bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsatellite high colorectal cancer: Does the underlying mechanism for instability matter?
Authors: Hyngstrom John Robert , Rodriguez-Bigas Miguel A. , Chang George J. , Taggart Melissa W. , Skibber John Michael , Feig Barry W. , You Y. Nancy 
Published: February 2017

575 Background: Microsatellite instability (MSI) testing in colorectal cancer (CRC) provides prognosis, predicts chemotherapy response, and guides diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MSI can be sporadic or hereditary, arising from somatic or germline mutations in DNA mismatch repair (MMR) genes respectively. The clinical implications of these distinct mechanisms are uncertain. Methods: Patients who underwent MSI testing for CRC between 2000 and 2011 were identified. MSI-high (MSH) CRCs were defined by: pathogenic mutation in MMR genes; >30% of markers with allelic shift in PCR-based MSI testing; or loss of expression in at least 1 MMR protein on immunohistochemistry. The subset with MLH1 gene promoter methylation, BRAF mutation, or EPCAM mutation was considered sporadic. Clinicopathologic features and disease-free survival (DFS) were examined in reference to microsatellite stable (MSS) CRCs. Results: MSH CRC’s, 92 germline and 49 sporadic, were compared with 105 MSS CRCs. Compared to MSS CRCs, both germline and sporadic MSH CRCs more commonly arose in the proximal colon (63% and 92%, vs. 30%; p<.001), exhibited mucinous/signet ring histology (40% and 47%, vs. 16%; p<.001) and lymphocytic infiltrate/Crohn’s like reaction (15% and 49%, vs. 8%; p<.001). Further comparison between germline vs. sporadic MSH CRCs revealed significant differences in median age (44 yrs. vs. 66; p<.001), proximal colon tumor location (63% vs. 91%; p<.001), AJCC stage (33% vs. 51% Stage III or IV; p<.025) and presence of lymphocytic/Crohn’s like reaction (49% vs. 15%, p<.001). Moreover, sporadic MSH CRCs more often had poor prognostic features including poor differentiation (51% vs. 28% in germline, p<.025) and lymphovascular invasion (57% vs. 34% in germline, p<.007). No difference was observed in stage-stratified DFS between germline vs sporadic MSH CRCs. Conclusions: Patients with sporadic MSH CRCs exhibit distinct clinicopathologic features compared to those with germline MSH tumors. Despite poor prognostic features, no apparent survival difference was observed. Further characterization of these distinct groups is warranted to explain the discordance between risk factors and outcomes.
Cetuximab (C225) in the first-line treatment of advanced colorectal cancer (CRC) patients (Pts) with K-ras wild-type (WT) tumors: Does the choice and schedule of fluoropyrimidine (Fp) matter?
Authors: Ku Geoffrey Yuyat , Haaland Benjamin , Lopes Gilberto de Lima 
Published: February 2017

576 Background: C225, a monoclonal antibody against the epidermal growth factor receptor, has been shown to inconsistently improve response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced CRC Pts with K-ras WT tumors. Methods: We performed a meta-analysis of four trials where K-ras WT Pts received a Fp (capecitabine (C) or bolus (b) or infusional (CI) 5-fluorouracil (5-FU)) and oxaliplatin (oxali) or irinotecan (CPT) ± C225 (CRYSTAL, OPUS, COIN and NORDIC VII trials) and one trial, where K-ras WT and mutant Pts received C225 with capecitabine (C) and oxali or CPT (AIO study). We sought to determine if the choice of Fp affects the response to C225. A mixed effects model similar to that of DerSimonian and Laird was fit by restricted maximum likelihood and used to obtain an overall estimate of the effect of C225 in the presence of CI 5-FU, an indirect estimate of the decrease in the effect of C225 in the presence of C/b5-FU relative to CI 5-FU, and an estimate of the study-to-study variability. Results: Only Pts treated with CI 5-FU based chemo derived benefit from C225. Relative to CI 5-FU, Pts treated with C or b5-FU based doublet chemo had a decrease in RR, PFS and OS. The choice of oxali or CPT did not affect responses to C225. Conclusions: The lack of benefit for C225 with C or b5-FU chemo is unexpected. A possible explanation is increased toxicity with C225, which led to dose reduction of C only in the C225-arm of the COIN study; however, increased toxicity was not seen in the NORDIC VII study. Pending further study, only CI 5-FU regimens should be used with C225. [Table: see text]
Evaluation of relapse-free survival in T3N0 colon cancer: The role of chemotherapy—A multicentric retrospective analysis.
Authors: Grande Roberta , Cosimelli Maurizio , Gemma Donatello , Ciancola Fabrizio , Corsi Domenico C. , Rossi Lorena , Sperduti Isabella , Fabbri Maria Agnese , Mancini Raffaello , Ruggeri Enzo , Zampa Germano , Bianchetti Sara , Gamucci Teresa 
Published: February 2017

