Multimodal Integration of Longitudinal Noninvasive Diagnostics for Survival Prediction in Immunotherapy Using Deep Learning

Purpose: Analyzing noninvasive longitudinal and multimodal data using artificial intelligence could potentially transform immunotherapy for cancer patients, paving the way towards precision medicine. Methods: In this study, we integrated pre- and on-treatment blood measurements, prescribed medications and CT-based volumes of organs from a large pan-cancer cohort of 694 patients treated with immunotherapy to predict short and long-term overall survival. By leveraging a combination of recent developments, different variants of our extended multimodal transformer-based simple temporal attention (MMTSimTA) network were trained end-to-end to predict mortality at three, six, nine and twelve months. These models were also compared to baseline methods incorporating intermediate and late fusion based integration methods. Results: The strongest prognostic performance was demonstrated using the extended transformer-based multimodal model with area under the curves (AUCs) of $0.84 \pm $0.04, $0.83 \pm $0.02, $0.82 \pm $0.02, $0.81 \pm $0.03 for 3-, 6-, 9-, and 12-month survival prediction, respectively. Conclusion: Our findings suggest that analyzing integrated early treatment data has potential for predicting survival of immunotherapy patients. Integrating complementary noninvasive modalities into a jointly trained model, using our extended transformer-based architecture, demonstrated an improved multimodal prognostic performance, especially in short term survival prediction.

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.