The Effectiveness of SBRT for Solitary or Synchronous Multiple Pulmonary Nodules Suspicious of Early-Stage Lung Cancer Without Pathological Confirmation

<b>Background</b>: Stereotactic body radiotherapy (SBRT) is an established curative modality for patients with early-stage non-small cell lung cancer (NSCLC) who are not candidates for surgery. In circumstances where neither surgical resection nor tissue sampling can be performed, SBRT may still be administered empirically, with accumulating evidence indicating excellent efficacy and safety. <b>Objective</b>: This single-institution retrospective study aimed to evaluate the clinical outcomes of SBRT for presumed malignant lung lesions, focusing on local control, survival, and treatment-related toxicity, and to compare these findings with published results in histologically confirmed NSCLC. <b>Methods</b>: Between 2018 and 2024, 80 cases with 85 pulmonary lesions received SBRT at the Department of Oncoradiology, University of Debrecen. All patients underwent comprehensive staging with chest CT and PET-CT, and treatment decisions were made by a multidisciplinary tumor board. Eligibility required the absence of other primary malignancies within 5 years. Treatment planning was based on 4D-CT imaging with internal target volume delineation across multiple respiratory phases. SBRT was delivered on linear accelerators in 4-8 fractions, to a total dose of 48-60 Gy, using volumetric-modulated arc therapy and daily image guidance with 4D cone-beam CT. <b>Results</b>: Most patients presented with solitary lesions, while several had synchronous or metachronous multiple lesions (maximum 3 lesions). The median age was 70.1 years, with 60% ECOG performance status 1. Median follow-up was 21 months. One- and two-year local control rates were 89.8% and 94.3%, respectively, with a 51.4% complete response rate at two years. Mean overall survival was 49.6 months. No grade ≥ 3 toxicities were observed. <b>Conclusions</b>: Empirical SBRT is a safe, well-tolerated, and highly effective treatment option in elderly, inoperable patients with presumed malignant lung lesions. Its favorable efficacy supports its broader use as a curative alternative when histological confirmation is not feasible.