Effect of Longitudinal Changes of Cachexia on the Efficacy and Toxicity of Immune Checkpoint Inhibitors in Esophageal Squamous Cell Cancer (ESCC) Patients

Purpose Immune checkpoint inhibitors (ICIs) have enhanced survival in advanced esophageal squamous cell cancer (ESCC) patients, but their efficacy varies. Cachexia, characterized by muscle loss and significant weight drop, might influence ICI response. This study examines the relationship between cachexia's longitudinal changes and ICI outcomes in ESCC patients. Methods ESCC patients undergoing at least two ICI cycles from 2017-2021 were studied. Cachexia's baseline and evolving patterns during ICI treatment were observed. Kaplan-Meier and Cox regression analyses assessed cachexia's effect on ICI efficacy. Chi-square tests determined cachexia's link to immune-related adverse effects (irAEs). Results 278 ICI-treated patients had median progression-free survival (PFS) of 5.78 months and overall survival (OS) of 8.3 months. Pre-treatment cachexia led to worse outcomes: PFS 7.87 vs. 5.3 months, time to progression (TTP) 10.9 vs. 6.1 months, and OS 14.3 vs. 9.2 months. Irreversible cachexia showed the poorest results. Cachexia's changes weren't associated with irAEs. Conclusion Baseline and evolving cachexia significantly impact ICI efficacy in ESCC patients. Continuous cachexia monitoring during ICI therapy is crucial for optimal ESCC management.