EQD2-adjusted mean lung dose and symptomatic pneumonitis after thoracic radiotherapy following immune checkpoint inhibitors in lung cancer: a single-center retrospective cohort study

Background Evidence on pneumonitis after thoracic radiotherapy following immune checkpoint inhibitor (ICI) exposure remains limited. We examined associations with voxel-wise EQD2 mean lung dose (MLD EQD2 ) and the ICI–radiotherapy interval. Methods This single-center retrospective cohort included 98 patients in a 90-day competing-risk analysis of grade ≥2 radiation pneumonitis (CTCAE), comprising 26 pneumonitis events, 70 event-free observations, and two deaths before pneumonitis. Archived DICOM doses were converted voxel-wise using α/β = 3 Gy. Cumulative incidence was estimated using the Aalen–Johansen method, and Fine–Gray regression included continuous MLD EQD2 and treatment interval. Supplementary logistic analyses included 96 patients. Results The 90-day pneumonitis cumulative incidence was 26.5% (95% CI 17.7%–35.3%). The adjusted subdistribution hazard ratio (SHR) for MLD EQD2 was 1.339 per Gy (95% CI 1.113–1.612; P = 0.002). The interval SHR was 0.784 per 10 days (95% CI 0.639–0.963; P = 0.020). Physical MLD showed a consistent association (SHR 1.197 per Gy, 95% CI 1.036–1.382; P = 0.015). Conclusion Higher MLD EQD2 and shorter treatment intervals were associated with grade ≥2 symptomatic pneumonitis in this treatment sequence. Clinical ascertainment and dose-reconstruction uncertainties limit interpretation. The absence of an ICI-naive comparator precludes conclusions about ICI-specific radiosensitization. Prospective validation is required before these associations can inform dose constraints or treatment scheduling.