CT-assessed sarcopenia and immune-related adverse events in patients with lung cancer: A competing risk time-to-event analysis.

Background: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). This study investigates the relationship between CT-assessed sarcopenia and irAEs in patients with lung cancer who are receiving ICIs.

Methods: Patients were enrolled if they had lung cancer treated with ICIs at the University Medical Center Groningen (2015-2021) and had undergone low-dose CT scans that included the third lumbar vertebral level (L3). CT-assessed sarcopenia was defined based on reported L3 skeletal muscle mass index (L3SMI) thresholds. Patients were categorized into no, any-grade, and severe irAE groups. The association between CT-assessed sarcopenia and irAEs was assessed by competing risk time-to-event analysis, accounting for the risk of death. Sub-distribution hazard ratios (HR) were calculated using Fine-Gray regression models adjusted for relevant confounders. The association between CT-assessed sarcopenia and overall survival (OS) was evaluated through survival analyses.

Results: We included 363 patients; most were male (60.9 %), had favorable Eastern Cooperative Oncology Group (ECOG) performance statuses (0-1; 90.1 %), had stage IV disease (92.8 %), and received ICI monotherapy (82.9 %). Of these, 45.6 % developed any-grade irAEs and 21 % developed severe irAEs. Endocrine disorders were the most common mild irAEs (24.8 %), while respiratory disorders were the most common severe irAEs (24.7 %). CT-assessed sarcopenia was more prevalent in the no irAE group (87 %) compared with the any-grade (77 %) and severe (79 %) irAE groups. Presence of CT-assessed sarcopenia was associated with a lower risk of developing any irAEs (HR = 0.62 [95 % CI: 0.41-0.92]). No significant association was found between CT-assessed sarcopenia and severe irAEs (fully adjusted model, HR = 0.74 [95 % CI: 0.39-1.4]), or between CT-assessed sarcopenia and OS.

Conclusion: CT-assessed sarcopenia is associated with a reduced risk of any irAEs in patients with lung cancer receiving ICIs, possibly because higher muscle mass enhances the host response to immunological stimulation. Recognizing sarcopenia as a predictive factor for irAEs is relevant for personalizing treatments.