Abstract
Venous thromboembolism (VTE) is common in patients with cancer and is an important contributor to morbidity and mortality in these patients. Early thromboprophylaxis initiated only in those cancer patients at highest risk for VTE would be optimal. Risk stratification scores incorporating tumor location, laboratory values and patient characteristics have attempted to identify those patients most likely to benefit from thromboprophylaxis but even well-validated scores are not able to reliably distinguish the highest-risk patients. Recognizing that tumor genetics affect the biology and behavior of malignancies, recent studies have explored the impact of specific molecular aberrations on the rate of VTE in cancer patients. The presence of certain molecular aberrations in a variety of different cancers, including lung, colon, brain and hematologic tumors, have been associated with an increased risk of VTE and arterial thrombotic events. This review examines the findings of these studies and discusses the implications of these findings on decisions relating to thromboprophylaxis use in the clinical setting. Ultimately, the integration of tumor molecular genomic information into clinical VTE risk stratification scores in cancer patients may prove to be a major advancement in the prevention of cancer-associated thrombosis.
Highlights
Thrombotic complications, in particular venous thromboembolism (VTE), are common in patients with cancer where they are a major cause of morbidity and mortality [1]
In the case of molecular aberrations in other tumors (Table 2), knowledge that a patient may be at increased thrombotic risk due to their underlying tumor genotype is another piece of information that the treating clinician can consider when determining if a patient may be likely to benefit from thromboprophylaxis, along with traditional thrombotic risk factors such as elevated body mass index (BMI), previous VTE and known hereditary thrombophilia
Thrombosis greatly contributes to morbidity and mortality in cancer patients
Summary
Thrombotic complications, in particular venous thromboembolism (VTE), are common in patients with cancer where they are a major cause of morbidity and mortality [1]. In the on-treatment analysis, rivaroxaban did significantly reduce thrombotic events compared to placebo (2.6% vs 6.4% with a hazard ratio of 0.40) While these trials represent an improvement over the unselected population evaluated in the prior LMWH trials, the overall NNT to prevent one VTE using a Khorana score of 2 or higher and low-dose DOAC therapy was approximately 20–25, with a NNH to cause a major bleed of approximately 75 [26]. These findings suggest that use of the Khorana risk score to guide thromboprophylaxis as was done in AVERT and CASSINI offers a clear tradeoff: prevent three VTE events for every major bleed caused by thromboprophylaxis. Even with the use of the best-validated existing risk-prediction model, optimal patient selection for primary thromboprophylaxis remains challenging
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