Anna Falanga

American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer

PURPOSE To develop guideline recommendations for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS A comprehensive systematic review of the medical literature on the prevention and treatment of VTE in cancer patients was conducted and reviewed by a panel of content and methodology experts. Following discussion of the results, the panel drafted recommendations for the use of anticoagulation in patients with malignant disease. RESULTS The results of randomized controlled trials of primary and secondary VTE medical prophylaxis, surgical prophylaxis, VTE treatment, and the impact of anticoagulation on survival of patients with cancer were reviewed. Recommendations were developed on the prevention of VTE in hospitalized, ambulatory, and surgical cancer patients as well as patients with established VTE, and for use of anticoagulants in cancer patients without VTE to improve survival. CONCLUSION Recommendations of the American Society of Clinical Oncology VTE Guideline Panel include (1) all hospitalized cancer patients should be considered for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications; (2) routine prophylaxis of ambulatory cancer patients with anticoagulation is not recommended, with the exception of patients receiving thalidomide or lenalidomide; (3) patients undergoing major surgery for malignant disease should be considered for pharmacologic thromboprophylaxis; (4) low molecular weight heparin represents the preferred agent for both the initial and continuing treatment of cancer patients with established VTE; and (5) the impact of anticoagulants on cancer patient survival requires additional study and cannot be recommended at present.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014

PURPOSE To provide current recommendations about the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials, systematic reviews, meta-analyses, and clinical practice guidelines from November 2012 through July 2014. An update committee reviewed the identified abstracts. RESULTS Of the 53 publications identified and reviewed, none prompted a change in the 2013 recommendations. RECOMMENDATIONS Most hospitalized patients with active cancer require thromboprophylaxis throughout hospitalization. Routine thromboprophylaxis is not recommended for patients with cancer in the outpatient setting. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low-molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those undergoing major abdominal or pelvic surgery with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term secondary prophylaxis (at least 6 months). Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE because of limited data in patients with cancer. Anticoagulation should not be used to extend survival of patients with cancer in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should educate patients about the signs and symptoms of VTE.

Cancer and venous thromboembolism

Neoplastic cells can activate the clotting system directly, thereby generating thrombin, or indirectly, by stimulating mononuclear cells to synthesize and express various procoagulants. Clinical manifestations of increased thrombin generation may be accentuated by down-regulation of endothelial cell counterregulatory mechanisms, such as decreased hepatic synthesis of antithrombin III and protein C. Cancer cells and chemotherapeutic agents can injure endothelial cells, thereby intensifying hypercoagulability. In addition, normal endothelial cell function. may be disrupted by various defects in platelet function. Currently, primary prevention of venous thrombosis should be considered for cancer patients (1) during and immediately after chemotherapy, (2) when long-term indwelling central venous catheters are placed; or (3) when hospitalization for cancer is characterized by prolonged immobilization, trauma, or surgery. Secondary prevention of recurrent venous thrombosis usually necessitates anticoagulation. In some patients with cancer, the condition is resistant to warfarin, and long-term adjusted high-dose heparin is required. For patients unable to tolerate heparin or warfarin because of major bleeding problems, placement of an inferior vena caval filter should be considered. The diagnosis of venous thrombosis may help to uncover previously occult carcinoma by prompting a complete physical examination, chest roentgenography, and mammography. However, extensive cancer screening with total-body computed tomography or magnetic resonance imaging has not been shown to be cost effective for patients with venous thrombosis.

Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial

Summary.  Patients with symptomatic idiopathic venous thromboembolism and apparently cancer‐free have an approximate 10% incidence of subsequent cancer. Apparently cancer‐free patients with acute idiopathic venous thromboembolism were randomized to either the strategy of extensive screening for occult cancer or to no further testing. Patients had a 2‐year follow‐up period. Of the 201 patients, 99 were allocated to the extensive screening group and 102 to the control group. In 13 (13.1%) patients, the extensive screening identified occult cancer. In the extensive screening group, a single (1.0%) malignancy became apparent during follow‐up, whereas in the control group a total of 10 (9.8%) malignancies became symptomatic [relative risk, 9.7 (95% CI, 1.3–36.8; P < 0.01]. Overall, malignancies identified in the extensive screening group were at an earlier stage and the mean delay to diagnosis was reduced from 11.6 to 1.0 months (P < 0.001). Cancer‐related mortality during the 2 years follow‐up period occurred in two (2.0%) of the 99 patients of the extensive screening group vs. four (3.9%) of the 102 control patients [absolute difference, 1.9% (95% CI, −5.5–10.9)]. Although early detection of occult cancers may be associated with improved treatment possibilities, it is uncertain whether this improves the prognosis.

