Radiation-induced cardiac toxicity after SBRT for central and ultracentral lung tumors: A multicenter retrospective cohort study.

Abstract

Central and ultracentral lung tumors are increasingly treated with ablative-dose stereotactic body radiation therapy (SBRT) near cardiac structures, raising concerns regarding radiation-induced heart disease. This study evaluated the prevalence, timing, and clinical factors associated with symptomatic cardiac toxicity following SBRT. This retrospective multicenter cohort included adults treated with SBRT for central or ultracentral lung tumors at three French cancer centers between 2016 and 2023, classified according to SUNSET definitions. Patients with < 6 months of follow-up were excluded from the primary cardiac-toxicity analysis, leaving 162 evaluable patients. Cardiac toxicity was graded using CTCAE v5.0, considering grade ≥ 2 cardiac events occurring ≥ 6 months after SBRT initiation. Variables associated with toxicity at p < 0.10 in univariable analysis were entered into Firth-penalized multivariable logistic regression. Overall survival (OS) was estimated using Kaplan-Meier and explored using Firth-corrected Cox models. Grade ≥ 2 cardiac toxicity occurred in 13 patients (8.0%; 95% CI, 4.7-13.2%), with a median onset of 12.6 months after SBRT. In exploratory multivariable association analysis, prior stroke (OR 4.17; 95% CI, 1.09-15.98) and pulmonary primary tumors (OR 4.03; 95% CI, 1.12-14.42) were associated with cardiac toxicity. At 24 months, lesion-level local control was 78.3%, and OS was 83.4% (95% CI, 73.8-89.7). In exploratory survival analysis, head-and-neck primary tumors and lower prescription EQD₂ were associated with OS. Symptomatic cardiac toxicity after SBRT for central and ultracentral lung tumors was uncommon but clinically relevant. These findings support further evaluation of risk-adapted cardiac monitoring strategies in prospective cohorts.