Radiation-triggered acute exacerbation of progressive fibrotic interstitial lung diseases: ‘Are we advancing the frontier or crossing a dangerous line?’

Fibrotic interstitial lung diseases (F-ILDs) are increasingly complicated by early-stage non-small cell lung cancer. For many of these patients, stereotactic ablative body radiotherapy (SABR) is the only feasible curative-intent option. However, pre-existing fibrosis markedly increases the risk of severe, sometimes fatal, post-treatment respiratory events. These episodes are usually labelled radiation pneumonitis (RP), yet their timing, distribution and lethality often resemble acute exacerbations (AEs) of the underlying interstitial lung disease (ILD) rather than classical, field-confined RP. In this narrative review, we synthesise observational data from the SABR series enriched for ILD, focusing on acute respiratory deterioration within weeks to months after treatment. We examine how inconsistent terminology and heterogeneous case definitions obscure the distinction between RP and radiation-triggered AE (RT-AE)-ILD, and we summarise clinical, radiological, physiological, dosimetric and biomarker risk factors. Mechanistic models suggest that radiation may amplify a primed fibrotic lung via convergent epithelial, endothelial and immune pathways, with potential modulation by antifibrotic therapy, corticosteroid exposure and infection. We argue that in patients with progressive F-ILD, at least a subset of post-SABR 'pneumonitis' episodes are better conceptualised as RT-AE, with implications for corticosteroid stewardship, infection prophylaxis and continuation of antifibrotics. Given the absence of trial-level evidence and the high baseline mortality of F-ILD, management must prioritise multidisciplinary evaluation, explicit shared decision-making and cautious individualisation rather than reflexive transplantation of RP algorithms. Prospective registries, standardised ILD phenotyping and translational studies are urgently needed to define risk boundaries and test whether antifibrotic-radiation strategies or particle therapies can safely deliver curative-intent treatment to this highly vulnerable population.