Multi-block Discriminant Analysis of Integrative 18F-FDG-PET/CT Radiomics for Predicting Circulating Tumor Cells in Early Stage Non-small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

Abstract Purpose To integrate 18F-FDG-PET/CT radiomics with multi-block discriminant analysis for predicting circulating tumor cells (CTCs) in early stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods Fifty-six patients with stage I NSCLC treated with SBRT underwent 18F-FDG-PET/CT imaging pre-SBRT and post-SBRT (median, 5 months; range, 3-10 months). CTCs were assessed via a telomerase-based assay before and within 3 months after SBRT and dichotomized at 5 and 1.3 CTCs/mL. Pre-SBRT, post-SBRT and delta PET/CT radiomics features (n=1,548×3/1,562×3) were extracted from gross tumor volume. Seven feature blocks were constructed including clinical parameters (n=12). Multi-block data integration was performed using block sparse partial least squares-discriminant analysis (sPLS-DA) referred as DIABLO for identifying key signatures by maximizing common information between different feature blocks, while discriminating CTC levels. Optimal input blocks were identified using a pairwise combination method. DIABLO performance for predicting pre-SBRT and post-SBRT CTCs was evaluated using combined AUC (area under the curve, averaged across different blocks) analysis with 20×5-fold cross-validation (CV), and compared with that of concatenation-based sPLS-DA that consisted of combining all features into one block. CV prediction scores between one class vs the other were compared using the Wilcoxon rank sum test. Results For predicting pre-SBRT CTCs, DIABLO achieved the best performance with combined pre-SBRT PET radiomics and clinical feature blocks, showing CV-AUC of 0.875 (p=0.009). For predicting post-SBRT CTCs, DIABLO achieved the best performance with combined post-SBRT CT and delta CT radiomics feature blocks, showing CV-AUCs of 0.883 (p=0.001). In contrast, all single-block sPLS-DA models could not attain CV-AUCs higher than 0.7. Conclusions Multi-block integration with discriminant analysis of 18F-FDG-PET/CT radiomics has the potential for predicting pre-SBRT and post-SBRT CTCs. Radiomics and CTC analysis may complement and together help guide the subsequent management of patients with ES-NSCLC.