Abstract

BackgroundStudies over the past 10 years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer (mCRC). Factors influencing SMM changes over time are, however, poorly studied. We analyzed the impact of SMM on overall survival and chemotherapy toxicities in mCRC patients treated with first-line chemotherapy. Changes in weight and body composition were evaluated during follow-up.MethodsPatients enrolled in the randomized phase II ACCORD trial comparing two chemotherapy regimens were screened. Body composition parameters (SMM, adipose tissue) were assessed prospectively with computed tomography (CT) imaging, and toxicities were recorded. Mixed models were used to assess weight and BC changes during 4 months of treatment follow-up.ResultsAmong 145 patients included in ACCORD, 76 had available baseline CT scans and were included in the current study. Mean age was 60.6 ± 10.0 years, 50% were women, 82% had colon cancer, and 62% had two or more metastatic sites. At baseline, 49% had lost at least 5% of their initial weight, including 26% who had lost more than 10%; 53% had SMM depletion. In this homogenous cohort, there were no statistically significant associations between SMM depletion and overall survival, progression-free survival or chemotherapy toxicity. There were no decreases in weight or SMM during follow-up. Weight and SMM changes were not influenced by diarrhea either grade 3–4 or any grade (reported in 74% of patients). For patients with weight loss ≥10% at baseline, SMM increased significantly after 4 months of follow-up and after disease stabilization following chemotherapy (P = 0.008).ConclusionsIn a homogenous mCRC cohort, SMM depletion was not associated with survival or chemotherapy toxicity. Despite most patient experiencing diarrhea, no changes in weight or SMM were found during 4 months of follow-up. However, hypotheses deriving from our exploratory study have to be tested in further larger sample size studies.Trial registrationClinicaltrials.gov NCT00423696 (2011).

Highlights

  • Studies over the past 10 years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer

  • In the past 10 years, studies have strongly suggested that skeletal muscle mass (SMM) depletion is associated with poorer survival outcomes independent of weight loss (WL) [6]

  • The additional analyses of clinical data and interpretation of body composition from computed tomography (CT) images in the current study were approved by the Gustave Roussy independent ethics committees

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Summary

Introduction

Studies over the past 10 years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer (mCRC). In the past 10 years, studies have strongly suggested that skeletal muscle mass (SMM) depletion is associated with poorer survival outcomes independent of weight loss (WL) [6]. In CRC, the deleterious effect of SMM depletion on overall survival (OS) has been described for stage I to III disease [7], for patients undergoing adjuvant chemotherapy [8], as well as for short-term postoperative outcomes [9,10,11,12]. SMM depletion has been associated with chemotherapy toxicity and discontinuation of chemotherapy treatments in many cancer types [13,14,15], and especially for CRC [8, 16,17,18]

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