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

Khorana, Alok A.; Kuderer, Nicole M.; McCrae, Keith R.; Milentijevic, Dejan; Germain, Guillaume; Laliberté, François; MacKnight, Sean D.; Lefèbvre, Patrick; Lyman, Gary H.; Streiff, Michael B.

doi:10.1002/cam4.3437

Cited by 29 publications

(29 citation statements)

References 47 publications

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“… 8 , 9 While many risk factors have been identified for VTE in patients with cancer, advanced disease as well as certain cancer types such as neoplasms of the pancreas, esophagus, and stomach carry the highest risk. 10 , 11 Moreover, patients with cancer have a higher incidence of VTE compared to acutely ill medical patients without cancer. 12 , 13 Despite being a well‐known phenotype for thrombosis, cancer diagnosis and anti‐cancer therapy have not yet been identified as a strong risk factor for COVID‐19–associated thrombosis and the exact thrombotic risk in hospitalized patients with both cancer and COVID‐19 remains unknown.…”

Section: Introductionmentioning

confidence: 99%

The CoVID‐TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID‐19

Kuderer

Hsu

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Hospitalized patients with COVID‐19 have increased risks of venous (VTE) and arterial thromboembolism (ATE). Active cancer diagnosis and treatment are well‐known risk factors; however, a risk assessment model (RAM) for VTE in patients with both cancer and COVID‐19 is lacking. Objectives To assess the incidence of and risk factors for thrombosis in hospitalized patients with cancer and COVID‐19. Methods Among patients with cancer in the COVID‐19 and Cancer Consortium registry (CCC19) cohort study, we assessed the incidence of VTE and ATE within 90 days of COVID‐19–associated hospitalization. A multivariable logistic regression model specifically for VTE was built using a priori determined clinical risk factors. A simplified RAM was derived and internally validated using bootstrap. Results From March 17, 2020 to November 30, 2020, 2804 hospitalized patients were analyzed. The incidence of VTE and ATE was 7.6% and 3.9%, respectively. The incidence of VTE, but not ATE, was higher in patients receiving recent anti‐cancer therapy. A simplified RAM for VTE was derived and named CoVID‐TE ( C ancer subtype high to very‐high risk by o riginal Khorana score +1, V TE history +2, I CU admission +2, D ‐dimer elevation +1, recent systemic anti‐cancer T herapy +1, and non‐Hispanic E thnicity +1). The RAM stratified patients into two cohorts (low‐risk, 0–2 points, n = 1423 vs. high‐risk, 3+ points, n = 1034) where VTE occurred in 4.1% low‐risk and 11.3% high‐risk patients (c statistic 0.67, 95% confidence interval 0.63–0.71). The RAM performed similarly well in subgroups of patients not on anticoagulant prior to admission and moderately ill patients not requiring direct ICU admission. Conclusions Hospitalized patients with cancer and COVID‐19 have elevated thrombotic risks. The CoVID‐TE RAM for VTE prediction may help real‐time data‐driven decisions in this vulnerable population.

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Section: Introductionmentioning

confidence: 99%

The CoVID‐TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID‐19

Kuderer

Hsu

et al. 2021

Journal of Thrombosis and Haemostasis

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“…17,45 Of note, the meta-analysis did not report how the cumulative incidences were calculated, including whether competing risk models were used. Several studies have depicted or reported cumulative incidence by Khorana levels using the Kaplan-Meier function, including the pivotal randomized trials, 9,10,[18][19][20] but failing to account for competing risk of death may overestimate incidence. 46 In the present study, we demonstrated that inappropriate use of the Kaplan-Meier method overestimated risk estimates up to 23% among those with the highest competing mortality risk.…”

Section: Discussionmentioning

confidence: 99%

“…17 Also, some previous studies have ignored competing risk of death, which may lead to an overestimation of venous thromboembolism risk and subsequently overoptimistic claims about the possible absolute risk reduction in a real-world setting. 9,10,[18][19][20] We aimed to assess the clinical potential of using the Khorana score to stratify an unselected sample of Danish ambulatory cancer patients initiating chemotherapy according to risk of incident venous thromboembolism, both overall and by cancer subtypes. We also aimed to quantify the impact of ignoring competing risk of death when estimating absolute risk.…”

Section: Introductionmentioning

confidence: 99%

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

et al. 2022

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The Khorana score is recommended for guiding primary venous thromboembolism prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored competing risk of death, hereby potentially overestimating venous thromboembolism risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated six-month cumulative incidence of venous thromboembolism stratified by Khorana levels. Analyses were conducted with and without considering death as competing risk using the Kaplan-Meier method versus the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40,218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1-2) and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding six-month risks of venous thromboembolism were 1.5% (95% CI 1.3-1-7), 2.8% (95% CI 2.6-3.1), and 4.1% (95% CI 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), six-month risk was 3.6% (95% CI 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to risk of venous thromboembolism, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

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“…Whether a relationship exists between TE and worse cancer outcomes has been controversial, especially in children. Decreased OS following cancer-associated TE has been described in adults with mixed types of cancer [29][30][31] and ALL. 32,33 In children, a recent study by Forbrigger et al found an adverse impact of cancer-associated TE on survival, but the participants with and without TEs had important differences in baseline characteristics, including age and underlying cancer diagnosis, that may at least partly explain differences in cancer outcome.…”

Section: Discussionmentioning

confidence: 99%

Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP‐C

et al. 2021

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There are conflicting data about whether the development of cancer‐associated thrombo‐embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment was associated with overall survival (OS) and event‐free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population‐based retrospective cohort study using the Cancer in Young People‐Canada registry. Children <15 years of age were diagnosed with de novo ALL (2000–2016). The primary exposure variable was radiologically‐confirmed thrombo‐embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo‐embolism on survival, where TE was time‐dependent. We included 2006 children (median age: 4 years, 88.5% precursor B‐cell ALL). Thrombo‐embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range: 35–184 days) after ALL diagnosis. Among standard/low‐risk patients, 41/1165 (3.5%) developed TE while among high/very high‐risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR [aHR] of death: 2.61, 95% CI: 1.62–4.22, p < 0.001) and EFS (aHR of an event [death, relapse, second malignancy]: 2.03, 95% CI: 1.35–3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high‐risk ALL (aHR of death: 2.90, 95% CI: 1.79–4.72, p < 0.001; aHR of an event: 2.02, 95% CI: 1.30–3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high‐risk leukemia.

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

Cited by 29 publications

References 47 publications

The CoVID‐TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID‐19

The CoVID‐TE risk assessment model for venous thromboembolism in hospitalized patients with cancer and COVID‐19

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: A report from CYP‐C

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