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

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

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain.

OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients.

METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials.

RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1).

CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

Khorana score, cancer, heparin, individual participant data meta-analysis, thromboprophylaxis, venous thromboembolism
1538-7933
1940-1951
van Es, Nick
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Ventresca, Matthew
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Di Nisio, Marcello
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Zhou, Qi
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Noble, Simon
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Crowther, Mark
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Briel, Matthias
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Garcia, David
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Lyman, Gary H.
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Macbeth, Fergus
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Griffiths, Gareth
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Iorio, Alfonso
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Mbuagbaw, Lawrence
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Neumann, Ignacio
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Brozek, Jan
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Guyatt, Gordon
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Streiff, Michael B.
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Baldeh, Tejan
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Florez, Ivan D.
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Gurunlu Alma, Ozlem
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Agnelli, Giancarlo
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Ageno, Walter
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Marcucci, Maura
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Bozas, George
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Zulian, Gilbert
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Maraveyas, Anthony
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Lebeau, Bernard
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Lecumberri, Ramon
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Sideras, Kostandinos
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Loprinzi, Charles
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McBane, Robert
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Pelzer, Uwe
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Riess, Hanno
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Solh, Ziad
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Perry, James
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Kahale, Lara A.
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Bossuyt, Patrick M
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Klerk, Clara
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Büller, Harry R.
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Akl, Elie A.
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Schünemann, Holger J.
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IPDMA heparin use in cancer patients research group
van Es, Nick
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Ventresca, Matthew
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Di Nisio, Marcello
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Zhou, Qi
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Noble, Simon
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Crowther, Mark
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Briel, Matthias
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Garcia, David
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Lyman, Gary H.
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Macbeth, Fergus
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Griffiths, Gareth
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Iorio, Alfonso
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Mbuagbaw, Lawrence
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Neumann, Ignacio
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Brozek, Jan
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Guyatt, Gordon
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Baldeh, Tejan
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Florez, Ivan D.
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Gurunlu Alma, Ozlem
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Agnelli, Giancarlo
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Ageno, Walter
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Marcucci, Maura
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Bozas, George
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Zulian, Gilbert
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Maraveyas, Anthony
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Lebeau, Bernard
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Lecumberri, Ramon
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Sideras, Kostandinos
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Loprinzi, Charles
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McBane, Robert
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Pelzer, Uwe
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Riess, Hanno
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Solh, Ziad
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Perry, James
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Kahale, Lara A.
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Bossuyt, Patrick M
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Klerk, Clara
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Büller, Harry R.
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Akl, Elie A.
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Schünemann, Holger J.
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van Es, Nick, Ventresca, Matthew, Di Nisio, Marcello, Zhou, Qi, Noble, Simon, Crowther, Mark, Briel, Matthias, Garcia, David, Lyman, Gary H., Macbeth, Fergus, Griffiths, Gareth, Iorio, Alfonso, Mbuagbaw, Lawrence, Neumann, Ignacio, Brozek, Jan, Guyatt, Gordon, Streiff, Michael B., Baldeh, Tejan, Florez, Ivan D., Gurunlu Alma, Ozlem, Agnelli, Giancarlo, Ageno, Walter, Marcucci, Maura, Bozas, George, Zulian, Gilbert, Maraveyas, Anthony, Lebeau, Bernard, Lecumberri, Ramon, Sideras, Kostandinos, Loprinzi, Charles, McBane, Robert, Pelzer, Uwe, Riess, Hanno, Solh, Ziad, Perry, James, Kahale, Lara A., Bossuyt, Patrick M, Klerk, Clara, Büller, Harry R., Akl, Elie A. and Schünemann, Holger J. , IPDMA heparin use in cancer patients research group (2020) The Khorana score for prediction of venous thromboembolism in cancer patients: an individual patient data meta-analysis. Journal of Thrombosis and Haemostasis, 18 (8), 1940-1951. (doi:10.1111/jth.14824).

