Dataset Information

Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology).

ABSTRACT: BACKGROUND:We tested the association of colon tumour sidedness with prognosis and with molecular subtypes recently shown to be predictive of oxaliplatin benefit in stage III colon cancer. METHODS:NSABP/NRG C-07 trial (N=1603) was used to determine association of tumour sidedness with molecular subtypes and recurrence-free survival (RFS) and overall survival (OS). RESULTS:Sidedness was associated with molecular subtypes except stem-like/CMS4 subtype. Patients with stage III, left-sided tumours showed superior OS but not RFS. Sidedness was not associated with prediction of oxaliplatin benefit when combined with 5-Fu+LV. However, greater benefit from oxaliplatin was observed in a small subset of stage III patients with left-sided, enterocyte-subtype tumours (interaction HR=0.17, P=0.01). CONCLUSIONS:Sidedness was associated with molecular subtypes and was predictive of OS in stage III colon cancer but was not predictive of RFS or oxaliplatin benefit in C-07. Molecular subtypes may provide more predictive value for oxaliplatin benefit than tumour sidedness.

SUBMITTER: Kim SR

PROVIDER: S-EPMC5846062 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology).

Kim S Rim SR Song Nan N Yothers Greg G Gavin Patrick G PG Allegra Carmen J CJ Paik Soonmyung S Pogue-Geile Katherine L KL

British journal of cancer 20171214 5

<h4>Background</h4>We tested the association of colon tumour sidedness with prognosis and with molecular subtypes recently shown to be predictive of oxaliplatin benefit in stage III colon cancer.<h4>Methods</h4>NSABP/NRG C-07 trial (N=1603) was used to determine association of tumour sidedness with molecular subtypes and recurrence-free survival (RFS) and overall survival (OS).<h4>Results</h4>Sidedness was associated with molecular subtypes except stem-like/CMS4 subtype. Patients with stage III, ...[more]

PMID: 29241223

Similar Datasets

Project description:ImportanceOxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit.ObjectiveTo test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy.Design, setting, and participantsParticipants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked-down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods.InterventionsFluorouracil plus leucovorin with or without oxaliplatin.Main outcomes and measuresPercent recurrence-free survival.ResultsAmong 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C-07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09-0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22-1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73-1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly identified patients with poor prognosis (stemlike, CCS-3, and CMS-4) in both stage II and III.Conclusions and relevancePatients with stemlike tumors may be appropriate for clinical trials testing experimental therapies because stemlike tumors were robustly identified and associated with a poor prognosis regardless of stage or chemotherapy regimen. The clinical utility of using subtyping for the identification of patients for treatment with oxaliplatin requires validation in independent clinical trial cohorts.Trial registrationclinicaltrials.gov Identifier: NCT00004931.

Project description:BackgroundThere has been limited evaluation of health-related quality of life (HRQOL) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. HRQOL outcomes in the National Surgical Adjuvant Breast and Bowel Project R-04 trial are examined in this article.MethodsBetween 2004 and 2010, R-04 patients were invited to enroll in the HRQOL substudy, with questionnaires administered before randomization, after completion of chemoradiotherapy, and 1-year after surgery. HRQOL measures included: Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C); Short Form-36v.2 Vitality scale; a treatment-specific symptom scale; and the FACT neurotoxicity scale. A 5-year postsurgery assessment was added to the protocol in 2012. Mixed-effects models examined neoadjuvant therapy treatment effects in the 1-year sample and models that explored associations of host factors and treatment impact on 5-year HRQOL.ResultsA total of 1373 patients completed baseline HRQOL and at least one additional assessment. The average age was 58 years (range, 23-85 years), male (68%), and 59% Stage II. There were no statistically significant differences in HRQOL outcomes by treatment arm, but HRQOL worsened from baseline to postneoadjuvant chemoradiotherapy, with statistically significant effect sizes changes ranging from 0.6 (Vitality) to 0.9 (FACT-C Trial Outcome Index). Neurotoxicity was greater in the oxaliplatin-treated groups. Obese/overweight patients had statistically significantly worse FACT-C Trial Outcome Index scores than did underweight/normal weight groups. At 5 years, younger patients and those with normal baseline weight had statistically significantly better physical function scores and older patients had better mental health outcomes.ConclusionsHRQOL did not differ across the four R-04 treatment arms; however, host factors explained significant variation in posttreatment HRQOL.Clinicaltrialsgov: NCT00058474 (https://ClinicalTrials.gov/ct2/show/NCT00058474).Lay summaryThis article reports on the health-related quality of life (HRQOL) outcomes of patients treated with four different chemotherapy regimens combined with radiation in rectal cancer patients before definitive surgical treatment. There were no significant differences in HRQOL by treatment regimen, but all patients experienced decreased vitality (energy) and physical functioning. By 1 year after treatment, most patients had returned to pretreatment vitality and physical functioning, with the exception of increased neurotoxicity. In a subsample of patients assessed at 5 years after surgery, physical function was better in those who at pretreatment were younger, normal weight, and had better performance status. Mental function was better in those who at pretreatment were older and had better performance status.

Dataset Information

Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology).

Publications

Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets