ORIGINAL RESEARCH A risk model for lung complication combining radiation therapy and chronic obstructive pulmonary disease Roman O. Kowalchuk 1 & Daniel M. Trifiletti 1,2 & Shiv R. Khandelwal 1 & James M. Larner 1 & W. Tyler Watkins 1 Received: 10 January 2019 /Accepted: 17 April 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose To develop a multi-variate risk model of lung complication for the treatment of locally advanced lung cancer combining radiation dosimetry and patient-specific risk factors including chronic obstructive pulmonary disease (COPD). Materials/methods A retrospective study of 89 advanced lung cancer patients including clinical variables and radiation dose- volume metrics was correlated to overall survival (OS), local progression-free survival (LPFS), and lung complications. Lung toxicities were defined as grade 2 or higher lung complication including persistent cough requiring narcotic or antitussive agents, and dyspnea with minimal effort but not at rest. Grade 2 or higher radiation pneumonitis (RP) was defined clinically or radiographically. Each observed complication was correlated to the set of patient-specific factors via regression. Results Age was the dominant factor in survival analysis; in patients > 70, 2-year survival was 28% (N = 18) vs. 59% in patients < 70 (N = 71, HR = 3.9, p = 0.004). OS and LPFS were not significantly different based on with COPD status (p = 0.2, HR = 1.5) or radiation dose (range 40–74 Gy, median = 60 Gy, p > 0.5, HR < 1.3). In predicting all observed lung complications, multi- variate stepwise logistic regression revealed COPD status (p = 0.01) and a total lung V50 (p = 0.02) as significant. Separation of G2 or higher lung complication and RP showed a different trend, with G2 or higher lung complication statistically associated with age (p = 0.02) and COPD (p = 0.03). Radiation pneumonitis was only associated with total lung volume at 20 Gy (V20, p = 0.003), with a resulting model risk (RP) = 1.4 (V20-0.21). Conclusions COPD status was not associated with survival or radiation pneumonitis. Age was the dominant factor in survival, and total lung V20 was associated with risk of RP. Keywords Lung cancer . COPD . Pneumonitis . Lung complication Introduction The risk of radiation pneumonitis (RP) is dose-limiting toxic- ity for lung cancer patients receiving thoracic radiation thera- py (RT). The dose-response relationship of the lung has been studied extensively via a meta-analysis of outcomes (e.g., QUANTEC [1]) and normal tissue complication (NTCP) modeling [2–6]. Many of these models suggest a critical dose-volume level or alternatively an effective dose, above which the incidence of RP is considered to be prohibitively high [7]. These models have largely ignored initial lung func- tion, even though pulmonary function testing and chronic ob- structive pulmonary disease (COPD) diagnosis are routinely performed for patients with lung cancer [8]. We propose a risk model of lung complication which includes COPD as a pre- dictive factor for lung complication. * Roman O. Kowalchuk rok4nm@virginia.edu Daniel M. Trifiletti Trifiletti.Daniel@mayo.edu Shiv R. Khandelwal SRK6V@virginia.edu James M. Larner jml2p@virginia.edu W. Tyler Watkins watkinswt@virginia.edu 1 Department of Radiation Oncology, University of Virginia, 1300 Jefferson Park Ave, Charlottesville, VA 22908, USA 2 Radiation Oncology, Mayo Clinic, Jacksonville, FL 22908, USA Journal of Radiation Oncology https://doi.org/10.1007/s13566-019-00386-y