Abstract
PURPOSE: This study aims to evaluate the cumulative equivalent dose in 2 Gy fractions (EQD2) to organs at risk and its potential correlation with toxicities in patients with locally advanced nonsmall cell lung cancer treated with very high mediastinal radiation therapy doses using mixed fractionation. METHODS AND MATERIALS: Patients from a previously reported phase 1 trial (PMID: 29650404) were included (n = 26). They received a stereotactic boost (3 × 7-12 Gy) following chemoradiation therapy (cisplatin-based chemotherapy and 23 × 2 Gy using three-dimensional conformal radiation therapy). Seventeen treatment plans were available for dosimetric analysis. Doses delivered at each point of the planning computed tomography scan from each treatment phase were converted to EQD2 based on the α:β ratios, which are shown in asterisks following each converted dose. The 3-dimensional conformal radiation therapy and stereotactic body radiation therapy plans were each converted to EQD2, and their summation was used to estimate the total dose delivered to organs at risk. RESULTS: In the entire cohort (n = 26), 77% of tumors were ultracentral, 19% peripheral, and 4% central. We observed 1 grade 3 toxicity (bronchial stenosis/fibrosis), 1 grade 4 toxicity (esophagitis with fistula), and 1 grade 5 toxicity (fatal hemoptysis). Dosimetric evaluation of the proximal bronchovascular (PBV) tree and esophagus revealed no severe late toxicity with PBV tree D1cc < 150 Gy *2* and esophageal D1cc < 100 Gy *10*. Median maximal EQD2 D1cc for organs at risk were as follows: aorta, 84.3 Gy *3* (range, 53.3-190.6); pulmonary arteries, 136.9 Gy *3* (range, 47.2-232.3); superior vena cava, 70.6 Gy *3* (range, 16.2-192.8); pulmonary veins, 69.0 Gy *3* (range, 3.5-231); esophagus, 67.9 Gy *10* (range, 15.7-161); PBV tree, 153.4 Gy *2* (range, 20.3-235.9). CONCLUSIONS: The following preliminary dose constraints-PBV tree D1cc < 150 Gy *2* and esophageal D1cc < 100 Gy *10*-may be safe and are currently being prospectively evaluated in an ongoing phase 2 trial (NCT06627738). The correlation between toxicities and the degree of initial tumor infiltration of organs at risk requires further prospective evaluation.