Venous Thromboembolism Prophylaxis and Treatment in Cancer: A Consensus Statement of Major Guidelines Panels and Call to Action

PURPOSE Venous thromboembolism (VTE) is an increasingly frequent complication of cancer and its treatments, and is associated with worsened mortality and morbidity in patients with cancer. DESIGN The Italian Association of Medical Oncology, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the French National Federation of the League of Centers Against Cancer, and the European Society of Medical Oncology have recently published guidelines regarding VTE in patients with cancer. This review, authored by a working group of members from these panels, focuses on the methodology and areas of consensus and disagreement in the various clinical guidelines as well as directions for future research. RESULTS There is broad consensus regarding the importance of thromboprophylaxis in hospitalized patients with cancer, including prolonged prophylaxis in high-risk surgical patients. Prophylaxis is not currently recommended for ambulatory patients with cancer (with exceptions) or for central venous catheters. All of the panels agree that low molecular weight heparins are preferred for the long-term treatment of VTE in cancer. Areas that warrant further research include the benefit of prophylaxis in the ambulatory setting, the risk/benefit ratio of prophylaxis for hospitalized patients with cancer, an understanding of incidental VTE, and the impact of anticoagulation on survival. CONCLUSION We call for a sustained research effort to investigate the clinical issues identified here to reduce the burden of VTE and its consequences in patients with cancer.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Purpose To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. Prophylaxis in the outpatient, inpatient, and perioperative settings was considered, as were treatment and use of anticoagulation as a cancer-directed therapy. Methods A systematic review of the literature published from December 2007 to December 2012 was completed in MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed evidence to determine which recommendations required revision. Results Forty-two publications met eligibility criteria, including 16 systematic reviews and 24 randomized controlled trials. Recommendations Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for outpatients with cancer. It may be considered for selected high-risk patients. Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low–molecular weight heparin (LMWH) or low-dose aspirin. Patients undergoing major cancer surgery should receive prophylaxis, starting before surgery and continuing for at least 7 to 10 days. Extending prophylaxis up to 4 weeks should be considered in those with high-risk features. LMWH is recommended for the initial 5 to 10 days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term (6 months) secondary prophylaxis. Use of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE. Anticoagulation should not be used for cancer treatment in the absence of other indications. Patients with cancer should be periodically assessed for VTE risk. Oncology professionals should provide patient education about the signs and symptoms of VTE. J Clin Oncol 31:2189-2204.

A Validated Risk Score for Venous Thromboembolism Is Predictive of Cancer Progression and Mortality

BACKGROUND Retrospective studies have suggested an association between cancer-associated venous thromboembolism (VTE) and patient survival. We evaluated a previously validated VTE Clinical Risk Score in also predicting early mortality and cancer progression. METHODS A large, nationwide, prospective cohort study of adults with solid tumors or lymphoma initiating chemotherapy was conducted from 2002 to 2006 at 115 U.S. practice sites. Survival and cancer progression were estimated by the method of Kaplan and Meier. Multivariate analysis was based on Cox regression analysis adjusted for major prognostic factors including VTE itself. RESULTS Of 4,405 patients, 134 (3.0%) died and 330 (7.5%) experienced disease progression during the first 4 months of therapy (median follow-up 75 days). Patients deemed high risk (n = 540, 12.3%) by the Clinical Risk Score had a 120-day mortality rate of 12.7% (adjusted hazard ratio [aHR] 3.00, 95% confidence interval [CI] 1.4-6.3), and intermediate-risk patients (n = 2,665, 60.5%) had a mortality rate of 5.9% (aHR 2.3, 95% CI 1.2-4.4) compared with only 1.4% for low-risk patients (n = 1,200, 27.2%). At 120 days of follow-up, cancer progression occurred in 27.2% of high-risk patients (aHR 2.2, 95% CI 1.4-3.5) and 16.4% of intermediate-risk patients (aHR 1.9, 95% CI 1.3-2.7) compared with only 8.5% of low-risk patients (p < .0001). CONCLUSION The Clinical Risk Score, originally developed to predict the occurrence of VTE, is also predictive of early mortality and cancer progression during the first four cycles of outpatient chemotherapy, independent from other major prognostic factors including VTE itself. Ongoing and future studies will help determine the impact of VTE prophylaxis on survival. IMPLICATIONS FOR PRACTICE The risk of venous thromboembolism (VTE) is increased in patients receiving cancer chemotherapy. In this article, the authors demonstrate that a popular risk score for VTE in patients with cancer is also associated with the risk of early mortality in this setting. It is important that clinicians evaluate the risk of VTE in patients receiving cancer treatment and discuss the risk and associated symptoms of VTE with patients. Individuals at increased risk should be advised that VTE is a medical emergency and should be urgently diagnosed and appropriately treated to reduce the risk of serious and life-threatening complications.