Record type: Article

Abstract

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain.

OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients.

METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials.

RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1).

CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

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Manuscript IPDMA Khorana score - Accepted Manuscript
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Accepted/In Press date: 30 March 2020
e-pub ahead of print date: 26 April 2020
Published date: 1 August 2020
Additional Information: Funding Information: NvE has received advisory board honoraria from Bayer, LEO Pharma, and Daiichi Sankyo. DG has been a consultant or received research funding from Boehringer Ingelheim, Bristol‐Myers Squibb, CSL Behring, Daiichi‐Sankyo, Janssen, Pfizer, and Portola. SN is on the advisory boards for Leo Pharma, Pfizer, Bristol Meyers Squibb, and Bayer; he has received honoraria for Leo Pharma, Pfizer, and Boehringer Ingelheim, and has received grants from Leo Pharma and Pfizer. GG has been a consultant for Pfizer on trial design and has also received free drugs from Pfizer for cancer‐related trials under the UK National Cancer Research Institute. MDN has received consulting fees from Bayer Health Care and Grifols. SM has received consulting fees from Portola. MS has received research funding from Portola and has consulted for Daiichi‐Sankyo, Boehringer, Pfizer, and Janssen Healthcare. AM has received advisory board honoraria from Leo Pharma and Bayer. WA has accepted consulting fees from Bayer, Boehringer Ingelheim, Pfizer, Bristol Meyers Squibb, Daiichi‐Sankyo, and Italfarmaco. WA has also received research support from Bayer. MAC reports receiving fees for participation in Data Safety Monitoring committees from Bayer and Daiichi; fees for advisory boards or educational material preparation/presentation from Shionogi, Portola, Octapharma, Bayer, Pfizer, Alexion, and Boehringer Ingelheim; institutional funding from Bayer and Leo Pharma; and personal stock ownership in Alnylam. None of the other authors report any conflicts of interest. Publisher Copyright: © 2020 International Society on Thrombosis and Haemostasis
Keywords: Khorana score, cancer, heparin, individual participant data meta-analysis, thromboprophylaxis, venous thromboembolism

Identifiers

Local EPrints ID: 442511
URI: http://eprints.soton.ac.uk/id/eprint/442511
DOI: doi:10.1111/jth.14824
ISSN: 1538-7933
PURE UUID: be101ec8-9670-4efd-ad87-b7b99d30eead
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

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Date deposited: 17 Jul 2020 16:30
Last modified: 17 Mar 2024 05:44

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Contributors

Author: Nick van Es
Author: Matthew Ventresca
Author: Marcello Di Nisio
Author: Qi Zhou
Author: Simon Noble
Author: Mark Crowther
Author: Matthias Briel
Author: David Garcia
Author: Gary H. Lyman
Author: Fergus Macbeth
Author: Gareth Griffiths ORCID iD
Author: Alfonso Iorio
Author: Lawrence Mbuagbaw
Author: Ignacio Neumann
Author: Jan Brozek
Author: Gordon Guyatt
Author: Michael B. Streiff
Author: Tejan Baldeh
Author: Ivan D. Florez
Author: Ozlem Gurunlu Alma
Author: Giancarlo Agnelli
Author: Walter Ageno
Author: Maura Marcucci
Author: George Bozas
Author: Gilbert Zulian
Author: Anthony Maraveyas
Author: Bernard Lebeau
Author: Ramon Lecumberri
Author: Kostandinos Sideras
Author: Charles Loprinzi
Author: Robert McBane
Author: Uwe Pelzer
Author: Hanno Riess
Author: Ziad Solh
Author: James Perry
Author: Lara A. Kahale
Author: Patrick M Bossuyt
Author: Clara Klerk
Author: Harry R. Büller
Author: Elie A. Akl
Author: Holger J. Schünemann
Corporate Author: IPDMA heparin use in cancer patients research group

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