Simple Clinical Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy in Lung Cancer: A Pooled Analysis of 70 Studies

Abstract

radiation therapy (SABR) from a toxicity standpoint, with RTOG 0813 designed to help address this issue. Here we report our institution’s experience in treating central lung tumor patients with SABR, compared to similarly treated peripheral lung tumors. Materials/Methods: We retrospectively reviewed outcomes in 82 patients with 96 primary or metastatic lung tumors treated by SABR. The cohort included 47 central and 49 peripheral tumors; all were treated with 50 Gy in 4 to 5 fractions. Outcomes, toxicities, and dosimetric parameters were compared between the 2 groups, not including patients in whom central and peripheral tumors were concurrently treated (8 such patients). Results: Median follow-up time was 15 months (range 1 to 59 months). Median overall survival was 34 and 40 months (PZ.75) for patients with central and peripheral tumors, respectively. We observed no hemoptysis, and no grade 5 toxicities. Rates of symptomatic (grade 2+) toxicity were higher in patients with central tumors by both univariate analysis (38% vs 11%, PZ.0056, HRZ3.7) and multivariate analysis (PZ.02, HRZ3.9), but were equivalent for severe (grade 3+) toxicity (5.4% vs 5.4%, PZ.93, HRZ1.1). The vast majority of observed toxicities were due to symptomatic pneumonitis, incidence of which was significantly greater in patients with central tumors by both univariate analysis (30% vs 2.7%, PZ.0021, HRZ6.5) and multivariate analysis (PZ.02, HRZ11.1). These patients also had higher rates of severe pneumonitis that trended towards significance (5.4% vs 0, PZ.15, HRZ7.6). Dosimetric analysis revealed that the central tumor patients in our study experienced significantly greater ipsilateral mean lung doses than their peripheral tumor counterparts (7.33 vs 5.15 Gy, PZ.0058). Total mean lung dose and total lung V20 were not significantly different between the 2 populations. Further analysis of the 35 available central tumor treatment plans revealed that 23 (66%) exceeded at least 1 of the dose constraints used in RTOG 0813, most commonly for central airway. Rates of symptomatic pneumonitis were not significantly different between patients exceeding RTOG 0813 central airway dosing constraints versus those meeting them (25% vs 20%, PZ.64), but trended towards significance for severe pneumonitis, with patients exceeding RTOG 0813 central airway dose constraints experiencing higher rates (0 vs 13%, PZ.10). Conclusions: Central lung tumor patients treated with SABR appear to experience higher rates of symptomatic pneumonitis compared to patients with peripherally located lung tumors, which grossly correlates with increased ipsilateral mean lung dose. Exceeding RTOG 0813 dosimetric constraints for central airway may predispose to higher risk for severe radiation pneumonitis. Author Disclosure: A. Chaudhuri: None. C. Tang: None. N. Trakul: None. J. Wynne: None. B.W. Loo: E. Research Grant; Varian, RaySearch Laboratories. F. Honoraria; Varian. M. Diehn: E. Research Grant; Varian, RaySearch Laboratories. F. Honoraria; Varian. G. Consultant; Varian.