578 Background: Use of adjuvant chemotherapy (AC) in stage II colon cancer (CC) is still under debate. Choice should be based on patients (pts) and disease characteristics. According to worldwide guidelines AC should be considered in high-risk (H) T3N0 pts. No data are available for better option in low-risk (L) pts. Aim of the study is to evaluate relapse-free survival (RFS) and disease-free survival (DFS) retrospectively in T3N0 CC pts related to treatment. Methods: RFS and DFS are evaluated with Kaplan Meier method. In order to find the optimal cut off for node number the receiver operating characteristics curve analysis and maximally selected rank statistics were performed. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15 respectively. Results: 1,000 pts with T3N0 CC were recruited. To date, data of 764 pts are available. Median age was 68 (29-93), M/F 42/344, grading 1/2/3 40/561/132; 303 L (40%), 356 H (46%), 105 unknown (14%); 121 (16%) pts showed symptoms (S) at diagnosis: 43 pts had perforation (P) or bowel obstruction (BO). Median sampled lymph nodes (LN) were 15 (1-76); 339 (44%) pts were treated with AC. Median follow up (fu) was 5 years (yr) (range 3-24). Survival analysis analysis was performed only for pts with a minimum fu of 3 yr and younger than 80 (79%). 5 yr RFS was 79% and 5 yr DFS was 77%. At multivariate analysis S, LN and AC were prognostic factors for RFS. AC is prognostic factor for all endpoints (Table). In L group 5 yr RFS was 88% in treated pts and 71% in non-treated pts (p 0.004); in H group was respectively 84% and 70% (p 0.002). Conclusions: Preliminary data confirmed the role of known prognostic factors and suggest the relevance of AC also in L stage II T3N0 CC pts. However, the highest risk in L subgroup should be identified to be submitted to AC. Data collection is ongoing. [Table: see text]
Are we getting better at treating patients with rectal cancer? A 15-year trend analysis.
Authors: Guller Ulrich , Koeberle Dieter , Warschkow Rene , Schmied Bruno , Cerny Thomas , Tarantino Ignazio 
Published: February 2017

589 Background: The objective of this trend analysis was to assess whether clinical outcomes following rectal cancer resection have improved over a 15-year time period. Methods: The present study is based on the colorectal database of the authors` hospital, one of the largest tertiary care centers of Switzerland. All patients undergoing a rectal cancer resection for stage I - IV disease were consecutively included between 1991 and 2005. The 15-year time period was subdivided into five 3-year periods, among which different outcomes were compared. All tests were two-sided, the level of statistical significance was set at 0.05. Results: Overall, 682 consecutive patients undergoing a rectal cancer resection for stage I - IV disease were included. Mean age was 65 years (range: 24 to 93 years), 62.1% of patients were male, median ASA physical status was 2 (range 1 – 4). Among the various time periods, there were no significant differences regarding patients` demographics as well as tumor stage. All following outcomes significantly decreased over time: operating room time (max. 217minutes to 164 minutes, P-trend: <0.001), rate of abdomino-perineal resections (from 20.5% to 7.6%; P-trend < 0.001), rate of R1/2 resections (from 16.9% to 8.6%; P-trend: 0.008), rate of intraoperative complications (from 16.9% to 4.9%; P-trend: 0.018), rate of general postoperative complications (from 59% to 35.1%; P-trend <0.001), and rate of local recurrence (8.4% to 4.9%; P-trend:0.033). 5-year overall survival did not significantly change over time, neither in the overall patient cohort (P-trend: 0.476), nor in the subsets of stage I-III (P-trend: 0.675) and stage IV patients (P-trend: 0.486). Conclusions: This first study in the literature based on a large cohort of consecutive stage I – IV rectal cancer patients provides compelling evidence that that operating room time as well as rates of abdomino-perineal resections, R1/2 resections, intra- and postoperative complications, as well as rates of local recurrence have significantly decreased from 1991 – 2005. However, there was no significant improvement of overall survival, neither in the overall cohort nor in the subsets of stage I-III versus stage IV rectal cancer patients.
Twenty years of chemotherapy for colorectal cancer (CRC): Progress made, insights gleaned.
Authors: Jawed Irfan , Wilkerson Julia , Duffy Austin G. , Fojo Antonio Tito 
Published: February 2017

