Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration‐resistant cancer patients

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.34 ◽

2011 ◽

pp. 191-204

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

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Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Oncology Reviews ◽

10.4081/oncol.2011.191 ◽

2011 ◽

Vol 5 (3) ◽

pp. 191

Author(s):

Alpesh N. Amin ◽

Steven B. Deitelzweig

Keyword(s):

At Risk ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Assessment Model ◽

Major Surgery ◽

Medical Illness ◽

Patients With Cancer ◽

Increased Risk ◽

National Quality ◽

American Society

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

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Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review

Cancers ◽

10.3390/cancers12030612 ◽

2020 ◽

Vol 12 (3) ◽

pp. 612 ◽

Cited By ~ 1

Author(s):

Anne Rossel ◽

Helia Robert-Ebadi ◽

Christophe Marti

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Absolute Risk ◽

Narrative Review ◽

Relative Reduction ◽

Number Needed To Treat ◽

Chemotherapeutic Regimen ◽

Patients With Cancer ◽

Increased Risk ◽

Risk Of Cancer

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk–benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

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YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

Pharmacogenomics ◽

10.2217/pgs-2020-0008 ◽

2020 ◽

Vol 21 (13) ◽

pp. 919-928

Author(s):

Ana Afonso ◽

Jani Silva ◽

Ana Rita Lopes ◽

Sara Coelho ◽

Ana Sofia Patrão ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Patients ◽

Cox Regression ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Allelic Discrimination ◽

Cox Regression Analysis ◽

Castration Resistant ◽

Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

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Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽

10.1182/blood.v112.11.3824.3824 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3824-3824

Author(s):

Cihan Ay ◽

Rainer Vormittag ◽

Daniela Dunkler ◽

Ralph Simanek ◽

Alexandru-Laurentiu Chiriac ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Predictive Value ◽

Significant Risk ◽

Cumulative Probability ◽

Total Study Population ◽

Cox Regression Analysis ◽

Increased Risk ◽

Diagnosis Of Cancer ◽

D Dimer

Abstract Venous thromboembolism (VTE) is a frequent complication of cancer, which represents a major cause of morbidity and mortality in cancer patients. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. D-Dimer is a global indicator of coagulation activation and fibrinolysis and is frequently elevated in cancer patients, even without thrombosis. The measurement of D-dimer levels is a widely applied test in the diagnostic work-up of patients with suspected VTE. Prospective observational studies have shown that D-dimer levels have a predictive value for the risk of recurrence in non-cancer patients after the discontinuation of oral anticoagulant treatment. Whether testing for D-Dimer at diagnosis of cancer would be useful for prediction of cancer-associated thrombosis, is not elucidated because up to now appropriately designed prospective studies have not yet been carried out. Therefore, we have assessed D-Dimer levels in cancer patients as risk predictor for VTE and provide a report from the ongoing prospective observational CATS, which was initiated in October 2003. Patients with newly diagnosed cancer or progression of disease that had neither chemotherapy within the last three months, nor radiotherapy nor surgery within the last two weeks were recruited and followed prospectively. Occurrence of VTE and information on the patients’ anti-cancer-treatment within the follow up period were recorded. Observation ended with occurrence of VTE, death or after 2 years. VTE has always been confirmed by imaging. D-Dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan Meier and Cox regression analysis were applied for statistical calculation. Data on 821 patients with cancer (370 women/451 men, median age [IQR]: 62 [53–68] yrs) were available for analyses. Patients were followed for a median observation time of 454 days. Main tumour entities were malignancies of the breast (n=132), lung (n=119), upper (n=35) and lower gastrointestinal tract (n=106), pancreas (n=46), kidney (n=22) and prostate (n=101). Furthermore, 102 patients had high-grade glioma, 94 lymphomas, 17 multiple myeloma and 47 other tumour types. During the observation period VTE occurred in 62 patients (24 female/38 male, median age [IQR]: 60 [50–66] yrs). Elevated levels of D-Dimer (cut-off level 1.44 μg/ml, representing the 75th percentile of the total study population) [hazard ratio (HR): 2.4, 95% CI 1.4–4.0], surgery [HR: 2.3, 95% CI 1.0–5.3] and radiotherapy [HR: 2.3, 95% CI 1.2–4.4] were statistically significant risk factors for VTE in multivariate analysis including D-Dimer, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of developing VTE after 6 months was 11.2 % in patients with D-Dimer levels above and 4.2 % in those below the 75th percentile (p=0.003). In conclusion, cancer patients with elevated D-Dimer levels have an approximately 3-fold increased risk for future occurrence of VTE. High levels of D-Dimer independently predict VTE in these patients and D-Dimer measurement at diagnosis of cancer would help identify patients at increased risk for VTE.

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Statins and Venous Thromboembolism In Lung Cancer

Blood ◽

10.1182/blood.v116.21.5122.5122 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5122-5122

Author(s):

Moh'd Khushman ◽

Abdel-ghanie Abu-samra ◽

Shatha Farhan ◽

Gordon Jacobsen ◽

Amr Hanbali ◽

...

