Sarcopenia as a Predictor of Neoadjuvant Therapy-Related Toxicity in Esophageal Squamous Cell Carcinoma Patients

Abstract

Sarcopenia, characterized by loss of muscle mass, plays a critical role in patients with esophageal squamous cell cancer (ESCC). Preoperative chemoradiotherapy and immunotherapy in ESCC patients has been reported to improve survival. Therefore, we sought to evaluate the predictive value of preoperative sarcopenia for toxicity and pathological tumor response to neoadjuvant therapy (NAT) in ESCC patients. A retrospective analysis was performed using a prospectively collected patient cohort of an academic cancer center diagnosed with cT2-4N0-3M0 ESCC between 2019-2022 and treated with neoadjuvant chemoradiotherapy ± pembrolizumab. Sarcopenia was assessed by skeletal muscle index at the third lumbar vertebra in computed tomography scans before NAT (men: 43cm²/m² for body mass index (BMI) < 25kg/m², 53cm²/m² for BMI≥25 kg/m²; women: 41cm²/m²). Logistic regression was performed to assess the association between sarcopenia and preoperative therapy-related toxicity and tumor response. The study included 59 locally advanced ESCC patients (53 male and 6 female), 48 (81.4%) in the non-sarcopenia group, and 11 (18.6%) in the sarcopenia group. Mean age at diagnosis was 62±8 years. Mean BMI at diagnosis was 22.13±2.85 kg/m². 19 patients (32.2%) were stage ⅢA, 25 patients (42.4%) were ⅢB, 15 patients (25.4%) were ⅣA. No significant differences were found between both groups regarding sex, age, BMI, and clinical stage. Acute grade ≥3 toxicity occurred significantly more frequently in the sarcopenia group (54.5% vs. 22.9%, p = 0.045), which mainly included leukopenia, neutropenia, anemia and thrombocytopenia. The discontinuation of NAT owing to toxicity occurred in 8 patients (13.5%), which was significantly associated with sarcopenia (p = 0.003). All patients proceeded to surgery and 33 patients (55.9%) had a pathological complete response (pCR). Univariate analysis revealed no significant association between sarcopenia and pCR (p = 0.071). Among patients with locally advanced EC, sarcopenia is not a predictor of poor NAT response, but it is strongly associated with discontinuation of NAT due to toxicity.