Durable Tumor Control with Multi-Organ Immune-Related Adverse Events Following Immune Checkpoint Inhibitor and Sequential Radiotherapy in Locally Advanced NSCLC: A Case Report

Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) improves survival in stage III non-small cell lung cancer (NSCLC), though immune-related adverse events (irAEs) require vigilant management. Emerging evidence suggests multi-organ irAEs may correlate with favorable outcomes. We report a case of unresectable stage IIIA NSCLC achieving sustained partial response (PR) with progression-free survival (PFS) exceeding 42 months after one cycle of pembrolizumab-chemotherapy followed by sequential thoracic RT (50 Gy/25 fractions). Severe multi-organ irAEs (muscular, cardiovascular, respiratory, hematologic) developed but were effectively managed with corticosteroid-based therapy. Remarkably, durable tumor control persisted despite suboptimal therapeutic dosing and early systemic treatment discontinuation. This case demonstrates that RT-ICI synergy can induce robust systemic antitumor immunity even with dose-reduced RT, while severe multi-system irAEs may signal favorable prognosis. These findings support optimizing RT parameters (eg, dose de-escalation, target volume refinement) as a viable approach in the immunotherapy era.