Predictors of high-grade radiation pneumonitis following radiochemotherapy for locally advanced non-small cell lung cancer: analysis of clinical, radiographic and radiotherapy-related factors

Abstract Purpose: In this study, the relation between radiation pneumonitis (RP) and a wide spectrum of clinical, radiographic and treatment-related factors was investigated. As scoring of low-grade RP can be subjective, RP grade ≥3 (RP ≥ G3) was chosen as a more objective and clinically significant endpoint for this study. Methods and Materials: 105 consecutive patients with locally advanced non-small cell lung cancer underwent conventionally fractionated radio-(chemo-)therapy to a median dose of 64 Gy. A retrospective analysis of 25 clinical (gender, race, pulmonary function, diabetes, statin use, smoking history), radiographic (emphysema, interstitial lung disease) and radiotherapy dose- and technique-related factors was performed to identify predictors of RP ≥ G3. Following testing of all variables for statistical association with RP using univariate analysis (UVA), a forward selection algorithm was implemented for building a multivariate predictive model (MVA) with limited sample size. Results: Median follow-up of surviving patients was 33 months (9–132 months). RP ≥ G3 was diagnosed in 10/105 (9·5%) patients. Median survival was 28·5 months. On UVA, predictors for RP ≥ G3 were diabetes, lower lobe location, planning target volume, volumetric modulated arc therapy (VMAT), lung V5 Gy (%), lung Vspared5 Gy (mL), lung V20 Gy (%) and heart V5 Gy (% and mL). On MVA, VMAT was the only significant predictor for RP ≥ G3 (p = 0·042). Lung V5 Gy and lung V20 Gy were borderline significant for RP ≥ G3. Patients with RP ≥ 3 had a median survival of 10 months compared to 29·5 months with RP < G3 (p = 0·02). Conclusions: In this study, VMAT was the only factor that was significantly correlated with RP ≥ G3. Avoiding RP ≥ G3 is important as a toxicity per se and as a risk factor for poor survival. To reduce RP, caution needs to be taken to reduce low-dose lung volumes in addition to other well-established dose constraints.