Ct-based subregional radiomics using hand-crafted and deep learning features for prediction of therapeutic response to anti-PD1 therapy in NSCLC

Purpose: To develop and externally validate subregional radiomics for predicting therapeutic response to anti-PD1 therapy in non-small-cell lung cancer (NSCLC). Methods: Sixty-six patients from center 1 served as training and internal validation cohorts. Thirty patients from center 2 and thirty patients from center 3 served as external validation 1 and external validation 2 cohorts, respectively. The lesions identified on CT scans were subdivided into two phenotypically consistent subregions by automatic clustering on the patient-level and population-level (denoted as marginal S1 and inner S2). Handcrafted and deep learning-based features were extracted separately from the entire tumor region and subregions, then selected using the intraclass correlation coefficient and least absolute shrinkage and selection operator regression (LASSO). Radiomics signatures (RSs) were built integrating the selected features and correlation coefficients using a logistic regression method. Area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the RSs. Results: RSs derived from S1 outperformed those from S2 and the whole tumor region for both handcrafted and deep learning features. The Fusion-RS incorporating the two feature types achieved the best prediction performance in training (AUC = 0.947, 95 % Confidence Interval [CI] 0.905-0.989, SPE = 0.895, SEN = 0.878), internal validation (AUC = 0.875, 95 % CI: 0.782-0.969, SPE = 0.724, SEN = 0.952), external validation 1 (AUC = 0.836, 95 % CI: 0.694-0.977, SPE = 1.000, SEN = 0.533) and external validation 2 (AUC = 0.783, 95 % CI: 0.613-0.953, SPE = 0.765, SEN = 0.692) cohorts. Conclusions: Subregional radiomics analysis can be useful for predicting therapeutic response to anti-PD1 therapy. The developed Fusion-RS may be considered as a potential non-invasive tool for individual treatment managements.