstrong Dawn Elizabeth , Raissouni Soundouss , Price Hiller Julie A. , Mercer Jamison , Powell Erin Diana , MacLean Anthony , Jiang Maria , Doll Corinne M , Goodwin Rachel Anne , Batuyong Eugene , Zhou Kevin , Monzon Jose Gerard , Tang Patricia , Heng Daniel Yick Chin , Cheung Winson Y. , Vickers Michael M. 
Published: February 2017

397 Background: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective population based study in four Canadian provinces. Methods: Cancer Registries identified consecutive patients with clinical stage I-III rectal cancer from the Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and the Dr. H. Bliss Murphy Cancer Centre who received fluoropyrimidine-based CRT and had curative intent surgery (Sx) from 2005 to 2012. Patient, tumor, and therapy characteristics were correlated with response. Results: Of the 891 patients included, 885 patients had pCR data available. 161 (18.2%) had a pCR to CRT, while 724 (81.8%) did not. Patients with a pCR had a lower pre-treatment (tx) CEA, and higher hemoglobin on univariate analysis (see table). On multivariable analysis, statin use at baseline (OR 1.7, 95% CI 1.04-2.89, p=0.044), lower pre-tx CEA (OR 1.03, 95% CI 1.003-1.05 p=0.028) and distance closer to anal verge (OR 1.07, 95% CI 1.004-1.15, p=0.039) were significant predictors of pCR. The 3yr DFS was 86% in those with pCR vs 62.5% in those without a pCR (P<0.0001). Conclusions: Lower pre-tx CEA, distance closer to anal verge and statin use are predictors of pCR. Clinical trials investigating statins combined with neoadjuvant CRT may be warranted. [Table: see text]
Outcomes of adjuvant chemotherapy (AC) in young (YP) and elderly patients (EP) with high-risk stage II colon cancer (CC).
Authors: Kumar Aalok , Kennecke Hagen F. , Lim Howard John , Renouf Daniel John , Gill Sharlene , Woods Ryan , Speers Caroline , Cheung Winson Y. 
Published: February 2017

398 Background: High-risk stage II CC is defined as those presenting with T4 stage, obstruction or perforation, <12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. Our prior findings suggest that improved outcomes from AC are limited to specific high-risk features, such as T4 disease (Kumar et al, ASCO 2012). It is unclear if this benefit is seen across all ages. Our aim was to compare patterns of AC use and outcomes in YP and EP with high-risk stage II CC. Methods: All patients diagnosed with high-risk stage II CC from 1999 to 2008 and evaluated at any 1 of 5 regional cancer centers in British Columbia were categorized into YP (age <70 years) or EP (age >/=70 years). Kaplan-Meier methods and Cox regression were used to correlate receipt of AC with overall survival (OS), disease specific (DSS), and relapse-free survival (RFS), stratified by age group. Results: A total of 1,236 patients were identified: 636 (51%) YP and 600 (49%) EP among whom 363 (57%) and 85 (14%) received AC, respectively. Individuals who received AC in either age group had better performance status than those who did not (ECOG 0/1 47% vs. 34%, p=0.02). After adjusting for known prognostic factors, a significant advantage in OS, but not DSS or RFS, from AC was observed for both YP and EP (Table). The impact of AC on these outcomes was similar across age groups (p interaction of age and treatment = 0.46, 0.64, and 0.69 for OS, DSS, and RFS, respectively). In the entire cohort, individuals with T4 lesions had significantly improved OS (HR 0.50, 95%CI 0.33-0.77, p=0.002), DSS (HR 0.59, 95%CI 0.37-0.93, p=0.03), and RFS (HR 0.63, 95%CI 0.42-0.95, p=0.03). The effect of AC in the T4 subgroup was also similar for both YP and EP in terms of OS, DSS and RFS (p interaction of age and treatment = 0.41, 0.71, and 0.77, respectively). Conclusions: In this population-based cohort of high-risk stage II CC, improvements in outcomes from AC were seen mainly in those with T4 disease, regardless of age. [Table: see text]
Prevalence of KRAS, BRAF, NRAS, PIK3CA, and PTEN alterations in colorectal cancer: Analysis of a large international cohort of 5,900 patients.
Authors: Basu Gargi Dan , Xiu Joanne , Arguello David , Feldman Rebecca A. , Millis Sherri Z. , Bender Ryan P. , Gatalica Zoran , Paul Les , Braiteh Fadi S. 
Published: February 2017

