Central Airway Toxicity After High Dose Radiation: A Combined Analysis of Prospective Clinical Trials for Non-Small Cell Lung Cancer.

PURPOSE To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiotherapy for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS Patients with medically inoperable/unresectable NSCLC treated with conventionally fractionated 3D conformal radiotherapy (3DCRT) in prospective clinical trials were eligible for this study. PBT and PBT wall (PBTW) were contoured consistently per RTOG 1106 OAR-Atlas. The dose-volume histograms (DVHs) of physical prescription dose (DVHp) and biological effective dose (α/β=2.5, DVH2.5) were generated respectively. The primary endpoint was PBT toxicities, defined by CTCAE 4.0 under the terminology of bronchial stricture/atelectasis. RESULTS Of a total of 100 patients enrolled, with a median follow-up of 64 (95% CI, 50-78) months, 73% received 70 Gy or above, and 17% developed PBT toxicity (Grade 1, 8%; Grade 2, 6%; Grade 3, 0% and Grade 4, 3%). The median time interval between RT initiation and onset of PBT toxicity was 8.4 (95% CI, 4.7-44.1) months. The combined DVHs showed that no patient with a PBT maximum physical dose <65 Gy developed any PBT toxicity. Cox proportional hazards analysis and receiver operating characteristic analysis demonstrated that V75 of PBT was the most significant dosimetric parameter for both Grade 1+ (P=0.035) and Grade 2+ (P=0.037) PBT toxicities. The dosimetric thresholds for V75 of PBT were 6.8% and 11.9% for Grade 1+ and Grade 2+ PBT toxicity, respectively. CONCLUSIONS V75 of PBT appeared be the most significant dosimetric parameter for PBT toxicity after conventionally fractionated thoracic 3DCRT. Constraining V75 of PBT may limit clinically significant PBT toxicity.