596 Background: The past 20 years have seen progress in CRC therapy with more effective agents and better medical, surgical and supportive care. Methods: We conducted a systematic review of 101 phase III and large phase II trials in CRC to quantify benefit over time with first-line and subsequent therapies. Outcomes examined in the experimental (EA) and control arms (CA) included progression-free survival (PFS), overall response rate (ORR), stable disease (SD), overall survival (OS) and post-treatment survival (PTS). Data were analyzed according to dates of publication and median enrollment. Results: Significant outcomes are reported; most had R2 values > 0.6. OS of EA improved 0.83 mos/yr. Importantly the OS of CA improved 0.58 mos/yr likely reflecting use of experimental therapies in CA in subsequent studies and improvement in CRC care over time as suggested by: (1) modest improvements of PFS: 0.33 [EA] and 0.26 [CA] mos/yr; (2) PTS gains of 0.48 [EA] and 0.29 [CA] mos/yr, accounting for majority of OS gains; and (3) lack of OS improvement in 14 second/subsequent line trials. Using logistic regression to examine all drugs as class predictors of increasing OS, oxaliplatin [OX], bevacizumab [BEV], and irinotecan [IRI] were significant in the EA, but only OX and BEV were significant in the CA. Capecitabine [CAP] and cetuximab/panitumumab [CET/PAN] were not significant in EA or CA, with CAP odds ratio towards null and CET/PAN odds ratio away from null. The lack of IRI effect in CA concurs with observation that only IRI regimens had worse OS in CA compared with EA. The CET/PAN results likely reflect lack of efficacy/harm in patients with WT KRAS tumors. As expected PFS and PTS correlate highly with OS, but importantly ORR had very high correlations with both PFS and OS. SD emerged as an “adverse” outcome, OS decreasing as SD rates increase. Conclusions: OS of CRC patients has improved gradually over past two decades, with gains from chemotherapy but also other factors, such as lead-time bias, more loco-regional approaches and improved supportive care. IRI performed better in EA than in CA. CET/PAN had negative effects in the entire population. In CRC, ORR correlates highly with OS, while SD portends a poor outcome.
Factors associated with use of chemoradiation for rectal cancer.
Authors: Charlton Mary E. , Lin Chi , Pendergast Jane F , Chrischilles Elizabeth A. , Wallace Robert B 
Published: February 2017

607 Background: Adjuvant or neoadjuvant chemotherapy (chemo) and radiation therapy (RT) have been the standard of care for virtually all patients with stages II/III rectal cancer for 20 years. However, recent analyses of the SEER database have demonstrated variation in treatment. Leveraging the clinical characteristics and patient beliefs available in the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) cohort, we determined the proportion and associated characteristics of those who received chemo and RT. Methods: We identified CanCORS patients with stage II/III rectal cancer with primary site resection, and used data from patient surveys and abstracted medical records to construct variables (age, gender, marital status, race, education, income, insurance status, stage, comorbidity, patient treatment beliefs, staging procedures, tumor location/size, types of providers seen). Results: Of the 310 eligible patients, 14% received neither chemo nor RT, 13% received chemo or RT, and 73% received both. Receipt of chemo and RT was associated with younger age, stage III, rectosigmoid junction (vs. rectum NOS) tumor, receipt of staging PET, and patient beliefs that chemo/RT would help them live longer, cure their cancer and help with symptoms. In a logistic model, age (<55 vs >65; OR=2.2, 95% CI: 1.31, 3.46), stage (III vs. II; OR=1.52, 95% CI: 1.06, 2.17), PET (OR=2.41, 95% CI: 1.15, 5.03) and rectosigmoid junction tumor (OR=1.59, 95% CI: 1.10, 2.29) were associated with receipt of chemo; similarly, age and rectosigmoid junction tumor were associated with RT. Of those who did not receive chemo or RT, 35% reported they did not think chemo/RT would help, 65% reported their doctor said chemo/RT would not help and 18% were worried about side effects; 65% reported they never saw a medical or radiation oncologist and 26% reported that no doctor ever discussed the possibility of chemo or RT. Conclusions: A significant proportion of patients with stage II/III rectal cancer did not receive chemo and RT, and a number of those reported that no doctor ever discussed the possibility of chemo or RT with them. While deviation from guidelines may be warranted and/or patient driven, further analyses should determine reasons for lack of recommended treatments.
Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.
Authors: Suenaga Mitsukuni , Matsusaka Satoshi , Mizunuma Nobuyuki , Shinozaki Eiji , Ogura Mariko , Ozaka Masato , Takagi Koichi , Yamaguchi Toshiharu , Hatake Kiyohiko 
Published: February 2017

