Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy

Objective: To investigate the patient and treatment related predictors for the development of radiation induced lung toxicity (RILT) in patients with locally advanced non-small cell lung cancer (NSCLC) receiving definitive three-dimensional radiotherapy. Methods: Data were retrospectively collected from inoperable or unresectable 253 patients with stage III NSCLC treated with definitive three-dimensional radiotherapy between January 2001 and April 2007. National cancer institute common toxicity criteria version 3.0 was employed to evaluate the classification of RILT and grade ≥2 toxicity served as the endpoint. The correlation between RILT and aforementioned factors was analyzed. Results: The grade ≥ 2 RILT was 26.5%. Univariate analysis showed age, FEV1%, DLCO%, contralateral lung (CL) V5 -V15, ipsilateral lung (IL) V5 -V40, total lung (TL) V5 -V50, IL and TL mean lung dose (MLD) were significantly correlated with the development of RILT (χ2 =4.46 - 23.99, P = 0.000 - 0.035). Multivariate analysis showed TL MLD >17.5 Gy and FEV1% ≥72% were significantly correlated with the development of RILT (χ2 = 17.49, 9.30, P = 0.000, 0.002). Patients were stratified into four groups according to MLD and FEV1%, corresponding to the RILT incidence of 9.3%, 24.7%, 38.5% and 63.6%, respectively (χ2 =25.27, P = 0.000). Conclusions: TL MLD and baseline FEV1% are significant factors correlated with the development of RILT in NSCLC patients treated with three-dimensional radiation therapy. The combination of TL MLD and FEV1% may help classify NSCLC patients per risk of RILT and subsequently direct risk-adaptive radiation therapy. Poor baseline pulmonary function does not increase the risk of RILT and may even be associated with lower RILT probability, which has yet to be validated in larger patient cohorts. (authors)