Enhanced prediction of postoperative radiotherapy-induced esophagitis in non-small cell lung cancer: Dosiomic model development in a real-world cohort and validation in the PORT-C randomized controlled trial

Abstract

Background: Radiotherapy-induced esophagitis (RE) diminishes the quality of life and interrupts treatment in patients with non-small cell lung cancer (NSCLC) undergoing postoperative radiotherapy. Dosimetric models showed limited capability in predicting RE. We aimed to develop dosiomic models to predict RE.

Methods: Models were trained with a real-world cohort and validated with PORT-C randomized controlled trial cohort. Patients with NSCLC undergoing resection followed by postoperative radiotherapy between 2004 and 2015 were enrolled. The endpoint was grade ≥2 RE. Esophageal three-dimensional dose distribution features were extracted using handcrafted and convolutional neural network (CNN) methods, screened using an entropy-based method, and selected using minimum redundancy and maximum relevance. Prediction models were built using logistic regression. The areas under the receiver operating characteristic curve (AUC) and precision-recall curve were used to evaluate prediction model performance. A dosimetric model was built for comparison.

Results: A total of 190 and 103 patients were enrolled in the training and validation sets, respectively. Using handcrafted and CNN methods, 107 and 4096 features were derived, respectively. Three handcrafted, four CNN-extracted and three dosimetric features were selected. AUCs of training and validation sets were 0.737 and 0.655 for the dosimetric features, 0.730 and 0.724 for handcrafted features, and 0.812 and 0.785 for CNN-extracted features, respectively. Precision-recall curves revealed that CNN-extracted features outperformed dosimetric and handcrafted features.

Conclusions: Prediction models may identify patients at high risk of developing RE. Dosiomic models outperformed the dosimetric-feature model in predicting RE. CNN-extracted features were more predictive but less interpretable than handcrafted features.

Keywords: convolution neural network; dosiomics; non-small cell lung cancer; prediction model; radiation esophagitis.

FIGURE 1

AUC and Fn feature values. AUC as a function of Fn values of handcrafted (a) and CNN‐extracted (b) features are shown. For each specific Fn, the logistic regression model was hyperparameter‐tuned, and the mean AUC of 100 bootstraps was calculated, along with the 95% confidence interval. The value of Fn was tuned from 1 to 10. AUC, area under receiver operating characteristic curve; CNN, convolutional neural network; Fn, number of features.

FIGURE 2

ROC analysis. ROC curves of dosimetric features (a), handcrafted features (b), and CNN‐extracted features (c) are shown. CNN, convolutional neural network; ROC, receiver operating characteristics.

FIGURE 3

Precision‐recall curves. Curves of dosimetric (a), handcrafted (b), and CNN‐extracted (c) features are shown. CNN, convolutional neural network.