Background: Lung dose-volume histogram (DVH) in radiotherapy could be calculated from multiple normal lung definitions. The lung dosimetric parameters generated from various approaches are significantly different. However, limited evidence shows which definition should be used to more accurately predict radiation pneumonitis (RP). We aimed to compare the RP prediction accuracy of dosimetric parameters from three lung volume methods in lung cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT).

Methods: We retrospectively reviewed 183 consecutive lung cancer patients treated with IMRT from January 2014 to October 2017. The normal lungs were defined by total bilateral lung volume (Total Lung), excluding PTV (Lung-PTV) or PGTV (Lung-PGTV). V5, V20, and mean lung dose (MLD) have been extracted from three definitions. The primary endpoint was acute grade 2 or higher RP (RP2). Correlation between RP2 and dose parameters were analyzed by logistic regression. We evaluated prediction performance using area under the receiver operating characteristic curve (AUC) and normal tissue complication probability (NTCP) model.

Results: Twenty-six patients (14.2%) developed acute RP2 after IMRT treatment. Significant dosimetric differences were found between any 2-paired lung volumes (Ps < 0.001). To limit RP2 incidence less than 20%, the cutoff MLDs were 12.5 Gy, 14.2 Gy, and 15.0 Gy, respectively, for Lung-PTV, Lung-PGTV, and Total Lung methods. There were 54% (13% vs. 20%) and 45% (20% vs. 29%) RP2 probability variances detected at each MLD cutoff points from Lung-PTV and Lung-PGTV definitions. The best RP prediction performance was found in MLD from Lung-PTV method (AUC = 0.647), which is significantly better (P = 0.006) than the MLD from Lung-PGTV method (AUC = 0.609).

Conclusion: There are significant differences in acute RP2 rate prediction using dosimetric parameters from various normal lung definitions. Excluding PTV from total lung volume may be more accurate and promising to predict acute symptomatic radiation pneumonitis in IMRT treated lung cancer patients.

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Published in Radiation Oncology, v. 14, article no. 7, p. 1-8.

© The Author(s). 2019

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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This work was funded by the National Natural Science Foundation of China (81874221), Zhejiang Provincial Medicine and Health Foundation (2015KYA240), and Taizhou Science and Technology Bureau (15yw01 and 1802ky07).

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The datasets are available to all interested researchers on reasonable request from corresponding author.