A Clinical-Genetic Risk Score for Predicting Cancer-Associated Venous Thromboembolism: A Development and Validation Study Involving Two Independent Prospective Cohorts.

Autor:	Muñoz A; Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain., Ay C; Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia., Grilz E; Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., López S; Genomics of Complex Diseases Unit, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain., Font C; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Hospital Clínic, Barcelona, Spain., Pachón V; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Hospital Universitario Ramón y Cajal Madrid, Madrid, Spain., Castellón V; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Complejo Hospitalario de Torrecárdenas, Almería, Spain., Martínez-Marín V; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Hospital Universitario La Paz, Madrid, Spain., Salgado M; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Complejo Hospitalario Universitario de Ourense, Ourense, Spain., Martínez E; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., Calzas J; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Hospital Universitario de Fuenlabrada, Madrid, Spain., Ortega L; Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain., Rupérez A; Cancer and Thrombosis Working Section, Spanish Society of Medical Oncology (SEOM), Madrid, Spain.; Medical Oncology, Fundación Jiménez Díaz, Madrid, Spain., Salas E; Scientific Department, Gendiag.exe, Barcelona, Spain., Pabinger I; Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Soria JM; Genomics of Complex Diseases Unit, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Jun 01; Vol. 41 (16), pp. 2911-2925. Date of Electronic Publication: 2023 Feb 02.
DOI:	10.1200/JCO.22.00255
Abstrakt:	Purpose: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis. Methods: The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population. Results: Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m 2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001). Conclusion: The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.
Databáze:	MEDLINE
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