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.
Progression-free survival (PFS) with maintenance treatment with bevacizumab (B) in patients with responding mCRC after first-line chemotherapy (CT) plus B.
Authors: Fabbri Maria Agnese , Nelli Fabrizio , Moscetti Luca , Cortesi Enrico , Gamucci Teresa , Sperduti Isabella , Franco Daniela , Pavese Ida , Grande Roberta , Alesini Daniele , Ruggeri Enzo 
Published: February 2017

612 Background: Maintenance treatment with B is considered an option for mCRC pts in responding pts after a first line CT + B, but few data are available on its real benefit on PFS. Methods: We collected data from a cohort of mCRC pts consecutively treated in five oncologic centers of Lazio. One-hundred-ninety-nine mCRC pts treated with first line CT + B achieving a response [partial (PR) or complete (CR)] or a stable disease (SD) were considered eligible, 117 pts had received B maintenance (BM) whereas 82 did not (noBM). The two groups were homogeneous for main characteristics. First-line therapy in the BM vs noBM group included FOLFIRI regimen (96 vs 59 pts), FOLFOX (18 vs 22 pts) and FUFA (3 vs 1 pts). K-ras status was analyzed in 115 pts with an higher percentage of wild-type (wt) in the BM group (65 vs 50 pts, p= 0.04). A CR or PR have been achieved in 65% of pts in the BM group and 61% of noBM group, while a SD was observed in 35% and 39% of pts respectively for the BM and noBM group. The median number of BM cycles administered was 7 (range 3-25). Effectiveness measures included the PFS duration. A multivariate Cox proportional hazard model was developed using stepwise regression (forward selection) Results: At a median follow-up of 18 months (1-109), the median PFS was 13 months (C.I.95%: 11-15) vs 8 months (C.I.95%: 7-10; p<0.0001, and the 1-year PFS 53% vs 28% for BM and noBM respectively. Pts with CR/PR had a mPFS of 15 months (CI 95% 12-19) vs 10 months (CI 95% 10-12) p=0.004 and a 1-year PFS of 62.6% vs 33.7% for the BM vs noBM group respectively. No difference in the 1-year PFS was observed in pts showing SD to chemotherapy and bevacizumab. The mPFS in these patients was 12 (CI 95% 10-13) vs 8 months (CI 95% 7-10, p=0.11) for the BM and noBM group respectively. The multivariate analysis did not show any difference in PFS comparing age, sex, number and site of metastasis, ECOG PS and k ras status. A significant difference in PFS was observed for response to first-line CT (CR/PR vs SD, p=0.002) and for BM vs noBM (p=0.003). Conclusions: The maintenance strategy with B shows a longer PFS in pts responding to the first line chemotherapy + B whereas for pts who achieving an SD no difference was observed.
Survival investigation in patients with colorectal liver metastasis: A single-institution analysis.
Authors: Xu Jianmin , Zhu Dexiang , Ren Li , Wei Ye 
Published: February 2017

