Intermediate Dose-Volume Parameters, Not Low-Dose Bath, Is Superior to Predict Radiation Pneumonitis for Lung Cancer Treated With Intensity-Modulated Radiotherapy

Yinnan Meng,Haihua Yang,Liqiao Hou,Chao Zhou,Wei Wang,Suna Zhou,Wei Luo,Xingni Tang,Feng-Ming Spring Kong

doi:10.3389/fonc.2020.584756

Abstract

PurposeAlthough intensity-modulated radiotherapy (IMRT) is now a preferred option for conventionally fractionated RT in lung cancer, the commonly used cutoff values of the dosimetric constraints are still mainly derived from the data using three-dimensional conformal radiotherapy (3D-CRT). We aimed to compare the prediction performance among different dosimetric parameters for acute radiation pneumonitis (RP) in patients with lung cancer received IMRT.MethodsA total of 236 patients treated with IMRT were retrospectively reviewed in two independent groups of lung cancer from January 2014 to August 2018. The primary endpoint was grade 2 or higher acute RP (RP2). Dose metrics were generated from the bilateral lung volume outside GTV (VdoseG) and PTV (VdoseP). The associations of RP2 with clinical variables, dose-volume parameters and mean lung dose (MLD) were analyzed by univariate and multivariate logistic regression. The power of discrimination among each predictor was assessed by employing the bootstrapped area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and the integrated discrimination improvement (IDI).ResultsThirty-four (14.4%) out of 236 patients developed acute RP2 after the end of IMRT. The clinical parameters were identified as less important predictors for RP2 based on univariate and multivariate analysis. In both studied groups, the significance of association was more convincing in V20P, V30P, and MLDP (smaller Ps) than V5G and V5P. The largest bootstrapped AUC was identified for the V30P. We found a trend of better discriminating performance for the V20P and V30P, and MLDP than the V5G and V5P according to the higher values in AUC, IDI, and NRI analysis. To limit RP2 incidence less than 20%, the V30P cutoff was 14.5%.ConclusionsThis study identified the intermediate dose-volume parameters V20P and V30P with better prediction performance for acute RP2 than low-dose metrics V5G and V5P. Among all studied predictors, the V30P had the best discriminating power, and should be considered as a supplement to the traditional dose constraints in lung cancer treated with IMRT.

Highlights

Acute radiation pneumonitis (RP), a challenging dose-limiting toxicity, commonly occurs within 1 to 6 months after the completion of thoracic radiotherapy (RT) [1, 2]
In the intensity-modulated radiotherapy (IMRT)-adaptive radiotherapy (ART) group, only the parameters of volume exceeding 20 Gy (V20), V30, and mean lung dose (MLD) from both lung volumes were confirmed to be significantly associated with RP2 (Figure 1B)
This study demonstrated that the V30P had the best RP2 prediction performance among all dosimetric parameters in two independent groups

Summary

Introduction

Acute radiation pneumonitis (RP), a challenging dose-limiting toxicity, commonly occurs within 1 to 6 months (most often within 12 weeks) after the completion of thoracic radiotherapy (RT) [1, 2]. The quantitative analyses of normal tissue effects in the clinic (QUANTEC) lung project reviewed over 70 articles published before 2010 and provided the most reliable dose-RP relationship models to overcome the inconsistency [4]. The majority of evidence in the QUANTEC was based on threedimensional conformal radiation therapy (3D-CRT), which may not well represent the dose distributions delivered by the more advanced techniques, such as intensity-modulated radiotherapy (IMRT). Ten years have passed since the QUANTEC, and there is a need to investigate more accurate dose predictors based on new data emerging from IMRT

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