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Title: Function-wise dual-omics analysis for radiation pneumonitis prediction in lung cancer patients
Authors: Li, B
Ren, G 
Guo, W
Zhang, J 
Lam, SK 
Zheng, X
Teng, X 
Wang, Y
Yang, Y
Dan, Q
Meng, L
Ma, Z 
Cheng, C
Tao, H
Lei, H
Cai, J 
Ge, H
Issue Date: 2022
Source: Frontiers in pharmacology, 2022, v. 13, 971849
Abstract: Purpose: This study investigates the impact of lung function on radiation pneumonitis prediction using a dual-omics analysis method.
Methods: We retrospectively collected data of 126 stage III lung cancer patients treated with chemo-radiotherapy using intensity-modulated radiotherapy, including pre-treatment planning CT images, radiotherapy dose distribution, and contours of organs and structures. Lung perfusion functional images were generated using a previously developed deep learning method. The whole lung (WL) volume was divided into function-wise lung (FWL) regions based on the lung perfusion functional images. A total of 5,474 radiomics features and 213 dose features (including dosiomics features and dose-volume histogram factors) were extracted from the FWL and WL regions, respectively. The radiomics features (R), dose features (D), and combined dual-omics features (RD) were used for the analysis in each lung region of WL and FWL, labeled as WL-R, WL-D, WL-RD, FWL-R, FWL-D, and FWL-RD. The feature selection was carried out using ANOVA, followed by a statistical F-test and Pearson correlation test. Thirty times train-test splits were used to evaluate the predictability of each group. The overall average area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and f1-score were calculated to assess the performance of each group.
Results: The FWL-RD achieved a significantly higher average AUC than the WL-RD group in the training (FWL-RD: 0.927 ± 0.031, WL-RD: 0.849 ± 0.064) and testing cohorts (FWL-RD: 0.885 ± 0.028, WL-RD: 0.762 ± 0.053, p < 0.001). When using radiomics features only, the FWL-R group yielded a better classification result than the model trained with WL-R features in the training (FWL-R: 0.919 ± 0.036, WL-R: 0.820 ± 0.052) and testing cohorts (FWL-R: 0.862 ± 0.028, WL-R: 0.750 ± 0.057, p < 0.001). The FWL-D group obtained an average AUC of 0.782 ± 0.032, obtaining a better classification performance than the WL-D feature-based model of 0.740 ± 0.028 in the training cohort, while no significant difference was observed in the testing cohort (FWL-D: 0.725 ± 0.064, WL-D: 0.710 ± 0.068, p = 0.54).
Conclusion: The dual-omics features from different lung functional regions can improve the prediction of radiation pneumonitis for lung cancer patients under IMRT treatment. This function-wise dual-omics analysis method holds great promise to improve the prediction of radiation pneumonitis for lung cancer patients.
Keywords: Dosiomics
Lung functional imaging
Radiation pneumonitis
Radiomics
Radiotherapy
Publisher: Frontiers Research Foundation
Journal: Frontiers in pharmacology 
EISSN: 1663-9812
DOI: 10.3389/fphar.2022.971849
Rights: © 2022 Li, Ren, Guo, Zhang, Lam, Zheng, Teng, Wang, Yang, Dan, Meng, Ma, Cheng, Tao, Lei, Cai and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Li, B., Ren, G., Guo, W., Zhang, J., Lam, S. K., Zheng, X., ... & Ge, H. (2022). Function-Wise Dual-Omics analysis for radiation pneumonitis prediction in lung cancer patients. Computational Intelligence in Personalized Medicine, 110 is available at https://doi.org/10.3389/fphar.2022.971849.
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