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Personalized Cancer-associated Thrombosis Risk Assessment: Integration of Plasma Proteomics, Clinical Characteristics, and Machine Learning

J. Zwicker1, E. Elango1, R. Patell1, M. Marchetti2, L. Russo2, C. Verzeroli2, C. Giaccherini2, S. Gamba2, R. Flaumenhaft1, C.J Tartari2, I. Vlachos1, A. Falanga2,3

1Beth Israel Deaconess Medical Center, Boston, United States, 2ASST Papa Giovanni XXIII, Bergamo, Italy, 3University of Milan Bicocca, Milan, Italy

Abstract Number: OC 23.1

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Cancer Associated Thrombosis

Background: Accurate risk assessment cancer associated thrombosis (CAT) can inform optimal patient selection for thromboprophylaxis.  Unfortunately, a uniform biomarker does not exist and the current risk scoring methods exhibit modest accuracy. Machine learning can capture rich multi-dimensional patient information and identify patients at increased risk for CAT.

Aims: We aimed to identify a novel set of variables predictive of CAT using machine learning to analyze a comprehensive feature space combining proteomic and clinical features in a well-curated prospective cancer cohort.

Methods: A proximity extension assay was used to quantify 1,161 proteins in 183 gastric and lung cancer patients enrolled in the HYPERCAN Study (ClinicalTrials.gov #NCT02622815). Samples were collected at time of cancer diagnosis and patients were prospectively followed for the development of CAT. Machine learning predictive models were built using plasma protein concentrations and clinical/laboratory information from the accompanying patient metadata (>300 variables). The derived machine learning models were compared to Khorana Score to predict venous thromboembolism (VTE).  

Results: Of the total cohort of 183 cancer patients, 103 had gastric cancer and 80 lung cancer, and 58% had metastasis at baseline. Median age was 64 years and 32% were female. Approximately one-third (32%) of patients in the cohort developed a thrombotic event on follow-up. A machine learning driven model identified 10 plasma proteins and 6 clinical features predictive of thrombosis. The algorithm predicted VTE with high accuracy (AUC 0.75+0.04)). By comparison, the Khorana Score was not predictive of VTE (AUC 0.52). (Figure 1).

Receiver Operating Characteristics analysis of machine learning driven model combining 10 plasma proteins and 6 clinical features to predict venous thrombosis in patients with active cancer. 

Conclusions: This study supports utilizing machine learning in conjunction with novel biomarker discovery for the creation of a next generation high accuracy CAT predictive modeling. Validation of prediction model is ongoing.

To cite this abstract in AMA style:

Zwicker J, Elango E, Patell R, Marchetti M, Russo L, Verzeroli C, Giaccherini C, Gamba S, Flaumenhaft R, J Tartari C, Vlachos I, Falanga A. Personalized Cancer-associated Thrombosis Risk Assessment: Integration of Plasma Proteomics, Clinical Characteristics, and Machine Learning [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/personalized-cancer-associated-thrombosis-risk-assessment-integration-of-plasma-proteomics-clinical-characteristics-and-machine-learning/. Accessed September 22, 2023.

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