ArticleFrontiers in immunology2026
Hypothesis-driven salvage therapy with corticosteroids, tofacitinib, and nintedanib for progressive radiation pneumonitis with possible immune-mediated contribution: a case report.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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