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Predicting cancer-associated venous thromboembolism
quence, the proportion of thromboembolic events that occur in the high-risk group increases from 23% to 55% (Figure 3). It is a matter of debate whether the 9% risk of VTE during the first six months is considered high enough to justify thromboprophylaxis.
The primary aim of risk stratification with the Khorana score is to select cancer patients with a high risk of VTE suitable for long-term thromboprophylaxis. A meta-analy- sis of randomized trials that compared low-molecular- weight heparins in prophylactic doses in cancer patients with placebo showed an absolute risk reduction of approximately 50% during a median follow-up of ten months (RR 0.54; 95%CI: 0.38-0.75), with an increase in major bleeding events (RR 1.44; 95%CI: 0.98-2.11).19 As the estimated 6-month incidence of VTE in cancer patients with a high Khorana score is 11.0%, thromboprophylaxis with low-molecular-weight heparins for cancer patients in this group could result in a number requiring treatment of approximately 19 when extrapolating the relative risk reduction of 0.54. When considering patients with 2 points or more as high-risk, thromboprophylaxis with low-molecular-weight heparins could result in a number requiring treatment of 24. Recent trials showed an accept- able safety profile of therapeutic doses of direct oral anti- coagulants in cancer patients compared to low-molecular- weight heparins.20,21 Since their oral administration makes these drugs more convenient, long-term thromboprophy- laxis would be less burdensome and, therefore, more like- ly to be accepted by clinicians and patients. Whether the safety and efficacy of prophylactic doses of direct oral anticoagulants are comparable to that of low-molecular- weight heparin in cancer patients needs to be established.
The present meta-analysis shows that the Khorana score can select high-risk patients for thromboprophylaxis overall. These findings indicate that the Khorana score may help clinicians in selecting patients at high risk of VTE for thromboprophylaxis, which is in support of the suggestions presented in some guidelines and could accel- erate their implementation in clinical practice. However, several limitations of the Khorana need to be taken into account, including the different in predicted performance across cancer types and the modest proportion of patients with VTE assigned to the high-risk group. Several other VTE prediction tools for cancer patients have been intro- duced, which may have a better performance than the Khorana score;22-24 these scores, however, require prospec- tive validation. Development of risk prediction models for bleeding events in patients with prophylactic anticoagu-
lants could help to carefully weigh the benefit risk trade- off for thromboprophylaxis in cancer patients. In addition, future prediction tools should aim to address the limita- tions of the Khorana score, as outlined by this analysis. Novel biomarkers or genetic information from tumor biopsies could improve prediction of VTE and, therefore, merit investigation.
CAT-prediction collaborators
Abdel-Razeq H, King Hussein Cancer Center, Jordan; Ades S, University of Vermont, Burlington, VT, USA; Ayappan SR, The Ohio State University Comprehensive Cancer Center (OSUCCC-James), Columbus, OH, USA; Borchmann S, University Hospital Cologne, Germany; Cella CA, Federico II University, Naples, Italy; Fankhauser CD, University Hospital Zürich, Switzerland; Ferroni P, San Raffaele Roma Open University, Italy; Fuentes HE, John Stronger Jr. Hospital, Chicago, IL, USA; Kruger S, Ludwig-Maximilians-University of Munich, Germany; Lim SH, Samsung Medical Center, Seoul, Republic of Korea; Lubberts S, University Medical Center Groningen, the Netherlands; Lustig DB, University of Ottawa, ON, Canada; Mansfield AS, Mayo Clinic, Rochester, MN, USA; Munõz Martín AJ, Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Noble S, Cardiff University, UK; Panizo E, University Clinic of Navarra, Pamplona, Spain; Papaxoinis G, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Park K, Pusan National University Yangsan Hospital, Republic of Korea; Patel JN, Levine Cancer Institute, NC, USA; Posch F, Medical University of Vienna, Austria; Ramos JD, University of Washington, Seattle, WA, USA; Roselli M, University of Rome Tor Vergata, USA; Santi R, A.O.SS. Antonio e Biagio e Cesare Arrigo of Alessandria, Italy; Sohal D, Cleveland Clinic, OH, USA; Srikanthan A, Princess Margaret Cancer Centre, University of Toronto, ON, USA; Tafur AJ, University of Oklahoma Health Sciences Center, USA; Terbuch A, Medical University, Graz, Austria; Thomas M, University College London Hospitals NHS Foundation Trust, UK; Vathiotis O, Oncology Unit, Sotiria General Hospital, University of Athens, Greece; Wang R, Graduate School of Tianjin Medical University, PRC; Zahir MN, Aga Khan University Hospital, Pakistan.
Funding
This study was supported by an unrestricted grant from LeoPharma. The sponsor had no influence on study design, data collection, analysis, writing of the manuscript, or in the decision to submit the manuscript for publication.
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