Hypothesis-driven salvage therapy with corticosteroids, tofacitinib, and nintedanib for progressive radiation pneumonitis with possible immune-mediated contribution: a case report.

Sequential or concurrent thoracic radiotherapy and immune checkpoint inhibitors (ICIs) increase the risk of severe overlapping pulmonary toxicity. Progressive pneumonitis after thoracic radiotherapy and ICI exposure remains a clinically challenging condition, particularly when it shows an inadequate response to systemic corticosteroid therapy. We report a 65-year-old man with esophageal cancer who developed progressive radiation pneumonitis with possible immune-mediated contribution after pembrolizumab therapy and thoracic radiotherapy. Despite moderate-dose systemic corticosteroid therapy, he experienced rapid clinical and radiographic deterioration. Laboratory evaluation showed a hyper-inflammatory phenotype, with elevated interleukin-6, ferritin, and C-reactive protein levels. Based on this hyper-inflammatory profile, we initiated a hypothesis-driven salvage regimen comprising corticosteroid therapy, the JAK inhibitor tofacitinib, and nintedanib. This intervention was associated with symptomatic improvement, declining inflammatory biomarkers, and near-complete radiographic resolution. No clinically evident severe treatment-related adverse events were observed during follow-up. Transient diarrhea occurred after nintedanib initiation and improved after dose reduction. This case suggests that biologically rational integration of JAK inhibition and anti-fibrotic therapy may be considered as a hypothesis-driven salvage approach in selected patients with progressive radiation pneumonitis with possible immune-mediated contribution after inadequate response to systemic corticosteroid therapy.