denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 803. Emerging Tools, Techniques, and Artificial Intelligence in Hematology: Poster II
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, MDS, Artificial intelligence (AI), Adult, Translational Research, MPN, Elderly, Clinical Research, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Myeloid Malignancies, Biological Processes, Emerging technologies, Technology and Procedures, Multi-systemic interactions, Study Population, Human, Imaging, Machine learning, Omics technologies, Pathology
AIMS. This project was conducted by the GenoMed4All and Synthema consortia, to build AI-based features extraction tools from BM histopathological and cytological Whole Slide Images (WSI). High-dimensional data were used to 1) assess diagnostic accuracy in MN patients; 2) elucidate the association between morphologic features, clinical variables and molecular genetics, and 3) create an innovative tool for personalized risk assessments integrating morphological features with clinical and genomic information.
METHODS. The study population included 1167 MN patients(18% AML; 44% MDS, 29% MPN, 9% MDS/MPN) from Humanitas Research Hospital, with available demographic, clinical, cytogenetic and genomic data, alongside with treatments, outcomes information and WSI collected from BM aspiration and biopsy at different timepoints during disease history. AI-based features extraction models were developed for different staining (May-Grunwald Giemsa (MGG), Perls, Hematoxylin-Eosin, Gomori, CD34, MPO, CD117, CD71, CD61, CD20, CD3, and P53). Different models and training strategies were employed to segment structures in each staining, like nuclei, cells and fibrosis; morphological and textural features were then extracted. Hematologists and hemato-pathologists feedback was included in the training process. Moreover, a classification model was developed to analyze cells on MGG smears, predicting 12 different cell types. The percentages of markers, cell types, and tissue components, combined with their spatial organization, were integrated to address the clinical aims of the project. Explainability and interpretability were implemented by SHapley Additive exPlanations approach (SHAP).
RESULTS. Multiple Gradient Boosting binary classifiers were trained using the WSI features to discriminate specific clinical entities among MN. The models predicted a correct diagnosis with an F1 Score > 90%, suggesting that extracted features capture clinically relevant information. MDS/MPN phenotype cases resulted in the most diagnostic disagreement between AI-models and pathologists.
Then we analysed the morphologic and molecular features association. Specific genomic profiles were predicted from WSI features with specialized XGBOOST models with high accuracy, in particular for SF3B1, JAK/STAT, TP53 and RUNX1 mutations (all with F1 Score > 90%).
These findings underline the capability of the morphological features to capture the biological background of MN.
On these bases, we integrated morphological features into an innovative prognostic tool for personalized prediction of overall survival (OS) and leukemia-free survival (LFS) in MN. After the feature selection process (by using a L1-penalized Cox regression) 71 morphological features were included in the model together with demographic, clinical and genomic information. Model discrimination was assessed using Harrell’s concordance index (CI).
Sequential integration of data layers into the model showed an increasing CI for OS and LFS, starting with 0.68 and 0.59, respectively with clinical and cytogenetic features alone; then raising CI up to 0.75 and 0.64 including somatic gene mutations; and finally reaching CI of 0.87 and 0.85 further integrating morphological features.
Validation is currently ongoing on an independent MN population from MD Anderson Cancer Center, US.
CONCLUSION. Our developed AI models were capable of automatically extract textural, cell features and markers from WSI. The morphological features integration significantly improved personalized patient stratification and prognostication in MN. The proposed solution provided a fully explainable interpretation of high dimensional features, thus facilitating a wide clinical implementation.
Disclosures: Santoro: Novartis: Speakers Bureau; Beigene: Speakers Bureau; Sandoz: Speakers Bureau; Lilly: Speakers Bureau; Arqule: Speakers Bureau; Astrazeneca: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Abb-vie: Speakers Bureau; Roche: Speakers Bureau; Takeda: Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EISAI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy; Sanofi: Consultancy. Santini: Ascentage, AbbVie, Bristol Myers Squibb, CTI BioPharma, Geron, Gilead, Novartis, Servier, Syros Pharmaceuticals: Other: Advisory Board. Platzbecker: Merck: Research Funding; Amgen: Consultancy, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Curis: Consultancy, Honoraria, Research Funding; Geron: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding. Fenaux: Agios: Research Funding; BMS: Honoraria, Research Funding; Novartis: Research Funding; Janssen: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Astex: Research Funding; Servier: Research Funding; AbbVie: Honoraria, Research Funding. Diez-Campelo: BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees; ASTEX/OTSUKA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL TO MEETINGS; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees; BLUEPRINT MEDICINES: Consultancy, Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; CURIS: Membership on an entity's Board of Directors or advisory committees; SYROS: Membership on an entity's Board of Directors or advisory committees; HEMAVAN: Membership on an entity's Board of Directors or advisory committees; Gilead: Other: Travel reimbursement. Komrokji: Janssen: Consultancy; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Honoraria; Servio: Membership on an entity's Board of Directors or advisory committees; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Taiho: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kordasti: API: Consultancy; Alexion: Consultancy; Beckman Coulter: Speakers Bureau; MorphoSys: Research Funding; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Research Funding; Boston Biomed: Consultancy. Loghavi: Pathology Education Partners; VJ HemeOnc, College of American Pathologists, OncLive, ICCS, MD Education, NCCN, MashUp Media, NCTN, Aptitude Health: Honoraria; Guidepoint; QualWorld; Gerson Lehrman Group, AlphaSight, Arima, Qiagen, Opinion Health: Consultancy; Astellas, Amgen: Research Funding; Abbvie: Current holder of stock options in a privately-held company; Syndx, Servier, BMS: Membership on an entity's Board of Directors or advisory committees; Abbvie, Daiichi Sankyo, BluePrint Medicine, Caris Diagnostics, Recordati, Servier: Consultancy. Garcia-Manero: Curis: Research Funding; Janssen: Research Funding; Onconova: Research Funding; Astex: Other: Personal fees; Genentech: Research Funding; Helsinn: Other: Personal fees; AbbVie: Research Funding; Bristol Myers Squibb: Other: Personal fees, Research Funding; Astex: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Genentech: Other: Personal fees; Forty Seven: Research Funding; Helsinn: Research Funding; Novartis: Research Funding; Aprea: Research Funding; Amphivena: Research Funding. Della Porta: Bristol Myers Squibb: Consultancy.