Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

Abstract

BackgroundVenous thromboembolism (VTE) is a leading cause of death among patients with cancer. Outpatients with cancer should be periodically assessed for VTE risk, for which the Khorana score is commonly recommended. However, it has been questioned whether this tool is sufficiently accurate at identifying patients who should receive thromboprophylaxis. The present work proposes a new index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer, that examines patients’ clinical and genetic risk factors for thrombosis.MethodsWe included 391 outpatients with a recent diagnosis of cancer and candidates for systemic outpatient chemotherapy. All were treated according to standard guidelines. The study population was monitored for 6 months, and VTEs were recorded. The Khorana and the TiC-Onco scores were calculated for each patient and their VTE predictive accuracy VTEs was compared.ResultsWe recorded 71 VTEs. The TiC-Onco risk score was significantly better at predicting VTE than the Khorana score (AUC 0.73 vs. 0.58, sensitivity 49 vs. 22%, specificity 81 vs. 82%, PPV 37 vs. 22%, and NPV 88 vs. 82%).ConclusionsTiC-Onco risk score performed significantly better than Khorana score at identifying cancer patients at high risk of VTE who would benefit from personalised thromboprophylaxis.

SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019)

“…Khorana score was the first validated risk assessment model (RAM) for identifying VTE high-risk patients receiving chemotherapy. After this publication, different RAM have been published and some of them have been validated (Table 3) [24][25][26][27][28][29][30][31][32]. Other RAM addressed to specific tumors such as THROLY [33] or testicular germ cell tumors [34].…”

“…It is recommended to use a validated RAM to assess VTE risk (level of evidence: grade 2C). Vienna CATS score [25] PROTECHT score [26] CONKO score [27] Oncothromb-Tic Onco score extended [28,29] Compass-CAT score [30]…”

“…Compared to LMWH or UFH, fondaparinux was not statistically different in all endpoints including mortality, recurrence VTE, and bleeding. In the second meta-analysis [53], a subgroup analysis of cancer patients Vienna CATS score [25] PROTECHT score [26] CONKO score [27] Oncothromb-Tic Onco score extended [28,29] Compass-CAT score [30] a Onkotev score [31] Pabinger et al [32] Tumor vascular/ lymphatic compression reported a significant reduction in mortality with LMWH compared to UFH (OR 0.53, 95% CI 0.33-0.85; p = 0.009).…”

Risk factors for cancer‐associated venous thromboembolism: The venous thromboembolism prevention in the ambulatory cancer clinic (VTE‐PACC) study

“…4 Many professional organizations and researchers have concerns about whether these scores are accurate enough to make recommendations on prescribing VTE prophylaxis. [5][6][7] The Khorana Score was developed using data from an observational study of outpatient cancer patients initiating chemotherapy, and stratifies these patients into high, intermediate, and low risk of developing VTE during the subsequent 6 months. 8 This score includes tumor type, body mass index (BMI), and pre-chemotherapy hemoglobin, white blood cell, and platelet counts.…”

Cancer‐associated thrombosis: The search for the holy grail continues

“…The most recently developed risk score, TiC-Onco-that also includes genetic risk factors-showed a positive predictive value of up to 37%, which is only an incremental increase over the predictive values obtained after using the Khorana score that correctly predicted VTE in only 22% of the CAT patients. 15 The main reason why progress in understanding and predicting CAT is slow is the fact that many investigators extrapolate classical VTE risk factors to CAT patients, with addition of a few extra risk factors related to cancer. However, a recent publication indicates that cancer patients with VTE have different plasma profiles compared to patients with VTE only.…”