Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer

Abstract

ImportanceThe assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event.ObjectiveTo validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer.Design, Setting, and ParticipantsONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019.ExposuresThe ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period.Main Outcomes and MeasuresThe primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism.ResultsA total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively.Conclusions and RelevanceThis study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.

Decision curve analysis based on summary data

“…The mean/SD summary estimates from the Cox prediction model were 0.479/0.253. We performed DCA/gDCA using ONKOTEV model ( n = 425) to assess its use as primary thromboprophylaxis in patients treated for cancer in the ambulatory setting 28 . The ONKOTEV employed competing‐risk time‐to‐event regression .…”

“…We performed DCA/gDCA using ONKOTEV model (n = 425) to assess its use as primary thromboprophylaxis in patients treated for cancer in the ambulatory setting. 28 The ONKOTEV employed competing-risk time-to-event regression. Harell's C discrimination statistics was 0.71 for ONKOTEV with good calibration properties (with intercept and the slope not statistically significantly different from 0 to 1, respectively).…”

Novel Insights in Venous Thromboembolism Risk Assessment Methods in Ambulatory Cancer Patients: From the Guidelines to Clinical Practice

“…In their prospective study, the area under the curve of ONKOTEV over the Khorana score was reported at 3 months (71.9% vs. 57.9%, p = 0.001), 6 months (75.4% vs. 58.6%, p < 0.001), and 12 months (69.8% vs. 58.3%, p = 0.014) [67]. Cella et al (2023) validated this model in the ONKOTEV-2, a multicenter prognostic study on ambulatory patients with solid tumors undergoing active treatments [68]. The most represented tumors were breast (18.1%), gastroesophageal adenocarcinoma (16.5%), colon (12.7%), lung (11.1%), rectum (10.8%), and pancreatic cancers (7.5%) [68].…”

“…Cella et al (2023) validated this model in the ONKOTEV-2, a multicenter prognostic study on ambulatory patients with solid tumors undergoing active treatments [68]. The most represented tumors were breast (18.1%), gastroesophageal adenocarcinoma (16.5%), colon (12.7%), lung (11.1%), rectum (10.8%), and pancreatic cancers (7.5%) [68]. Di Nisio et al reported that the performance of the Khorana, PROTECHT, CONKO, and ONKOTEV scores improved at the threshold of 2 points, compared to 3 points [49].…”

In Search of the Perfect Thrombosis and Bleeding-Associated Cancer Scale

“…18 24 Furthermore, the ONKOTEV score, consisting of four variables: a Khorana score greater than 2, metastatic disease, vascular or lymphatic compression, and a prior history of VTE, was designed for ambulatory oncologic patients. 18 25 In the Tic-Onco risk score, clinical factors were incorporated in addition to a genetic risk score based on identified single nucleotide polymorphism risk alleles. 6 Another helpful model is the COMPASS-CT score, which includes various clinical characteristics and comorbidities, such as cardiovascular risk factors, treatment types (e.g., antihormonal therapy in hormone receptor-positive breast cancer), and platelet counts.…”