Ablative SABR for Pulmonary Oligometastases in the Era of Contemporary Systemic Therapies: Efficacy, Safety, and Optimal Sequencing

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Purpose: This study evaluated the efficacy and safety of stereotactic ablative radiotherapy (SABR) for pulmonary metastases in the era of contemporary systemic therapy and identified predictors of clinical outcomes and toxicity. Materials and Methods: We retrospectively analyzed 221 patients with 283 lung metastases from non-pulmonary primary cancers who underwent SABR between 2016 and 2024, with 98.2% of lesions treated to a biologically effective dose (BED10) of ≥100 GyE. Local control (LC), progression-free survival (PFS), overall survival (OS), and radiation pneumonitis (RP) were assessed using Cox proportional hazards and logistic regression models. Results: At a median follow-up of 23.7 months, the 1-year LC, PFS, and OS were 96.2%, 46.1%, and 89.5%, respectively. On multivariable analysis, primary cancer site (non-colorectal vs. colorectal: Hazard ratio (HR) 2.49, p=0.025), oligometastatic disease status (de novo vs. repeated: HR 3.14, p=0.026), and pre-SABR cytotoxic chemotherapy (HR 0.08, p=0.006) were identified as independent predictors of LC. Symptomatic RP occurred in 17.0% of cases and was significantly associated with SABR to ≥3 lesions (odds ratio [OR] 2.88, p=0.028), higher lung volume that received ≥10 GyE (OR 1.09, p=0.045), and concurrent administration of high-risk systemic agents, including immune checkpoint inhibitors, cytotoxic agents, or targeted agents (OR 4.01, p=0.015). Conclusion: SABR with predominantly ablative-dose regimens provides excellent LC for pulmonary metastases, influenced by primary tumor biology, oligometastatic disease status, and pre-SABR cytotoxic therapy. The increased risk of symptomatic RP associated with multiple lesions, higher lung dose, and concurrent high-risk systemic agents warrants careful treatment sequencing and cautious monitoring for pulmonary toxicity.

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