Real-World Data on the Safety and Efficacy of SBRT for Central and Ultra-Central Lung Tumors: A Retrospective Multi-Center Cohort

<b>Background/Objectives</b>: The use of stereotactic body radiotherapy (SBRT) for centrally and ultra-centrally located early-stage non-small cell lung cancer (NSCLC) remains clinically challenging due to the proximity of critical mediastinal organs at risk and the limited prospective evidence, particularly for ultra-central disease. Real-world data are needed to better define the safety and efficacy of SBRT when delivered according to contemporary protocol-based planning principles. <b>Methods</b>: This retrospective cohort study included patients treated at two radiotherapy centers, with centralized follow-up and outcome adjudication at a single academic institution. We evaluated patients with centrally or ultra-centrally located, early-stage NSCLC treated with SBRT according to dose-fractionation and planning principles derived from the NRG Oncology/RTOG 0813 protocol. Tumors were classified as central or ultra-central according to the International Association for the Study of Lung Cancer and HILUS definitions, respectively. The prescribed dose was 50 Gy in five fractions. Primary endpoints were treatment-related toxicity and local progression-free survival (LPFS). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and dosimetric outcomes. Survival endpoints were analyzed using the Kaplan-Meier method. <b>Results</b>: Seventy-eight patients were included, of whom 52 had centrally located and 26 ultra-centrally located tumors. Median follow-up was 57 months. The overall objective response rate was 92.3%. The estimated 4-year LPFS was 97.4% for the entire cohort, with rates of 100% for central and 91.6% for ultra-central tumors (<i>p</i> < 0.001). Four-year OS was 98.7%, with no treatment-related deaths observed. Treatment-related toxicity was minimal, with grade ≥ 2 events occurring in only one patient (1.3%) and no grade ≥ 3 toxicity. All treatment plans met predefined organ-at-risk dose constraints. <b>Conclusions</b>: In this real-world cohort, SBRT delivered according to RTOG 0813 planning principles achieved excellent local control with minimal clinically relevant toxicity in patients with centrally and ultra-centrally located early-stage NSCLC. These findings support the safe implementation of SBRT in carefully selected patients when stringent organ-at-risk constraints and conservative treatment planning are employed.