Loss of muscle mass during cancer therapy is associated with poor oncologic outcomes in epithelial ovarian cancer

Abstract

<h3>Objectives:</h3> Sarcopenia, a loss of muscle mass and function, is a risk factor for decreased survival in advanced epithelial ovarian cancer (EOC). Little is known about the effect of primary treatment for EOC on sarcopenia and how this relates to patient outcomes. Our aim was to determine the change in sarcopenia measures over the course of primary EOC treatment and if changes are associated with overall survival. <h3>Methods:</h3> We utilized an institutional EOC surgical database to identify patients diagnosed with stage IIIC or IV EOC who received primary debulking surgery (PDS) and adjuvant chemotherapy at our institution. Patients were included if they had pre and post-treatment computerized tomography (CT) scans available. Patient CT scans were analyzed for body composition, including skeletal muscle area and skeletal muscle index (SMI, skeletal muscle area normalized for patient height). Sarcopenia was defined as a SMI <39 cm²/m². Percent change in body composition measures and change in sarcopenia were analyzed for association with death and disease progression based on fitting Cox proportional hazards models. <h3>Results:</h3> We identified 116 patients who underwent PDS followed by adjuvant chemotherapy from 2006-2016 at a large volume single institution. Most patients (73%) had 6 cycles of adjuvant platinum-based chemotherapy. A post-treatment CT scan was obtained at a median of 25 days following the last day of treatment. Overall, there was a decrease in the mean skeletal muscle area and skeletal muscle index, with a percent change of 2.6% from pre- to post-treatment CT scans. Almost half of patients (54/116; 47%) were sarcopenic at some point during their treatment. Of the 116 patients, 62 (53%) were never sarcopenic, 5 (4%) were initially sarcopenic but not at the time of post-treatment scan, 28 (24%) were sarcopenic on both CT scans, and 21 (18%) were only sarcopenic at the time of post-treatment CT scan.The 21 patients who became sarcopenic during the course of treatment were more likely to have an American Society of Anesthesiologists physical status score more than 2 (62% vs 43%), preoperative albumin <3.5 g/dL (24% vs 14%), stage IV disease (48% vs 21%) and to have undergone a high complexity surgery (57% vs 33%). Developing sarcopenia during treatment was associated with both an increased risk of disease progression (HR=1.43; 95% CI 0.85-2.40; p=0.18) and death (HR=1.78; 95% CI 1.00-3.18; p=0.05) when compared to all others (Figure). The development of sarcopenia following treatment was the strongest predictor of death compared to the 4 aforementioned factors. <h3>Conclusions:</h3> We observed that sarcopenia changes during the course of treatment among EOC patients who underwent curative intent PDS and adjuvant chemotherapy. Patients who develop sarcopenia following treatment appear to be at increased risk for poor oncologic outcomes. The cause of sarcopenia in EOC is unclear, and may reflect worse tumor biology or other patient specific factors.