Testing biomarkers in NSCLC relies on complex sequencing and imaging techniques, leading to financial and operational challenges for health care systems. As such, some testings are not systematically performed, while specific targeted therapies exist for those biomarkers. With a prevalence of 13% in NSCLC patients with lung adenocarcinoma, KRAS G12C mutation is considered among the most essential ones. This study aims at showing that AI techniques applied to digital pathology could offer a fast and cheap mass patient screening solution to complement DNA testing by predicting the KRAS mutation status and its G12C subtype from digital pathology slides used in clinical workflow.
For that purpose, data from 1,076 non-small cell carcinoma patients from Institut Bergonie and partner centers was used to train a DeepMIL deep learning model. For each patient, H&E diagnostic slides from resections or biopsies, as well as the KRAS mutation status and G12C subtype obtained with NGS have been used to run analyses and train models. The model was evaluated through a repeated cross validation scheme on the local cohort, and later evaluated on the TCGA-LUAD public cohort (537 patients).
Our deep learning models succeed in discriminating KRAS G12C mutated patients from wild type or other subtype by using routine H&E histology data with encouraging performance range of 58% (P=.04) and 65% (average of the cross-validated performances) ROC AUC obtained respectively on public and local cohorts. Furthermore, a systematic analysis performed with an experienced pathologist revealed that the regions of interest associated with the G12C status identified by the model contained a significant over-representation of tumoral cells. While requiring further work to reveal its full potential, this experimentation is the first demonstrating that KRAS G12C mutated patient identification would be possible through morphological patterns analysis from annotation-free whole slide imaging.
In future, these innovative approaches could complete existing testing techniques and pave the way for a more systematic, early and potentially cost-effective mass screening approach of KRAS G12C mutations in clinical routine.
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R. Dubois, A. Jaeger, J. Moreira: Financial Interests, Personal, Full or part-time Employment: Owkin. Inc. B. Allard, A. Rousset: Financial Interests, Personal, Full or part-time Employment: Amgen. All other authors have declared no conflicts of interest.