Identification and Automated Delineation of Radioresistant Biological Tumor Volume in Nasopharyngeal Carcinoma Based on Magnetic Resonance Imaging Radiomics

Abstract

Widespread use of intensity modulated radiotherapy (IMRT) has improved the tumor control rate of nasopharyngeal carcinoma (NPC). However, nearly 20% of the patients with local-advanced NPC would relapse after precise irradiation and 80% of the recurrent lesions occur within the high dose field, suggesting that there are radiation-resistant cancer cell subsets within the tumor. In this context, identification and contouring of radiation resistance region of NPC for dose escalation at primary IMRT could be advantageous. In this work, we proposed a two-step radiomics workflow to predict local relapse and the recurrent region of NPC before primary IMRT. In this single-center, retrospective study, pre-treatment magnetic resonance (MR) sequences of T1-weighted imaging (T1-w) and contrast-enhanced T1-weighted imaging (CET1-w) were collected from 800 patients of newly diagnosed and non-metastatic NPC between April 2009 and December 2015. The primary gross tumor volume (GTVp) of all patients and the actual recurrent lesion (GTVr) of patients who suffered from local recurrence were manually contoured for further analysis. A two-step complete radiomics workflow was designed to predict tumor recurrence and segment the region. First, least absolute shrinkage and selection operator (LASSO) was utilized for radiomics features selection of GTVp and support vector machine (SVM) was adopted to predict the recurrence. If the model predicts a recurrence, then the workflow utilizes an improved 3D U-Net to segment the recurrent region. Area under receiver operating characteristic curve (ROC-AUC) was used to evaluate the performance of tumor recurrence prediction, and Dice similarity coefficient (DSC) was used to assess the consistence between the actual and predicted GTVr. Of 800 NPC patients, 95 (11.9%) patients developed in-field local recurrence. For recurrence risk prediction, the SVM ensemble model (T1-w+CET1-w) was selected for further application with higher sensitivity. The average ROC-AUC, specificity, sensitivity of the SVM ensemble model in a 5-fold cross-validation and in the independent test set of 160 patients were 0.922, 0.922, 0.777 and 0.928, 0.915, 0.737, respectively. Moreover, for recurrent region segmentation, the multi-modality (T1-w+CET1-w) model was superior to the single-modality (T1-w or CET1-w) model. In an independent test set of 15 patients, the DSC, sensitivity and 95% Hausdorff Distance between actual and predicted GTVr was 0.549±0.176, 0.696±0.118 and 9.813±4.788 which was superior to 0.444±0.188, 0.497±0.218 and 12.047±5.361 of original 3D U-Net. The proposed two-step radiomics workflow showed a good performance in predicting tumor recurrence of NPC. The predicted location of the recurrence lesion was all accurate, but there was still a certain difference between the volume of the automated delineated and actual GTVr, which needed to be further optimized to be used as biological tumor volume.