P1.137. Baseline Skeletal Muscle Depletion Stratifies Treatment Feasibility and Survival in Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Immunochemotherapy

Abstract

Abstract Topic Esophageal Cancer: Other Background Physiological reserve plays a pivotal role in determining the capacity of patients to tolerate intensive multimodal therapy. In locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has become increasingly adopted; however, the prognostic and therapeutic implications of preexisting skeletal muscle depletion in this context remain insufficiently elucidated. Methods In this multicenter real-world cohort, consecutive patients with locally advanced ESCC treated with nICT followed by planned surgery were retrospectively analyzed. Skeletal muscle index (SMI) was quantified from baseline computed tomography at the third lumbar vertebra and normalized for stature. Sex-specific outcome-based thresholds were applied to define low muscle mass. A composite indicator of neoadjuvant treatment feasibility was constructed to reflect dose modification, early discontinuation, and inability to proceed to resection. Associations between skeletal muscle status and treatment delivery, perioperative morbidity, and long-term survival were assessed using multivariable regression models in intention-to-treat and surgical populations. Results Among 461 eligible patients, 121 (26.2%) exhibited low SMI. A substantial proportion of these individuals had body mass index within the normal range, highlighting the presence of occult muscle depletion. Patients with low SMI experienced significantly higher rates of treatment modification, premature termination of neoadjuvant therapy, and failure to undergo curative surgery. They were also more likely to develop severe therapy-related toxicities and major postoperative complications. After adjustment for relevant clinicopathologic variables, low SMI independently predicted worse overall survival and disease-free survival. Notably, postoperative adjuvant immunotherapy appeared to attenuate the adverse prognostic impact of skeletal muscle depletion, whereas no significant survival advantage was observed in patients without low SMI. Conclusion Pretherapeutic skeletal muscle depletion identifies a high-risk host phenotype characterized by compromised neoadjuvant treatment feasibility, increased perioperative morbidity, and inferior survival in locally advanced ESCC. Routine incorporation of quantitative muscle assessment may facilitate early vulnerability detection and support individualized treatment optimization across the perioperative continuum.