Thrombosis and cancer: emerging data for the practicing oncologist.

The American Society of Clinical Oncology (ASCO) recently updated clinical practice guidelines on the treatment and prevention of venous thromboembolism (VTE) in patients with cancer. Although several new studies have been reported, many questions remain about the close relationship between VTE and malignant disease. The risk of VTE among patients with cancer continues to increase and is clearly linked to patient-, disease- and treatment-specific factors. In general, VTE among patients with cancer is treated in a similar fashion to that in other patient populations. However, the greater risk of VTE in patients with cancer, the multitude of risk factors, and the greater risk of VTE recurrence and mortality among patients with cancer pose important challenges for surgeons, oncologists, and other providers.

American Society of Clinical Oncology 2007 clinical practice guideline recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer

Purpose To d e v e lop guid e lin e re co m m e ndations for th e us e of anticoagulation in th e pre v e ntion and tre at m e nt of v e nous thro m bo e m bolis m (VT E) in patie nts w ith canc er. Methods A co m pre h e nsiv e syst e m atic re vie w of th e m e dical lit erature on th e pre v e ntion and tre atm e nt of VT E in canc er patie nts w as conduct e d and re vie w e d by a pan e l of cont e nt and m e thodology e xp erts. F ollo w ing discussion of th e re sults, th e pan e l draft e d re co m m e ndations for th e us e of anticoagulation in patie nts w ith m alignant dis e as e . Results Th e re sults of rando m iz e d controlle d trials of prim ary and s e condary VT E m e dical prophylaxis, surgical prophylaxis, VT E tre atm e nt, and th e im pact of anticoagulation on survival of patie nts w ith canc er w ere re vie w e d. R e co m m e ndations w ere d e v e lop e d on th e pre v e ntion of VT E in hospitaliz e d, a m bulatory, and surgical canc er patie nts as w e ll as patie nts w ith e stablish e d VT E , and for us e of anticoagulants in canc er patie nts w ithout VT E to im prov e survival. Conclusion R e co m m e ndations of th e A m erican Socie ty of C linical O ncology VT E G uid e lin e Pan e l includ e (1) all hospitaliz e d canc er patie nts should b e consid ere d for VT E prophylaxis w ith anticoagulants in th e abs e nc e of ble e ding or oth er contraindications; (2) routin e prophylaxis of a m bulatory canc er patie nts w ith anticoagulation is not re co m m e nd e d , w ith th e e xc e pt ion of pat i e nts re c e iv ing tha lido m id e or l e na lido m id e ; (3) pat i e nts und ergo ing m a jor surg ery for m a lignant d is e as e shou ld b e cons id ere d for pharm aco log ic thro m boprophy lax is; (4) lo w m o l e cu lar w e ight h e parin re pre s e nts th e pre f erre d ag e nt for both th e in it ia l and cont inu ing tre at m e nt of canc er pat i e nts w ith e stab lish e d VT E ; and (5) th e i m pact of ant icoagu lants on canc er pat i e nt surv iva l re qu ire s add it iona l study and cannot b e re co m m e nd e d at pre s e nt . J C lin O nco l 25 .

Treatment of Venous Thromboembolism

There have been some important advances in the treatment of venous thromboembolism during the past 18 months. A randomized trial has confirmed earlier observations indicating an adequate initial heparin effect is required to prevent recurrent venous thromboembolism, and it is critical to achieve this effect within the first 24 hours of therapy. The need to use a validated protocol for administering intravenous heparin is now firmly established. The clinician has a choice between two protocols that have been validated by randomized trials and provide both effective and safe heparin therapy. For patients with clinically suspected pulmonary embolism, the clinician now has a practical noninvasive strategy that avoids pulmonary angiography, identifies patients with proximal-vein thrombosis who require treatment, and avoids the need for treatment and further investigation in the majority of patients.