Skeletal Muscle Loss During Definitive Chemoradiotherapy is Negatively Associated with Outcomes in Locally Advanced Cervical Cancer

Abstract

Concurrent chemoradiation (CCRT) is the mainstay of treatment for patients with locally advanced cervical cancer (LACC). Emerging reports suggest that sarcopenia might be associated with poor prognosis in many cancers; however, the effect of sarcopenia and skeletal muscle loss during CCRT for LACC remains unknown. We hypothesized that skeletal muscle loss during CCRT could impact outcomes. The aim of this study was to assess the effects of sarcopenia and skeletal muscle changes on the outcomes of patients with LACC. We analyzed the pre- and post-CCRT computed tomography (CT) images of 245 patients with LACC who were treated between 2004 and 2015. The post-CCRT CT images were acquired within 3 months of CCRT. The third lumbar vertebrae (L3) was chosen as a standard landmark, and two consecutive CT images were used to measure the cross-sectional area of the skeletal muscle. Skeletal muscle was identified and quantified by the use of Hounsfield unit thresholds (–29 to +150). The skeletal muscle index (SMI) was calculated as the area of total L3 skeletal muscle (cm2) divided by the square of the height (m2). Sarcopenia was defined as SMI <38.5 cm2/m2. The SMI change was calculated as follows: [(post-CCRT SMI - pre-CCRT SMI)/pre-CCRT SMI] × 100. Patients with an SMI loss or gain of more than 10% were classified as having experienced ‘SMI loss’ or ‘SMI gain,’ respectively. The Cox’s proportional hazards model was used to test for the combined effects of prognostic factors. Survival probabilities were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). The median follow-up was 62.7 (range, 7.3-152.3) months. Among the 245 patients, 108 (44%) had pre-CCRT sarcopenia. The median interval between pre- and post-CCRT CT scans was 4.8 (range, 3.5-5.9) months. The number of patients who were diagnosed with SMI loss, stable SMI, and SMI gain were 51 (21.8%), 144 (58.5%), and 50 (20.4%), respectively. The survival outcomes were similar in the pre-CCRT sarcopenia and non-sarcopenia groups (5-year overall survival [OS]: 82.5% vs. 83.0%, p = 0.78; 5-year progression-free survival [PFS]: 72.2% vs. 78.8%, p = 0.25). The 5-year OS for the SMI loss, stable SMI, and SMI gain groups was 44.8%, 91.7%, and 95.8%, respectively (p < 0.001), and the 5-year PFS was 38.4%, 84.7 %, and 89.3%, respectively (p < 0.001). On multivariable analysis adjusted for FIGO stage, lymph node status, histology, and treatment, the SMI change, as a continuous variable (HR, 0.77; 95% CI, 0.71–0.83; p < 0.001), and SMI loss (HR, 6.22; 95% CI, 3.12–12.43; p < 0.001) were significant prognostic factors for OS. Pre-CCRT sarcopenia was not an independent prognostic factor for OS (p = 0.78). Skeletal muscle loss during CCRT was a poor prognostic factor for survival in patients with LACC. Our results demonstrate that the importance of body composition in patients with cancer, highlighting the need for specific interventions to improve unfavorable body compositions for potentially improving outcomes.