Assessing risk of venous thromboembolism in the patient with cancer.
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ABSTRACT:
SUBMITTER: Khorana AA
PROVIDER: S-EPMC2764392 | biostudies-literature | 2009 Oct
REPOSITORIES: biostudies-literature
Publications
Assessing risk of venous thromboembolism in the patient with cancer.
Khorana Alok A AA Connolly Gregory C GC
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20090831 29
<h4>Purpose</h4>Patients with cancer are increasingly at risk for venous thromboembolism (VTE). Rates of VTE, however, vary markedly among patients with cancer.<h4>Design</h4>This review focuses on recent data derived from population-based, hospital-based, and outpatient cohort studies of patients with cancer that have identified multiple clinical risk factors as well as candidate laboratory biomarkers predictive of VTE.<h4>Results</h4>Clinical risk factors for cancer-associated VTE include prim ...[more]
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Project description:Risk factors for cancer-associated thrombosis are commonly divided into three categories: patient-, cancer-, and treatment-related factors. Currently, different types of drugs are used in cancer treatment. Chemotherapy has been identified as an independent risk factor for venous thromboembolism (VTE). However, it should be noted, that the risk of VTE is not consistent among all cytotoxic agents. In addition, different supportive care drugs, such as erythropoiesis stimulating agents or granulocyte colony stimulating factors, and hormonotherapy have been associated to an increased risk of VTE. Immunotherapy and molecular-targeted therapies have significantly changed the treatment of cancer over the past decade. The main subtypes include tyrosine-kinase inhibitors, monoclonal antibodies, small molecules, and immunomodulatory agents. The relationship between VTE and targeted therapies remains largely unknown.
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Project description:BackgroundGenetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL-rs6025 and prothrombin gene PT-rs1799963. To this end, we have designed a new genetic risk score called Thrombo inCode (TiC).Methods and resultsTiC was evaluated in terms of discrimination (Δ of the area under the receiver operating characteristic curve) and reclassification (integrated discrimination improvement and net reclassification improvement). This evaluation was performed using 2 age- and sex-matched case-control populations: SANTPAU (248 cases, 249 controls) and the Marseille Thrombosis Association study (MARTHA; 477 cases, 477 controls). TiC was compared with other literature-based genetic risk scores. TiC including F5 rs6025/rs118203906/rs118203905, F2 rs1799963, F12 rs1801020, F13 rs5985, SERPINC1 rs121909548, and SERPINA10 rs2232698 plus the A1 blood group (rs8176719, rs7853989, rs8176743, rs8176750) improved the area under the curve compared with a model based only on F5-rs6025 and F2-rs1799963 in SANTPAU (0.677 versus 0.575, P<0.001) and MARTHA (0.605 versus 0.576, P=0.008). TiC showed good integrated discrimination improvement of 5.49 (P<0.001) for SANTPAU and 0.96 (P=0.045) for MARTHA. Among the genetic risk scores evaluated, the proportion of VTE risk variance explained by TiC was the highest.ConclusionsWe conclude that TiC greatly improves prediction of VTE risk compared with other genetic risk scores. TiC should improve prevention, diagnosis, and treatment of VTE.
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Project description:Background:Clinical practice shows that venous thromboembolism (VTE) presents a substantial burden in medical patients, and awareness and advocacy for its primary and secondary prevention remains inadequate. Specific patient populations, such as those with cancer and the critically ill, show elevated risk for VTE, bleeding or both, and significant gaps in VTE prophylaxis and treatment exist in these groups. Objective:To present novel insights and consolidated evidence collected from experts, clinical practice guidelines and original studies on the unmet needs in thromboprophylaxis, and on the treatment of VTE in two high-risk patient groups: patients with cancer and the critically ill. Methodology:To identify specific unmet needs in the management of VTE, a methodology was designed and implemented that assessed gaps in prophylaxis and treatment of VTE through interviews with 44 experts in the field of thrombosis and haemostasis, and through a review of current guidelines and seminal studies to substantiate the insights provided by the experts. The research findings were then analysed, discussed and consolidated by a multidisciplinary group of experts. Results:The gap analysis methodology identified shortcomings in the VTE risk assessment tools, patient stratification approaches for prophylaxis, and the suboptimal use of anticoagulants for primary prophylaxis and treatment. Conclusions:Specifically, patients with cancer need better VTE risk assessment tools to tailor primary thromboprophylaxis to tumour types and disease stages, and the potential for drug-drug interactions needs to be considered. In critically ill patients, unfractionated heparin is not advised as a first-line treatment option, and the strength of evidence is increasing for direct oral anticoagulants as a treatment option over low-molecular-weight heparins.
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Project description:BackgroundAlthough the Khorana venous thromboembolism (VTE) risk score (KRS) is well recognized as a simple VTE risk assessment method in patients with cancer, whether it is suitable for Asian populations is unclear.ObjectivesThis study validated KRS for the prediction of VTE and investigated the value of the KRS in predicting mortality in Japanese patients with cancer.MethodsA body mass index value of 25 kg/m2 or more was defined as obesity according to World Health Organization consensus. A total of 27,687 patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups by the KRS. The primary and secondary endpoints were VTE and all-cause mortality, respectively.ResultsThe prevalence of VTE was 1.7%, 7.3%, and 11.0% for low-, intermediate-, and high-score patients, respectively. Receiver operating characteristic (ROC) analysis showed that the KRS significantly predicted VTE (area under the curve, 0.679; 95% confidence interval [CI] 0.666-0.692; P < 0.001). The cutoff value for the KRS was 1.0. Logistic regression analysis demonstrated that the KRS was an independent predictor of VTE (odds ratio 1.766; 95% CI 1.673-1.865; P < 0.01). The cutoff value of the KRS for all-cause mortality determined by ROC analysis was 2.0. Kaplan-Meier analysis demonstrated a significantly higher incidence of mortality in the KRS ≥2 group than in the KRS 0-1 group (log-rank: P < 0.01).ConclusionsThe KRS was useful in Japanese patients with cancer and might be a potentially useful marker for the prediction of mortality. Establishing optimal scores for Japanese subjects is mandatory because of its low diagnostic ability. (KUMAMON Cancer registry; UMIN000047554).
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