Machine learning-based multimodal prognostic models integrating pathology images and high-throughput omic data for overall survival prediction in cancer: a systematic review

Multimodal machine learning integrating histopathology and molecular data shows promise for cancer prognostication. We systematically reviewed studies combining whole slide images (WSIs) and high-throughput omics to predict overall survival. Searches of EMBASE, PubMed, and Cochrane CENTRAL (12/08/2024), plus citation screening, identified eligible studies. Data extraction used CHARMS; bias was assessed with PROBAST+AI; synthesis followed SWiM and PRISMA 2020. Protocol: PROSPERO (CRD42024594745). Forty-eight studies (all since 2017) across 19 cancer types met criteria; all used The Cancer Genome Atlas. Approaches included regularised Cox regression (n=4), classical ML (n=13), and deep learning (n=31). Reported c-indices ranged 0.550-0.857; multimodal models typically outperformed unimodal ones. However, all studies showed unclear/high bias, limited external validation, and little focus on clinical utility. Multimodal WSI-omics survival prediction is a fast-growing field with promising results but needs improved methodological rigor, broader datasets, and clinical evaluation. Funded by NPIC, Leeds Teaching Hospitals NHS Trust, UK (Project 104687), supported by UKRI Industrial Strategy Challenge Fund.

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance.