1484O - Deep learning predicts patients’ outcome and mutations from H&E slides in gastrointestinal stromal tumor (GIST)

Background

Risk assessment according to the AFIP/Miettinen classification and mutational profiling are major tools for patient management. However, the AFIP/Miettinen classification depends heavily on mitotic counts, which is laborious and sometimes inconsistent between pathologists. It has also been shown to be imperfect in stratifying patients. Molecular testing is costly and time consuming, therefore not systematically performed in all countries. New methods to improve risk and molecular predictions are hence crucial to improve the tailoring of adjuvant therapy.

Methods

We have built deep learning (DL) models on digitized H&E-stained whole slide images (WSI) to predict patients’ outcome and mutations. Models were trained with a cohort of 1233 GIST and validated on an independent cohort of 286 GIST.

Results

DL models outperformed the Miettinen classification for relapse-free-survival prediction in localized GIST without adjuvant Imatinib (C-index=0.83 in testing and 0.72 for independent validation). DL splitted Miettinen intermediate risk GIST into high/low risk groups(p value=2.1e-03). DL models achieved an area under the receiver operating characteristic curve (AUC) of 0.81, 0.91 and 0.71 for predicting mutations in KIT, PDGFRA and wild type respectively in testing and 0.84, 0.93 and 0.56 in independent validation. Notably, PDGFRA exon18 D842V mutation which is resistant to Imatinib, was predicted with an AUC of 0.87 and 0.90 in testing and independent validation, respectively. Additionally, novel histological criteria predictive of patients’ outcome and mutations were identified by reviewing the tiles selected by the models.

Conclusions

Our results strongly suggest that implementing DL with digitized WSI may represent a reproducible way to improve tailoring therapy and precision medicine for patients with GIST.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Institut Bergonié. Bordeaux, France.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.