Abstract

Simple SummaryPersonalized 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.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.

Highlights

  • Cancer mortality and incidence remains significant with aging and population growth amid a multitude of risk factors, wherein lung cancer features high mortality and incidence rates [1]

  • Our aim was to evaluate whether multitask learning of pretreatment and mid-treatment radiomic features can improve survival outcome prediction relative to benchmark models consisting of clinical imaging features or delta radiomics

  • The framework was applied to survival outcome modeling in a cohort of patients with unresectable non-small cell lung cancer enrolled on the FLARE-RT phase II clinical trial, from which computed tomography (CT), FDG-positron emission tomography (PET), and perfusion single-photon emission computerized tomography (SPECT) radiomic features at pre- and mid-treatment time points were extracted

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Summary

Introduction

Cancer mortality and incidence remains significant with aging and population growth amid a multitude of risk factors, wherein lung cancer features high mortality and incidence rates [1]. Despite recent advances in treatment strategies, including combinations of surgery, chemotherapy, immunotherapy, and radiation therapy, median overall survival for patients with non-small cell lung cancer (NSCLC) remains poor and not all patients derive similar benefit This highlights the importance of discovering and validating biomarkers that are both sensitive to treatment effects and predict outcomes following combination cancer therapies [2], enabling patient risk stratification for individualized treatment techniques. Biomarkers from quantitative medical imaging, such as positron emission tomography (PET), computed tomography (CT), and single-photon emission computerized tomography (SPECT), have been used to assess various components of cancer treatment response or risk of treatment-related side effects [21–23] Among these imaging modalities, fluorodeoxyglucose (FDG)-PET/CT has been applied for quantitative assessment of early tumor response to lung cancer therapy and predicting survival outcomes [24]. The aforementioned studies were restricted to single imaging modalities—which may neglect information content from other modalities [10,14,15,32]—or required large data sets to train deep learning models, which may not be appropriate for smaller available data sets in early phase clinical trial settings [11,33]

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