Abstract

ObjectivesWe aimed to explore the synergistic combination of a topologically invariant Betti number (BN)-based signature and a biomarker for the accurate prediction of symptomatic (grade ≥2) radiation-induced pneumonitis (RP+) before stereotactic ablative radiotherapy (SABR) for lung cancer.MethodsA total of 272 SABR cases with early-stage non-small cell lung cancer were chosen for this study. The occurrence of RP+ was predicted using a support vector machine (SVM) model trained with the combined features of the BN-based signature extracted from planning computed tomography (pCT) images and a pretreatment biomarker, serum Krebs von den Lungen-6 (BN+KL-6 model). In all, 242 (20 RP+ and 222 RP–(grade 1)) and 30 cases (8 RP+ and 22 RP–) were used for training and testing the model, respectively. The BN-based features were extracted from BN maps that characterize topologically invariant heterogeneous traits of potential RP+ lung regions on pCT images by applying histogram- and texture-based feature calculations to the maps. The SVM models were built to predict RP+ patients with a BN signature that was constructed based on the least absolute shrinkage and selection operator logistic regression model. The evaluation of the prediction models was performed based on the area under the receiver operating characteristic curves (AUCs) and accuracy in the test. The performance of the BN+KL-6 model was compared to the performance based on the BN, conventional original pCT, and wavelet decomposition (WD) models.ResultsThe test AUCs obtained for the BN+KL-6, BN, pCT, and WD models were 0.825, 0.807, 0.642, and 0.545, respectively. The accuracies of the BN+KL-6, BN, pCT, and WD models were found to be 0.724, 0.708, 0.591, and 0.534, respectively.ConclusionThis study demonstrated the comprehensive performance of the BN+KL-6 model for the prediction of potential RP+ patients before SABR for lung cancer.

Highlights

  • Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment for early-stage nonsmall cell lung cancer (NSCLC)

  • The test area under the receiver operating characteristic curves (AUCs) obtained for the Betti number (BN)+Krebs von den Lungen-6 (KL-6), BN, planning computed tomography (pCT), and wavelet decomposition (WD) models were 0.825, 0.807, 0.642, and 0.545, respectively

  • This study demonstrated the comprehensive performance of the BN signature and KL-6 (BN+KL-6) model for the prediction of potential RP+ patients before SABR for lung cancer

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Summary

Introduction

Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment for early-stage nonsmall cell lung cancer (NSCLC). Most cases of RP are manageable, a few cases are severe, and there is a risk of mortality [3] This raises the demand for predicting the occurrence of RP+ before SABR to support radiation oncologists in decision-making for radiotherapy. An antigen Krebs von den Lungen-6 (KL-6), mucin-like glycoprotein, has been recognized as a biomarker of pulmonary epithelial cell injury [5–8]. Besides it is widely known for its association with the activity of interstitial pneumonia (IP), a number of studies reported the usefulness of the KL-6 for the prediction of RP+ prior to SABR [5–7, 9]. Since KL-6 is associated with RP+ as well as the existence of lung cancer itself [10, 11], the predictive performance of pretreatment KL-6 may not be sufficient (S1 Table)

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