Derivation and Validation of a Clinical Risk Assessment Model for Cancer-Associated Thrombosis in Two Unique US Health Care Systems

Authors

Ang Li
Jennifer La
Sarah B May
Danielle Guffey
Wilson L da Costa
Christopher I Amos
Raka Bandyo
Emily M Milner
Karen M Kurian
Daniel C R Chen
Nhan V Do
Carolina Granada
Nimrah Riaz
Mary T Brophy
Vipul Chitalia
J Michael Gaziano
David A Garcia
Marc Carrier
Christopher R Flowers
Neil A Zakai
Nathanael R Fillmore

Publication Date

6-1-2023

Journal

Journal of Clinical Oncology

DOI

10.1200/JCO.22.01542

PMID

36626707

PMCID

PMC10431461

PubMedCentral® Posted Date

1-10-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Venous Thromboembolism, Retrospective Studies, Prospective Studies, Venous Thrombosis, Thrombosis, Pulmonary Embolism, Neoplasms, Risk Assessment, Risk Factors, Delivery of Health Care

Abstract

PURPOSE: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy.

METHODS: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS).

RESULTS: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set.

CONCLUSION: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months (v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.