Baseline immune-organ 18F-FDG PET/CT metabolism is associated with immune-related adverse events in anti-PD-1-treated non-small cell lung cancer.

OBJECTIVE: To investigate whether baseline 18F-FDG PET/CT immune-organ metabolic features are associated with immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients receiving anti-PD-1 therapy. METHODS: We retrospectively analyzed 120 stage III-IV NSCLC patients who underwent 18F-FDG PET/CT within 4 weeks before anti-PD-1 therapy and received ≥2 treatment cycles. The endpoint was any-grade irAE (CTCAE v5.0). Candidate predictors included tumor burden; spleen, bone-marrow, and thyroid metabolism; spleen-to-liver ratio (SLR); and bone-marrow-to-liver ratio. Standardized variables entered multivariable logistic regression with bootstrap optimism correction (1,000 resamples) and sensitivity analyses. RESULTS: irAEs occurred in 66 patients (55.0%) after a median of 61.5 days; 18 (27.3%) had grade 3-4 events, mainly pneumonitis and hepatitis. Compared with non-irAE patients, irAE patients showed higher SLR, spleen SUVmax, bone-marrow indices, thyroid SUVmax, and neutrophil-to-lymphocyte ratio (NLR). In the final multivariable model, SLR (odds ratio [OR] 4.13 per 1-SD; 95% CI, 2.28-7.49; p < 0.001), thyroid SUVmax (OR 3.57; 95% CI, 1.96-6.49; p < 0.001), and NLR (OR 2.00; 95% CI, 1.24-3.24; p = 0.005) were independently associated with irAEs. Model AUC was 0.863 (optimism-corrected, 0.850), and persisted after excluding thyroiditis-first cases (AUC 0.874). Discrimination was lower when grade 3-4 events were used as the outcome (AUC 0.724), indicating that the model predicted any-grade irAEs more accurately than severe events. CONCLUSION: Baseline splenic and thyroid FDG metabolism, combined with systemic inflammation, were independently associated with irAEs in anti-PD-1-treated NSCLC, providing candidate pretreatment risk-stratification markers pending external validation.