Prognostic factors for severe diarrhea in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation with capecitabine: A single-center cohort study.

Abstract

e15176 Background: Chemoradiation with concomitant capecitabine (CRT) followed by total mesorectal excision is the standard of care for locally advanced rectal carcinoma (LARC). Grade ≥ 3 diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiotherapy. The aim of this study is to describe the risk factors of grade ≥ 3 diarrhea in patients with LARC during CRT. Methods: A single centre retrospective cohort study was conducted in our tertiary center. All patients with LARC treated with CRT from 2009 to 2015 were included. Patients with local recurrence who received CRT for the first time were also included. Univariate logistic regression analyses were used, followed by a multivariate analysis of the significant factors with backward selection at p < 0.05. Results: A total of 738 patients were included: 67% male, median age 64 years (range 17-88), 95% primary presentation. DPYD-testing was not performed upfront. In this cohort 69 patients (9%) developed ≥3 grade diarrhea. In the univariate analysis, factors significantly associated with ≥3 grade diarrhea were; female gender, age ≥65 years, body weight and decreased renal function (defined as MDRD GFR < 60 ml/min/1,73 m2). The following factors remained significantly associated with ≥3 grade diarrhea in the multivariate analysis; female gender (odds ratio (OR) 2.77, 95% confidence interval (CI) 1.54-4.99, p 0.001), age ≥65 years (OR 2.85, 95% CI 1.63-4.98, p < 0.001) and a lower bodyweight (OR 0.98, 95% CI 0.96-1.00, p 0.015). Conclusions: Female gender and age ≥65 years significantly increase the risk of grade ≥ 3 diarrhea caused by neoadjuvant CRT for LARC. So, older female patient must be closely watched during this treatment to intervene on time. The difference in toxicity between females and males might be explained by the pelvic anatomical differences between men and women. The found prognostic factors will be validated in a second cohort of patients with LARC treated with CRT. Besides, sarcopenia will be tested as a prognostic factor as well.