The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta‐analysis

Es, Nick van; Ventresca, Matthew; Nisio, Marcello Di; Zhou, Qi; Noble, Simon; Crowther, Mark; Briel, Matthias; García, David; Lyman, Gary H.; Macbeth, Fergus; Griffiths, Gareth; Iorio, Alfonso; Mbuagbaw, Lawrence; Neumann, Ignacio; Brožek, Jan; Guyatt, Gordon; Streiff, Michael B.; Baldeh, Tejan; Flórez, Iván D.; Alma, Özlem Gürünlü; Agnelli, Giancarlo; Ageno, Walter; Marcucci, Maura; Bozas, George; Zulian, Gilbert; Maraveyas, Anthony; Lebeau, B.; Lecumberri, Ramón; Sideras, Kostandinos; Loprinzi, Charles L.; McBane, Robert D.; Pelzer, Uwe; Riess, Hanno; Solh, Ziad; Perry, James; Kahale, Lara A; Bossuyt, Patrick M.; Klerk, Clara P.W.; Büller, Harry R.; Akl, Elie A.; Schünemann, Holger J.

doi:10.1111/jth.14824

Cited by 69 publications

(45 citation statements)

References 50 publications

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“…In the same line, analyses of patient cohorts focusing on specific cancer sites, such as pancreatic cancer or lung cancer, showed poor performance of the Khorana score [46,47]. A recent meta-analysis revealed that the predictive power of the Khorana score was not homogenous across various types of cancer [48]. The pan-cancer Khorana score does not capture the disease-specific characteristics associated with VTE risk, and clinicians should be cautious when applying the Khorana score as a universal risk assessment tool.…”

Section: Risk Assessment Modelsmentioning

confidence: 99%

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis

Hohaus

Bartolomei

Cuccaro

et al. 2020

Cancers

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Lymphoma is listed among the neoplasias with a high risk of venous thromboembolism (VTE). Risk factors for VTE appear to differ from risk factors in solid tumors. We review the literature of the last 20 years for reports identifying these risk factors in cohorts consisting exclusively of lymphoma patients. We selected 25 publications. The most frequent studies were analyses of retrospective single-center cohorts. We also included two reports of pooled analyses of clinical trials, two meta-analyses, two analyses of patient registries, and three analyses of population-based databases. The VTE risk is the highest upfront during the first two months after lymphoma diagnosis and decreases over time. This upfront risk may be related to tumor burden and the start of chemotherapy as contributing factors. Factors consistently reported as VTE risk factors are aggressive histology, a performance status ECOG ≥ 2 leading to increased immobility, more extensive disease, and localization to particular sites, such as central nervous system (CNS) and mediastinal mass. Association between laboratory values that are part of risk assessment models in solid tumors and VTE risk in lymphomas are very inconsistent. Recently, VTE risk scores for lymphoma were developed that need further validation, before they can be used for risk stratification and primary prophylaxis. Knowledge of VTE risk factors in lymphomas may help in the evaluation of the individual risk-benefit ratio of prophylaxis and help to design prospective studies on primary prophylaxis in lymphoma.

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Section: Risk Assessment Modelsmentioning

confidence: 99%

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis

Hohaus

Bartolomei

Cuccaro

et al. 2020

Cancers

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“…33 Four included studies were identified through 1 individual patient data metaanalysis in which the Khorana score was calculated post hoc for participants in 7 RCTs evaluating thromboprophylaxis. 34 Four of these RCTs fulfilled the eligibility criteria and were included in the analysis. [35][36][37][38] The 6 included RCTs had enrolled a total of 7180 ambulatory cancer patients, of whom 4626 (64%) had an intermediate to high risk of VTE based on a Khorana score of $2 points.…”

Section: Resultsmentioning

confidence: 99%

“…36 In all 4 studies that evaluated LMWH, [35][36][37][38] the Khorana score was calculated post hoc. 34 In 5 studies, chemotherapy was initiated after randomization in all study patients, 14,15,[35][36][37] whereas in 1 study, 83% of patients were treated with chemotherapy after randomization. 38 Maximum follow-up duration varied between studies: 6 months, 14,15 12 months, 35 18 months, 36 or until death.…”

Section: Resultsmentioning

confidence: 99%

“…36,38 In addition, discrimination of the score seems to be poor in specific cancer types (eg, lung cancer), whereas it is much better in others. 2,34,50 Finally, the sensitivity of the Khorana score is modest; 75% of VTE events do not occur in the group at high risk of VTE (Khorana score $3 or higher), and 50% do not occur in the group at intermediate to high risk of VTE (Khorana score $2). Consequently, half of all ambulatory cancer patients who develop VTE will not be identified as potential candidates for thromboprophylaxis with this score.…”

