Deep Learning of Histopathology Predicts Outcomes After Surgery for Pancreatic Cancer.
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Wong Avelyn, Bourega Taib A, Nicolle Rémy, Elqaderi Ayah, Nowak Klaudia M, Light Nicholas, Wang Xin, Quan Wei, Ji Zongliang, Abbas-Aghababazadeh Farnoosh, Henault David, He Jiang Chen, Chen Zejia, Hutchinson Shawn, Dodd Anna, Wilson Julie, Jang Gun Ho, Biankin Andrew, Chang David, O'Callaghan Christopher J, Biagi James, Canadian Cancer Trials Group, Conroy Thierry, Hammel Pascal, Unicancer-GI–PRODIGE Group, Notta Faiyaz, Knox Jennifer J, Gallinger Steven, Krishnan Rahul G, Cros Jerome, Grant Robert C
Аннотация
METHODS: Publicly available WSI of pancreatic ductal adenocarcinoma resections from three cohorts were used for training. The model consisted of a pan-cancer foundation model to generate embeddings, mean-pooling across tissue patches, and then a fully connected neural network. Model predictions were compared with human-labeled histopathologic features and genomic alterations. The model was externally validated in a meta-analysis of a single-center cohort from Princess Margaret Cancer Centre, a multicenter cohort from France, and the PRODIGE 24 trial of adjuvant chemotherapy.
RESULTS: The deep learning model was trained on 12,594 tissue patches from 257 patients. High-risk classifications were associated with squamous morphology, reactive stroma, tumor cellularity, and necrosis, whereas low-risk classifications were associated with tubulopapillary and conventional morphologies, as well as deserted stroma. High-risk cancers were enriched for basal-like gene expression profiles and distinct oncogenic pathways. In a meta-analysis of the external cohorts, the hazard ratio (HR) for death comparing high-versus low-risk cancers was 1.49 (95% CI, 1.25 to 1.79, P < .001), whereas the HR for recurrence or death was 1.41 (95% CI, 1.19 to 1.68, P < .001). The classifications remained prognostic among moderately differentiated cancers.
CONCLUSION: An open-source deep learning model using WSI from pancreatic cancer resections generated risk classifications that correlated with histopathologic and genomic features. Classifications were externally validated in a meta-analysis of three cohorts. This model could be applied to WSI to provide individualized prognostic information for patients.