399 Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with metastatic disease accounting for 40 to 50% of newly diagnosed patients. EGFR monoclonal antibodies (Mab), cetuximab and panitumumab, are effective treatment for KRAS wild type CRC. Although mutations in KRAS predict resistance to EGFR Mab therapy, only 80% of CRC patients with KRAS wild-type (WT) status respond to treatment. This study is a retrospective evaluation of genomic alterations in the EGFR pathway such as alterations in KRAS, BRAF, NRAS, PIK3CA and PTEN that may predict lack of response to EGFR Mab therapy in CRC patients. Methods: A large database of 5,900 consecutive CRC patients was analyzed from 2011 onwards for demographics (sex, age, geography, site of tumor) and biomarkers that might correlate with response to EGFR Mab therapy. Comprehensive testing included gene sequencing for KRAS, BRAF, NRAS, PTEN, and PIK3CA (next-generation sequencing, Sanger, pyrosequencing) and immunohistochemistry for PTEN protein expression. Results: Analysis revealed the incidence of KRAS mutation of 42% which is consistent with published literature. Analysis of the KRAS WT cohort revealed a mutation rate of 13.8 % for BRAF, 6.8% for NRAS, and 40% for patients with either PTEN loss of expression/mutation or a PIK3CA mutation. Earlier studies support that mutations in NRAS, BRAF and activation of the PI3K pathway by PTEN/PIK3CA analysis result in lower response rates to EGFR Mab therapy in CRC. Furthermore, multiplex biomarker testing revealed the rare occurrence of concurrent mutations: 1/5,900 subject harboring a BRAF and NRAS mutations, 7/5,900 others with BRAF and PIK3CA mutations, and 8/5,900 subjects with NRAS and PIK3CA mutations. Conclusions: This is a comprehensive analysis of a large international cohort evaluating the prevalence of predictive molecular aberrations suspected of lack of response to EGFR Mab therapy in patients with WT KRAS. Prospective controlled studies are in progress to validate the role of BRAF, NRAS, PIK3CA, and PTEN in clinical management of CRC. It is imperative to further explore the molecular pathology of CRC beyond KRAS in patient selection for EGFR Mab therapy.
False-positive elevations of carcinoembryonic antigen in patients with a history of resected colorectal cancer.
Authors: Litvak Anna Maria , Cercek Andrea , Segal Neil Howard , Reidy Diane Lauren , Stadler Zsofia Kinga , Yaeger Rona D. , Kemeny Nancy E. , Weiser Martin R. , Pessin Melissa , Saltz Leonard 
Published: February 2017

