Muscle loss and pentraxin-3 as predictors of immunotherapy outcomes in non-small cell lung cancer: a prospective study.

Sarcopenia has been reported that as a prognostic factor in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs), mainly based on retrospective, imaging-based analyses. However, its prognostic value has not been prospectively evaluated. In this prospective study we investigated the clinical impact of sarcopenia and explored circulating proteins associated with muscle loss and ICI outcomes. Patients with advanced NSCLC who received ICIs as first-line therapy were enrolled. Before treatment initiation, muscle mass was assessed using bioelectrical impedance analysis, together with grip strength, walking speed, and physical activity. Pretreatment plasma samples were subjected to comprehensive protein profiling. Between October 2019 and August 2022, 41 patients were enrolled. Bothe overall survival and progression-free survival were significantly shorter in patients with sarcopenia. Notably, patients with pre-sarcopenia, defined as reduced muscle mass without impairment of muscle strength or physical performance, also exhibited poor clinical outcomes. Protein analysis identified penraxin-3 as being significantly associated with muscle loss and overall survival. These findings demonstrate, for the first time in a prospective setting, that even pre-sarcopenia is associated with poor prognosis in NSCLC patients treated with ICIs, and suggest that pentraxin-3 may serve as a biomarker linking sarcopenia to unfavorable outcomes.