External validation of pulmonary radiotherapy toxicity models for ultracentral lung tumors

INTRODUCTION: Pulmonary toxicity is dose-limiting in stereotactic body radiation therapy (SBRT) for tumors that abut the proximal bronchial tree (PBT), esophagus, or other mediastinal structures. In this work we explored published models of pulmonary toxicity following SBRT for such ultracentral tumors in an independent cohort of patients. METHODS: The PubMed database was searched for pulmonary toxicity models. Identified models were tested in a cohort of patients with ultracentral lung tumors treated between 2008 and 2017 at one large center (N = 88). This cohort included 60 % primary and 40 % metastatic tumors treated to 45 Gy in 5 fractions (fx), 50 Gy in 5 fx, 60 Gy in 8 fx, or 60 Gy in 15 fx prescribed as 100 % dose to PTV. RESULTS: Seven published NTCP models from two studies were identified. The NTCP models utilized PBT max point dose (Dmax), D0.2 cm(3), V65, V100, and V130. Within the independent cohort, the ≥ grade 3 toxicity and grade 5 toxicity rates were 18 % and 7–10 %, respectively, and the Dmax models best described pulmonary toxicity. The Dmax to 0.1 cm(3) model was better calibrated and had increased steepness compared to the Dmax model. A re-planning study minimizing PBT 0.1 cm(3) to below 122 Gy in EQD2(3) (for a 10 % ≥grade 3 pulmonary toxicity) was demonstrated to be completely feasible in 4/6 patients, and dose to PBT 0.1 cm(3) was considerably lowered in all six patients. CONCLUSIONS: Pulmonary toxicity models were identified from two studies and explored within an independent ultracentral lung tumor cohort. A modified Dmax to 0.1 cm(3) PBT model displayed the best performance. This model could be utilized as a starting point for rationally constructed airways constraints in ultracentral patients treated with SBRT or hypofractionation.