403 Background: Routine monitoring of carcinoembryonic antigen (CEA) is standard practice in patients with a history of resected colorectal cancer. While it is known that false positive elevations of CEA can occur, the incidence of false positives and the upper limits of false positive elevations have not been previously well characterized. We evaluated these factors retrospectively in a large, single center, 10-year experience. Methods: Computerized medical records of Memorial Sloan-Kettering were searched electronically and then manually confirmed to identify patients who underwent an R0 resection of local-regional colorectal cancer between January, 2003 and December, 2012 and who had a rise in CEA above the normal range after a normal perioperative CEA. CEA elevations were regarded as false-positive if workup failed to identify the source of the CEA with at least 1 year follow up after the CEA first became abnormal. Results: 728 patients were identified who met all inclusion criteria. Of these, 358 patients (49%) were determined to have had a false-positive CEA elevation, 335 patients (46%) had a true-positive CEA elevation indicative of recurrent colorectal cancer, and 35 patients (5%) had a true positive CEA elevation indicative of development of a new, non-colorectal malignancy. Of those with false elevations, 111 had a single isolated CEA elevation (median highest CEA of 5.5ng/ml, range: 5.1-45.2ng/ml) with no further abnormal CEAs, while 247 had CEA elevations on two or more readings with median highest CEA of 6.7 (range: 5.2-34.9ng/ml). Of these 247 patients with confirmed false-positive CEA elevations, only 5 patients (2%) were above 15ng/ml and no confirmed CEA elevation over 35ng/ml was a false positive. Conclusions: False positive CEAs in the 5-15 range are relatively common. Confirmation of CEA elevation in this range prior to initiating imaging studies may be appropriate. False positive CEAs above 15 are rare. In our large data set, all CEAs above 35 were associated with actual cancer recurrence; hence CEA levels above 35 appear to be virtually diagnostic of the presence of cancer.
Tumor size as a prognostic indicator in colon cancer (CCa) patients undergoing sentinel lymph node mapping (SLNM) versus conventional surgery (CS) in National Cancer Data Base (NCDB).
Authors: Shaik Mohammed , Saha Sukamal , Saha Supriya Kumar , Johnston Gregory , Korant Alpesh K. , Wiese David , Dhar Vikrom K. , Eilander David , Arora Madan L. , Singh Trivor 
Published: February 2017

411 Background: Unlike other solid tumors, tumor size (TS) is not included in TNM staging for CCa. We correlated TS with TNM staging and 5-year overall survival (5yrOS) for patients (pts) who underwent SLNM vs CS in NCDB. Methods: A retrospectively review of 312 CCa pts undergoing SLNM compared to 298,021 CCa pts from NCDB undergoing CS between 1996 and 2010 was done. The maximum diameter of the primary tumor as TS, T and Nodal status were reviewed. Pts in each group was subdivided into 4 groups: (<2cm; 2-4cm; 4-6cm; >6cm). Data were analyzed using Spearman’s rho correlation and Kaplan-Meier for 5yrOS. Hazard ratios (HR) were calculated using a Cox model adjusting for age, sex, grade, T, N-status, and TNM stage. Results: Pts with TS <2 cm were mainly T1&T2 (80.7%, 74.8%), whereas for tumors >6cm, majority of pts were T3&T4 (93.2%, 88.8%). T1&T2 percentage consistently decreased as TS increased and T3&T4 percentage consistently increased with TS (Table). Nodal positivity according to tumor size for SLNM were 17%, 49%, 56%, 46% and for CS were 18%, 38%, 48%, 51%, respectively. In both groups, nodal positivity increased as TS increased. The overall nodal positivity in both groups was 46% and 42%. For SLNM and CS, overall survival decreased as TS increased. Overall SLNM pts had better OS when compared to CS pts (65%, 54%). Conclusions: Nodal +vity and overall survival where slightly better in SLMN pts. Vs CS pts. TS had +ve correlation with T staging and N status in 5 yr OS. Hence, TS may be considered a prognostic factor in CCa pts. [Table: see text]
The relationship between the local inflammatory response and postoperative infective complications following resection for colorectal cancer.
Authors: Ramanathan Michelle Leana , Roxburgh Campbell S. D. , Horgan Paul G. , Mcmillan Donald C. 
Published: February 2017

413 Background: In patients with colorectal cancer, the presence of both systemic and/ or local inflammatory responses are predictors of survival independent of tumour stage. The relationship between a raised perioperative systemic inflammatory response and the development of postoperative infective complications is also well established. The aim of the present study was to examine the relationship between the local inflammatory response and the development of postoperative infective complications, in patients undergoing resection for colorectal cancer. Methods: Patients with histologically proven colorectal cancer who, on the basis of laparotomy findings and preoperative abdominal computed tomography, were considered to have undergone potentially curative resection were included in the study (n = 310). Patient characteristics and postoperative complications within 30 days were recorded in a prospective surgical database. Local inflammation was analysed using Klintrup-Makinen criteria and Jass scoring on routine hematoxylin and eosin slides. Results: The majority of patients were 65 or older (66%), male (57%), had colonic tumours (68%) and node negative disease (60%). Most patients underwent elective resection (87%) and were from a deprived area (55%). During follow up 109 (35%) patients developed a postoperative complication; 88 (81%) of which had infective complications. There were no significant associations between local inflammation, as evidenced by Klintrup-Makinen criteria and Jass score, and all infective complications (p = 0.929, p = 0.317), surgical site infections (p = 0.956, p = 0.115), or anastomotic leak (p = 0.771, p = 0.157). Conclusions: The results of the present study show that there is no significant relationship between the degree of local inflammation, as evidenced by Klintrup-Makinen criteria and Jass score, and the development of postoperative infective complications following potentially curative resection for colorectal cancer.
Response to the first-line FOLFOX plus bevacizumab (BEV) therapy to predict responses to the subsequent therapies and survival in the BEV beyond progression (BBP) strategy for metastatic colorectal cancer: A retrospective analysis of CCOG-0801 study.
Authors: Nakayama Goro , Uehara Keisuke , Hayashi Naomi , Tanaka Chie , Kobayashi Daisuke , Kanda Mitsuro , Yamada Suguru , Fujii Tsutomu , Sugimoto Hiroyuki , Koike Masahiko , Nomoto Shuji , Fujiwara Michitaka , Ando Yuichi , Kodera Yasuhiro 
Published: February 2017

428 Background: The aim of this study was to evaluate the association of early tumor response to the first-line bevacizumab (BEV) combination therapy with efficacy of the subsequent therapies and survival during the BEV beyond progression (BBP) strategy for metastatic colorectal cancer (mCRC) patients. Methods: We analyzed a pooled data set from the previous phase II studies of mCRC, testing BBP strategy with the first-line mFOLFOX plus BEV (N=47) and the second-line FOLFIRI plus BEV (N=31). Patients were classified into either responders (R group, n=29) with tumor shrinkage (complete response [CR] + partial response [PR]), sub-responders (SR group, n=11) with stable disease (SD) and non-responders (NR group, n=5) with disease progression (PD) at the point of initial three months of the first-line therapy. The tumor response and PFS in the subsequent therapies and OS were evaluated. Results: In the first-line FOLFOX+BEV therapy, further tumor shrinkage was not achieved after the initial three months. PFS was 15.0 months for the R group, 8.9 months for the SR group and 2.9 months for the NR group, respectively, and there was statistical significance favoring the R group (p=0.001). In the second-line FOLFIRI+BEV, RR and DCR were 39 and 78% in the R group, 14 and 57% in the SR group, and 0 and 0% in the NR group, respectively. No additional response to the first-line therapy was observed in all groups, except for only one patient in the SR group. PFS was 8.8 months for the R group, 6.0 months for SR group and 1.4 months for NR group, respectively, and the R group was significant predictor for prolonged PFS in the second-line setting. OS were 30.8 months for the R group, 24.7 months for the SR group, and 11.1 months for the NR group, respectively. Early disease control (R+SR) was significant predictor for OS (hazard ratio [HR]: 8.48, p<0.01) in multivariate analysis. Conclusions: These findings indicate that the tumor response within initial three months of first-line BEV combination chemotherapy could predict efficacies of subsequent treatments and OS in the BBP strategy for mCRC patients. Clinical trial information: UMIN000006818.
Disparities in stage at presentation and treatment of colorectal cancer among Hispanic and non-Hispanic white patients.
Authors: Rodriguez Rodrigo , Gonzalez Melissa , Fahy Bridget N. , Kinney Anita , Rajput Ashwani 
Published: February 2017