617 Background: To investigate survival in patients with colorectal liver metastasis (CRLM) and identify risk factors associated with survival. Methods: Clinical, pathologic, treatment and complete follow-up data were retrospectively collected from 1613 consecutive patients with CRLM in Zhongshan Hospital between 2000 and 2010. The prognostic value of different factors was studied through univariate and multivariate analyses. Results: The median survival was 22.0 mo and 5-yr survival rate was 16%. Survival of synchronous liver metastases (SLM) (21.2 mo and 16%) was lower than that of metachronous liver metastases (MLM) (30.1 mo and 23%, p<0.01). Survival after resection of liver metastases was 49.8 mo and 37%, higher than that after chemotherapy (22.2 mo and 0%), that after intervention(19.0 mo and 11%), that after chemotherapy combined with intervention(22.8 mo and 10%)and that after local regional treatment (28.5 mo and 0%). Expansion of the indications for liver resection (38.0 vs 48.0 mo, 32% vs 40%), simultaneous or staged resection of primary colorectal tumor and liver metastases (47.0 vs 44.0 mo, 33% vs 35%) and preoperative neoadjuvant therapy (44.0 vs 48.0 mo, 38% vs 36%) had no significant effect on survival. 64 initially irresectable patients could undergo surgery after convertible therapy, with the median survival 36.9 mo and 5-yr survival 30%, better than that of unresectable patients (18.2 mo and 8%). Five factors were found to be significant and independent predictors of poor survival by multivariate analysis: SLM, poorly differentiated primary, number of liver metastases >= 4, largest liver metastases >= 5 cm, and no surgical treatment of liver metastases. Giving one point to each above factor, the population was divided into six groups with 5-yr survival rates: 0 (64%), 1 (44%), 2 (29%), 3 (4%), 4 (4%) and 5 (1%) (p<0.01). Conclusions: Survival of SLM was lower than that of MLM. Resection of liver metastases provides good long-term survival benifit for patients with resectable and initially irresectable liver metastases. Expansion of the indications for liver resection is acceptable. Long-term survival outcome can be predicted from a risk factor scoring system.
Cetuximab in first-line treatment of metastatic colorectal cancer in a real-life setting: Preliminary results of the EREBUS cohort.
Authors: Smith Denis , Rouyer Magali , Mitry Emmanuel , Monnereau Alain , Sa Cunha Antonio , Bignon Emmanuelle , Le Monies Alise , Jove Jeremy , Noize P. , Moore Nicholas , Fourrier-Réglat Annie 
Published: February 2017

621 Background: Cetuximab (CTX) has demonstrated to improve survival outcomes in metastatic colorectal cancer (mCRC), but little data for real-life use is available. Methods: EREBUS is a French multicentre (n=92) hospital-based cohort. Patients initiating CTX in 2009 and 2010 were identified retrospectively from registries of nominative drug dispensations. Those with wild-type KRAS gene receiving 1st-line treatment for mCRC were followed-up for 12 months. Data were collected from patient medical records and response based on physician assessments (CT-Scan). Presented here are preliminary results of the EREBUS cohort about administration regimen and according response rates for patients included in 2009. Results: Of the 190 patients included in the cohort, data has been collected for 160 (84.2%): median age at baseline 65.5 years, 70.6% male. Regarding cancer characteristics, 79.4% of patients had a colon cancer and 53.8% a primary tumor resection. Metastatic sites were liver in 73.1% of patients, peritoneum in 29.4%, lymph nodes in 26.3%, and lung in 25.6%. For patients for which the ECOG status was available (54.4%): 79.3% have an ECOG score between 0 and 1, 20.7% ≥2. Half the patients (48.8%) had only one metastatic site. CTX was given every three weeks to 2 patients (1.3%), every two weeks to 113 of patients (70.6%), and weekly to 45 (28.1%). For those receiving CTX every two weeks: 64.9% had irinotecan-based regimens (vs. 45.5% of those receiving CTX weekly, p=0.03), 31.5% had oxaliplatin-based regimens (vs. 47.7%, p=0.06), median duration of CTX use was 3.8 months (vs. 5.3 months, p=0.69) and that of 1st-line therapy 6.3 months (vs. 7.5 months, p=0.97), 69.0% discontinued 1st-line treatment (vs. 82.2%, p=0.09) – mainly for progression (71.8 vs. 75.7%, p=0.66) or toxicity (20.5 vs. 10.8%, p=0.20). Overall response evaluated for 100 patients receiving CTX every two weeks out of 113 was 46.0% (vs. 52.6%, p=0.49, evaluated for 38 receiving CTX weekly). Conclusions: CTX administration every two weeks was the most frequent regimen. In this preliminary analysis, patients receiving weekly or every two weeks regimens had similar duration of treatment and response rate.