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.