433 Background: Although incidence rates for colorectal cancer (CRC) for Hispanics are similar to non-Hispanic whites (NHW) in New Mexico, the cause-specific mortality is higher among the Hispanic population. Hispanics have also been shown to be less likely to be current with colorectal cancer screening guidelines as compared to NHW. The purpose of this study was to determine if there was a difference between Hispanics and NHW in stage at presentation and if the care provided was concordant with NCCN guidelines at our NCI designated cancer center. Methods: A prospective data base of all patients who presented with colorectal cancer between June 2009 and July 2013 was queried. A total of 197 patients were identified. Data was extracted that included: demographics, stage of CRC at first diagnosis, treatments given, and pathology results. Frequencies of stage at presentation and NCCN guideline concordance (meeting the 12 lymph node metric, receipt of adjuvant therapy for stage III disease and radiation therapy for locally advanced rectal cancer) were recorded. Results: The Table shows the results. There were 107 (55%) males. There was not a statistical difference in the stage of presentation for Hispanics and NHW for patients with colon cancer. Hispanic patients with rectal cancer, however, presented with more advanced stage of disease as compared to NHW (p<0.05). There was no statistically significant difference in concordance with NCCN guidelines for the three metrics analyzed. Conclusions: Hispanics and NHW with colon cancer presented with similar stage of disease and were concordant with NCCN guideline metrics. Hispanics with rectal cancer, however, presented at a more advanced stage of disease as compare to NHW patients. The reason for this disparity remains to be elucidated. Future studies to include outreach, education, screening and molecular profiling of these disparate populations are planned. [Table: see text]
Prognostic and predictive blood-based biomarkers of overall survival (OS) in patients (pts) with advanced colorectal cancer (CRC) treated with cetuximab (C): Results from CALGB 80203 (Alliance).
Authors: Hatch Ace J. , Pang Herbert , Starr Mark D. , Brady John C. , Jia Jingquan , Niedzwiecki Donna , Venook Alan Paul , Cushman Stephanie M. , Hurwitz Herbert , Nixon Andrew B. 
Published: February 2017

448 Background: Previously, we identified potential predictive biomarkers of C sensitivity related to EGFR signaling from archived tumor tissue from CALGB 80203. Due to the fact that blood-based markers are more convenient and can be monitored over the course of treatment, baseline plasma samples were also collected and five (EGF, HB-EGF, sEGFR, sHER2, sHER3) of the 14 markers previously analyzed in archived tumor were evaluated in plasma. Methods: CALGB 80203 was a randomized (1:1) phase II trial of 238 pts with locally advanced or metastatic CRC comparing FOLFOX or FOLFIRI (chemo) vs. chemo combined with C. Baseline EDTA plasma samples from 154 pts were analyzed for the 5 candidate markers. The levels of each analyte were correlated with the primary endpoint of OS using univariate Cox proportional hazards models. Potential predictive markers were identified using a treatment by marker interaction term in the Cox model and the markers with significant p-values are reported. Hazard ratios between treatment groups are reported for low or high marker levels dichotomized at the median. Results: Univariate analyses indicated that plasma levels of EGF and sHER3 were negative prognostic markers (p<0.05) that correlated with OS for the overall pt population. Across all pts (KRAS mutant and wild-type), sHER3 was identified as a potential predictive biomarker for C. Pts with higher sHER3 levels had significant OS benefit from C treatment (interaction p=0.03; HR=0.57, 95% CI 0.36-0.92). Low levels of EGF predicted for OS benefit from C in KRAS WT tumors (interaction p<0.01; HR=0.39, 95% CI 0.18-0.87) and lack of benefit in the KRAS mutant pts (interaction p=0.03; HR=3.03, 95% CI 1.13-8.16), but were not predictive for C across all pts combined. Conclusions: Blood-based profiling of EGFR axis members identified sHER3 and EGF as candidate predictors for benefit from C. These data are consistent with our findings using mRNA expression from archived tumor samples and suggest a role for receptor shedding in HER3 biology. If further validated, these markers may help guide the development and use of anti-EGFR therapies and combination regimens.