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Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy.

ABSTRACT: Postoperative chemotherapy is standard following preoperative chemoradiation therapy (CRT) and curative resection for clinically staged II/III rectal cancer. Recent trials have questioned whether postoperative chemotherapy improves overall survival. The objective of the study was to evaluate the comparative effectiveness of postoperative chemotherapy following CRT or radiation therapy (RT) with specific attention to the impact of age on postoperative chemotherapy effectiveness.Patients treated with CRT or RT then resection of pathologically staged 0-III rectal cancer diagnosed from 2004 to 2009 were identified from the Surveillance, Epidemiology and End Results program-Medicare database. Propensity score weighted Cox proportional hazards models and Kaplan Meier methods were used to compare the effectiveness of 1) postoperative 5-fluorouracil (5-FU) or capecitabine to no treatment and 2) postoperative oxaliplatin+5-FU/capecitabine to 5-FU/capecitabine alone on mortality. Results were stratified by age.We identified 1316 patients; 49% received postoperative chemotherapy, 341 (52%) included oxaliplatin. After weighting, postoperative 5-FU/capecitabine alone was associated with decreased mortality in patients aged 66-74 (adjusted hazard ratio (aHR)=0.46, 95% CI: 0.30, 0.72), corresponding to a 5-year risk difference of -0.23, (95% CI: -0.33, -0.12). No further mortality reduction from adding oxaliplatin to 5-FU/capecitabine was seen in patients aged 66-74 (aHR=1.57, 95% CI: 0.93, 2.65). No mortality reduction for 5-FU/capecitabine alone was observed among patients aged 75+ (aHR=1.11, 95% CI: 0.76, 1.63).Among patients <75years, postoperative 5-FU/capecitabine was associated with reduced mortality after preoperative CRT/RT and surgical resection; however, the addition of oxaliplatin was not associated with further mortality reduction. Decisions regarding postoperative chemotherapy after age 75 warrant consideration of individual patient risks and preferences, as benefits may be limited.

SUBMITTER: Lund JL

PROVIDER: S-EPMC4871747 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy.

Lund Jennifer L JL Sturmer Til T Sanoff Hanna K HK

Journal of geriatric oncology 20160223 3

<h4>Objective</h4>Postoperative chemotherapy is standard following preoperative chemoradiation therapy (CRT) and curative resection for clinically staged II/III rectal cancer. Recent trials have questioned whether postoperative chemotherapy improves overall survival. The objective of the study was to evaluate the comparative effectiveness of postoperative chemotherapy following CRT or radiation therapy (RT) with specific attention to the impact of age on postoperative chemotherapy effectiveness. ...[more]

PMID: 26926829

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Project description:The incorporation of chemoradiation prior to resection of the tumour has revolutionized the management of locally advanced rectal cancer. However, a large proportion of these patients are resistant to preoperative treatment schedule. We recently reported that c-Myc gene expression correlates negatively with this resistance in patients with rectal cancer. In this study, we carried out integrated analysis of miRNA and mRNA expression profiling in 45 pre-treatment rectal tumour. Further, expression of miRNAs and c-Myc, and their relationship with clinicopathological factors and patient survival was analysed. As a result, we found that 12 miRNAs were differentially expressed between responder and non-responder rectal cancer patients. Functional classification revealed an association between differentially expressed miRNAs and c-Myc. Subsequent quantitative real-time PCR results showed that both, miRNA-148 and miRNA-375 levels were significantly lower in responder compared to non-responder patients. Notably, the higher level of miRNA-375 was significantly negatively correlated with c-Myc. These results suggest that miRNA-375 and its targeted c-Myc play an important role as predictive biomarker of response to neoadjuvant treatment in patients with locally advanced rectal cancer, but still not suitable for prognosis. Pre-treatment biopsies of 22 patients with LARC were prospectively collected and freshly frozen according to an institutional board-approved protocol. Tumour response was assessed in surgical specimens by pathological examination based on the semi-quantitative tumour regression grading (TRG) system described by Mandard in 1994[36]: TRG1 and TRG2 scores were considered responders, whereas TRG3, TRG4, and TRG5 were classified as non-responders. The inclusion criteria were: histologically proven rectal tumour at a clinical stage UICC II-III (cT3-4/and or N positive), following endorectal ultrasound and/or MRI scan. Patients were excluded if they had the tumour located above 13 cm from the anal verge by rigid rectoscopy, synchronic colonic cancer assessed by colonoscopy, distant metastases by 18FDG PET-CT scan, and suspicion of hereditary colorectal cancer. All patients subsequently received a total dose of 50.4Gy of radiation (28 fractions of 1.8Gy) associated with capecitabine (oral form of 5-FU) with or without oxaliplatine, according to our Hospital Clinical Practice Guidelines. Standardized Surgery was performed, including total mesorectal excision, following an interval of 8-10 weeks after completion of CT/RT.

Dataset Information

Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy.

Publications

Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy.

Similar Datasets

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