Section: Discussionmentioning

confidence: 96%

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Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

et al. 2020

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Guidelines suggest thromboprophylaxis for ambulatory cancer patients starting chemotherapy with an intermediate to high risk of venous thromboembolism (VTE) according to Khorana score. Data on thromboprophylaxis efficacy in different Khorana score risk groups remain ambiguous. We sought to evaluate thromboprophylaxis in patients with an intermediate- to high-risk (≥2 points) Khorana score and an intermediate-risk score (2 points) or high-risk score (≥3 points) separately. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) comparing thromboprophylaxis with placebo or standard care in ambulatory cancer patients. Outcomes were VTE, major bleeding, and all-cause mortality. Relative risks (RRs) were calculated in a profile-likelihood random-effects model. Six RCTs were identified, involving 4626 cancer patients. Thromboprophylaxis with direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH) significantly reduced VTE risk in intermediate- to high-risk (RR, 0.51; 95% confidence interval [CI], 0.34-0.67), intermediate-risk (RR, 0.58; 95% CI, 0.36-0.83), and high-risk patients (RR, 0.45; 95% CI, 0.28-0.67); the numbers needed to treat (NNTs) were 25 (intermediate to high risk), 34 (intermediate risk), and 17 (high risk), respectively. There was no significant difference in major bleeding (RR, 1.06; 95% CI, 0.69-1.67) or all-cause mortality (RR, 0.90; 95% CI, 0.82-1.01). The numbers needed to harm (NNHs) for major bleeding in intermediate- to high-risk, intermediate-risk, and high-risk patients were 1000, −500, and 334, respectively. The overall NNH was lower in DOAC studies (100) versus LMWH studies (−500). These findings indicate thromboprophylaxis effectively reduces the risk of VTE in patients with an intermediate- to high-risk Khorana score, although the NNT is twice as high for intermediate-risk patients compared with high-risk patients.

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“…The risk of VTE varies widely among cancer patients 8 . The Khorana score (KS) is an externally validated risk prediction clinical algorithm 9‐23 to assess the risk of VTE in patients with cancer. This score uses multiple independent predictors, including the tumor's primary site, pre‐chemotherapy platelet count, hemoglobin levels < 100 g/L or use of red blood cell growth factors, pre‐chemotherapy leucocyte count > 11 x 10 9 /L, and body mass index (BMI) ≥ 35 kg/m 2 24 .…”

Section: Introductionmentioning

confidence: 99%

Cancer associated thrombosis and mortality in patients with cancer stratified by khorana score risk levels

et al. 2020

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Background The Khorana score (KS) clinical algorithm is used to predict VTE risk in cancer patients. The study objective was to evaluate VTE and survival rates among patients newly diagnosed with cancer and stratified by KS in a real‐world population. Methods Data from the Optum® Clinformatics® DataMart database between 01/01/2012–09/30/2017 was used to identify adults with ≥ 1 hospitalization or ≥ 2 outpatient claims with a cancer diagnosis (index date). Only patients who were initiated on chemotherapy or radiation therapy were included. Patients were classified based on KS (KS = 0, 1, 2 or ≥ 3). Time‐to‐first VTE and survival were evaluated from the index date to the earliest among end of data availability or insurance coverage, death, or 12 months post‐index using Kaplan‐Meier (KM) analyses. Results A total of 2,488 (KS = 0); 2,125 (KS = 1), 1,074 (KS = 2), and 507 (KS ≥ 3) cancer patients were included. The 12‐month KM rates of VTE were 3.1%, 5.4%, 7.9%, and 14.9% (associated median time to VTE of 2.7, 3.0, 1.4, and 1.7 months) among KS = 0, 1, 2, and ≥ 3 cohorts, respectively. Corresponding adjusted hazard ratios (95% CIs) relative to the KS = 0 cohort were 1.72 (1.25‐2.38), 2.46 (1.73‐3.50), and 4.99 (3.40‐7.31) for the KS = 1, 2, and ≥ 3 cohorts, respectively (all P < .001). Regardless of KS, patients with VTE had significantly lower survival rates than those without. Conclusions This real‐world claims‐based cohort study of newly diagnosed cancer patients showed significantly higher rates of VTE with increased KS, confirming its predictive ability. Moreover, VTE was associated with lower survival rates within each KS cohort.

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The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta‐analysis

Cited by 69 publications

References 50 publications

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis

Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis

Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis

Cancer associated thrombosis and mortality in patients with cancer stratified by khorana score risk levels

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