Multitask Learning Radiomics on Longitudinal Imaging to Predict Survival Outcomes following Risk-Adaptive Chemoradiation for Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Personalized cancer treatment strategies, including risk-adaptive chemoradiation therapy based on medical imaging, seek to improve outcomes of patients with unresectable and locally advanced non-small cell lung cancer. Refining patient risk stratification relies on outcome prediction modeling based in part on information from different imaging modalities and imaging time points during and after treatment. Using prospectively collected longitudinal data from FDG-PET, CT, and perfusion SPECT images of patients enrolled on a clinical trial, our aim was to evaluate the utility of a multitask machine learning radiomics framework for survival outcome prediction. We found that multitask learning of FDG-PET radiomics on pretreatment and mid-treatment images achieved higher survival prediction concordance compared with single-task learning of other modalities and clinical benchmark models. Our multitask learning radiomics framework can be applied to other longitudinal imaging datasets, and, once validated, can strengthen clinical decision support for personalized and adaptive treatment courses. ABSTRACT: Medical imaging provides quantitative and spatial information to evaluate treatment response in the management of patients with non-small cell lung cancer (NSCLC). High throughput extraction of radiomic features on these images can potentially phenotype tumors non-invasively and support risk stratification based on survival outcome prediction. The prognostic value of radiomics from different imaging modalities and time points prior to and during chemoradiation therapy of NSCLC, relative to conventional imaging biomarker or delta radiomics models, remains uncharacterized. We investigated the utility of multitask learning of multi-time point radiomic features, as opposed to single-task learning, for improving survival outcome prediction relative to conventional clinical imaging feature model benchmarks. Survival outcomes were prospectively collected for 45 patients with unresectable NSCLC enrolled on the FLARE-RT phase II trial of risk-adaptive chemoradiation and optional consolidation PD-L1 checkpoint blockade (NCT02773238). FDG-PET, CT, and perfusion SPECT imaging pretreatment and week 3 mid-treatment was performed and 110 IBSI-compliant pyradiomics shape-/intensity-/texture-based features from the metabolic tumor volume were extracted. Outcome modeling consisted of a fused Laplacian sparse group LASSO with component-wise gradient boosting survival regression in a multitask learning framework. Testing performance under stratified 10-fold cross-validation was evaluated for multitask learning radiomics of different imaging modalities and time points. Multitask learning models were benchmarked against conventional clinical imaging and delta radiomics models and evaluated with the concordance index (c-index) and index of prediction accuracy (IPA). FDG-PET radiomics had higher prognostic value for overall survival in test folds (c-index 0.71 [0.67, 0.75]) than CT radiomics (c-index 0.64 [0.60, 0.71]) or perfusion SPECT radiomics (c-index 0.60 [0.57, 0.63]). Multitask learning of pre-/mid-treatment FDG-PET radiomics (c-index 0.71 [0.67, 0.75]) outperformed benchmark clinical imaging (c-index 0.65 [0.59, 0.71]) and FDG-PET delta radiomics (c-index 0.52 [0.48, 0.58]) models. Similarly, the IPA for multitask learning FDG-PET radiomics (30%) was higher than clinical imaging (26%) and delta radiomics (15%) models. Radiomics models performed consistently under different voxel resampling conditions. Multitask learning radiomics for outcome modeling provides a clinical decision support platform that leverages longitudinal imaging information. This framework can reveal the relative importance of different imaging modalities and time points when designing risk-adaptive cancer treatment strategies.