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Correspondence |

Preventing VTE in Outpatients With CancerPreventing VTE in Outpatients With Cancer FREE TO VIEW

Alok A. Khorana, MD; Alex C. Spyropoulos, MD, FCCP; Jeffrey Zwicker, MD; Gary H. Lyman, MD, MPH; Charles W. Francis, MD
Author and Funding Information

From the James P. Wilmot Cancer Center and Department of Medicine (Drs Khorana, Spyropoulos, and Francis), University of Rochester; Division of Hemostasis-Thrombosis (Dr Zwicker), Beth Israel Deaconess Medical Center, Harvard Medical School; and Duke University and Duke Cancer Institute (Dr Lyman).

Correspondence to: Alok A. Khorana, MD, 601 Elmwood Ave, Box 704, Rochester, NY 14642; e-mail: alok_khorana@urmc.rochester.edu

Funding/Support: Dr Khorana is supported by grants from the National Cancer Institute [K23 CA120587]; the National Heart, Lung, and Blood Institute [R01 HL095109]; and the V Foundation. Drs Lyman and Francis are supported by the National Heart, Lung, and Blood Institute [R01 HL095109]. Dr Lyman is also supported by the National Cancer Institute [RC2 CA148041].

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Zwicker has received funding support from Sanofi-Aventis US LLC. Dr Lyman is co-chair and Drs Khorana and Francis are members of the American Society of Clinical Oncology VTE Guidelines Panel. Dr Francis is a member of a steering committee for a study sponsored by Eisai Co, Ltd, and participates in a registry sponsored by Eisai Co, Ltd. Dr Spyropoulos has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.


Funding/Support: Dr Khorana is supported by grants from the National Cancer Institute [K23 CA120587]; the National Heart, Lung, and Blood Institute [R01 HL095109]; and the V Foundation. Drs Lyman and Francis are supported by the National Heart, Lung, and Blood Institute [R01 HL095109]. Dr Lyman is also supported by the National Cancer Institute [RC2 CA148041].

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Zwicker has received funding support from Sanofi-Aventis US LLC. Dr Lyman is co-chair and Drs Khorana and Francis are members of the American Society of Clinical Oncology VTE Guidelines Panel. Dr Francis is a member of a steering committee for a study sponsored by Eisai Co, Ltd, and participates in a registry sponsored by Eisai Co, Ltd. Dr Spyropoulos has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(1):265-266. doi:10.1378/chest.12-0423
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We applaud the innovations pioneered by the American College of Chest Physicians evidence-based clinical practice guidelines on antithrombotic therapy and prevention of thrombosis (February 2012). However, we are concerned about the resulting recommendations regarding cancer-associated thrombosis, a significant contributor to the public health burden of VTE and an area of particular interest to us.

Regarding prevention of VTE in nonsurgical patients,1 the panel suggested that outpatients with solid tumors with additional risk factors for VTE should receive prophylactic-dose low-molecular-weight heparin or low-dose unfractionated heparin (recommendation 4.2.2). Additional risk factors cited by the panel include hormonal therapy and angiogenesis inhibitors. In our opinion, this recommendation (even as a grade 2B) does not reflect an appropriate interpretation of the results of recent studies on cancer thromboprophylaxis and risk assessment. If these recommendations were to be followed, tens of thousands of women with breast cancer or men with prostate cancer on hormonal therapy for extended periods would receive low-molecular-weight heparin or low-dose unfractionated heparin. The rate of VTE in these patients, however, is much lower than other cancer subgroups, and there are no studies showing a benefit of thromboprophylaxis.2 Similarly, the linkage between antiangiogenic agents, such as bevacizumab, and VTE has not been consistently demonstrated in pooled analyses.3 (Although thalidomide- and lenalidomide-based regimens are associated with VTE, these are used primarily in myeloma and not solid tumors.) Recommendation 4.2.2 further fails to cite important risk factors, such as site of cancer, and a risk assessment model for chemotherapy-associated VTE that has been externally validated in multiple studies; both are the basis for recent and ongoing prophylaxis studies.4

The Institute of Medicine’s 2011 report, Clinical Practice Guidelines We Can Trust, emphasized guideline development group composition and external review.5 Inclusion of oncology content experts on the panel or as external reviewers could have provided a different interpretation of the data and more clinically sound recommendations. We urge the panel to consider such multidisciplinary input for the next iteration of the guidelines. Even weak recommendations formulated without scientific evidence can have a negative impact on patient care and future study design. It is quite possible that institutional review boards may identify these suggestions as the standard of care, affecting future study feasibility. As physicians and researchers involved in this field, we disagree with recommendation 4.2.2 and suggest that clinicians consider recommendations from cancer-focused guidelines, such as those of the American Society of Clinical Oncology and the National Comprehensive Cancer Network.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(suppl):e195S-e226S. [PubMed] [CrossRef]
 
Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299-1309.
 
Hurwitz HI, Saltz LB, Van Cutsem E, et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol. 2011;29(13):1757-1764.
 
Khorana AA. Risk assessment and prophylaxis for VTE in cancer patients. J Natl Compr Canc Netw. 2011;9(7):789-797.
 
Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E., eds; Committee on Standards for Developing Trustworthy Clinical Practice Guidelines Committee on Standards for Developing Trustworthy Clinical Practice Guidelines; Board on Health Care Services Board on Health Care Services; Institute of Medicine of the National Academies Institute of Medicine of the National Academies. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011.
 

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References

Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(suppl):e195S-e226S. [PubMed] [CrossRef]
 
Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299-1309.
 
Hurwitz HI, Saltz LB, Van Cutsem E, et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol. 2011;29(13):1757-1764.
 
Khorana AA. Risk assessment and prophylaxis for VTE in cancer patients. J Natl Compr Canc Netw. 2011;9(7):789-797.
 
Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E., eds; Committee on Standards for Developing Trustworthy Clinical Practice Guidelines Committee on Standards for Developing Trustworthy Clinical Practice Guidelines; Board on Health Care Services Board on Health Care Services; Institute of Medicine of the National Academies Institute of Medicine of the National Academies. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011.
 
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