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

Abstract

Purpose: To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).

Methods and materials: Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall 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 100 patients enrolled, with a median follow-up of 64 months (95% confidence interval [CI], 50-78), 73% received 70 Gy or greater 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 months (95% CI, 4.7-44.1). 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 = .035) and grade 2+ (P = .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 can limit clinically significant PBT toxicity.

Figure 1.

Combined Dose-Volume Histograms (DVHs) of proximal bronchial tree (A) and proximal bronchial tree wall (B) for 100 patients.

Figure 2.

Dose-Volume Histograms (DVHs) atlas plots for (A) Grade 1+ and (B) Grade 2+ PBT toxicity.

Figure 3.

Receiver operating characteristic (ROC) analysis of Dose-Volume Histograms (DVHs) parameters for PBT toxicity Grade 1+ (A, C) and Grade 2+ (B, D).

Figure 4.

Kaplan-Meier cumulative incidence plots for Grade 1+ (A) and Grade 2+ (B) PBT toxicity with optimal cutoff values of V75 of PBT. PBT, proximal bronchial tree; V75, volumes receiving doses greater than 75 Gy.