PurposeThe purpose of this retrospective cohort study was to evaluate the effect of tumor location and other major factors on the risk of complications from stereotactic body radiation therapy (SBRT) in non-small cell lung cancer (NSCLC) patients with a history of thoracic surgery and/or radiation therapy.MethodsMedical records of patients with recurrent or second primary NSCLC treated with SBRT between 2005 and 2015 were reviewed. All patients had prior thoracic surgery and/or radiation therapy and were treated with image-guided, robotic SBRT. Time to local failure and toxicity was evaluated by using cumulative incidence and competing risk regression analysis. Overall survival was estimated using the Kaplan-Meier method.ResultsFifty-six patients with 74 tumors treated with SBRT were included for analysis. Of the 74 tumors, 19 (26%) were centrally located within 2 cm of the proximal bronchial tree. At a median follow-up of 27 months (range = 5–129), the 2-year cumulative incidence of LF was 13% for peripheral tumors and 16% for central tumors (p = 0.95). Neither prior thoracic surgery nor radiation therapy was associated with increased LF or toxicity. Among the 56 patients, eight (14%), three (5%), and one (2%) experienced grade 2, 3, and 4 complications following SBRT. Patients with a ≥ 50 pack-year smoking history were more likely to develop ≥ grade 2 toxicity (HR 5.3; 95% CI 1.4–19.9, p = 0.01). Central tumor location was associated with higher risk of toxicity (HR 3.4; 95% CI 1.1–10.5, p = 0.04) as was planning tumor volume > 30 mL (HR 4.3; 95% CI 1.1–16.3, p = 0.047). In a multivariable model, central location remained significant after adjusting for smoking history and planning tumor volume.ConclusionsAfter prior thoracic surgery and/or radiation, SBRT retreatment for NSCLC provided durable local control and was well tolerated in most patients. Patients with a history of previously operated and/or radiated lung cancer with new central tumors, PTV volume > 30 mL, or smoking history ≥ 50 pack-years were at higher risk of complications from SBRT.