Keyword(s):

Lung Cancer ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Lipid Lowering ◽

Coagulation Cascade ◽

Controlled Study ◽

Increased Risk ◽

Statin Use

Abstract Abstract 5122 Background: Dyslipidemia plays a major role in the pathophysiology of atherosclerosis which may also contributed to an increased risk of and thromboembolism from the injury of the vascular endothelium and its activation of platelets, thereafter, the coagulation cascade. It has been well-established that the use of statins in patients with dyslipidemia reduces cardiovascular events and mortality, therefore, improves survival. In addition to a cholesterol-lowering effect, statins exhibit antithrombotic and anti-inflammatory properties that may confer a protective benefit to an increased risk of thromboembolism in cancer patients. Several case-controlled studies reported that cancer patients receiving long-term statins, but not other non-statin lipid lowering treatment, had a lower incidence of venous thromboembolism. Methods: To investigate any protective benefit from statin use in lung cancer patients, we have conducted this retrospective, case-controlled study. Total of 1548 patients with lung cancer were included from the tumor registery at Henry Ford Health System, Detroit, Michigan, between January 1999 and December 2004. The data were extracted from available electronic medical records of these patients. Statistical analyses were performed and stratified for statin users versus non statin users. Results: Out of 1,548 patients, 315 patients (average age was 68, range 46–90) were statin users at the time of their lung cancer diagnosis. The remaining 1233 patients (average age was 65.9, range 29–94) were non- statin users. After stratifying for statin use, 25 of the 315 statin users developed DVT/PE (7.9%), while 100 of the 1233 non-statin users developed DVT/PE (8.1%). This potential benefit from statin use can also be better visualized from comparing the development of DVT/PE between the statin and non-statin groups in a Kaplan-Meier curve for the probability of freedom from DVT/PE across time. Though statistical significance was not reached (log-rank p-value = 0.377), a trend towards a slightly decreased incidence of DVT/PE onset in the patients who receiving statin as the lipid-lowering agent has been observed. Conclusion: Based on our preliminary data, statin use in patients with lung cancer has demonstrated a weak but favorable protective effect on the development of a venous thromboembolism. The nature as a retrospective study and not well-balanced two group of patients (e.g., the average age of statin users were 2 years older than the non-statin users) may limit our results from reaching statistical significance. In addition, some of the patients who had no clear documentation of their home medications had also been categorized as non-statin users in our study. The results from our final data analysis will be presented. Disclosures: No relevant conflicts of interest to declare.

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Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment

Current Oncology ◽

10.3747/co.22.2587 ◽

2015 ◽

Vol 22 (2) ◽

pp. 144 ◽

Cited By ~ 33

Author(s):

J.C. Easaw ◽

M.A. Shea-Budgell ◽

C.M.J. Wu ◽

P.M. Czaykowski ◽

J. Kassis ◽

...

Keyword(s):

Venous Thromboembolism ◽

Renal Insufficiency ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Factor Xa ◽

Patients With Cancer ◽

Clinical Scenarios ◽

Increased Risk

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic.PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations.Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti–factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

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Evaluation of Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in the Oncology Population

Blood ◽

10.1182/blood.v128.22.5026.5026 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5026-5026

Author(s):

Jessica Hedvat ◽

Christina Howlett ◽

James K. McCloskey ◽

Ruchi Jain

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Cancer Patients ◽

Bleeding Episode ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Package Insert ◽

Increased Risk ◽

Clinically Significant ◽

Risk For Bleeding

Abstract INTRODUCTION: Anticoagulant management of cancer-associated thrombosis is challenging since this patient population is concurrently at an increased risk for bleeding. The use of direct oral anticoagulants [(DOACs) dabigatran, rivaroxaban, apixaban] is not recommended for the treatment of venous thromboembolism (VTE) in cancer patients since there is limited data in this patient population. Despite limited evidence for use, DOACs are commonly prescribed due to ease of administration and lack of required laboratory monitoring. The objective of this study was to evaluate the practice and safety patterns of the DOACs when used for VTE treatment in the oncology population at Hackensack University Medical Center (HackensackUMC). METHODS: This study was a retrospective chart review of adult cancer patients treated at HackensackUMC who received dabigatran, rivaroxaban, or apixaban for the treatment of VTE. The protocol was reviewed and approved by the Institutional Review Board. Patients were identified through a computer generated report of the DOACs which included patients on all inpatient adult oncology floors at HackensackUMC from January 2013 to October 2015. Patients were included in this study if they were 18 years of age or older, admitted to an oncology floor, receiving a DOAC for VTE treatment for at least 48 hours, and had active cancer. Patients were excluded from this study if they were receiving hemodialysis or receiving a DOAC exclusively for the indication of atrial fibrillation. The primary outcomes of this study included the percentage of patients who were receiving a DOAC dosage consistent with that of the package insert and the percentage of patients who experienced clinically significant bleeding. The secondary outcomes of this study included the percentage of patients who had their DOAC held for thrombocytopenia and high risk procedures. Descriptive statistics were used to analyze study outcomes. RESULTS: Of the 126 patients screened, 39 patients were included. Thirty-five patients were on rivaroxaban and 4 patients were on apixaban (Table 1). Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with that of the package insert. Of these 10 patients identified, the majority were receiving a lower DOAC dose than is recommended in the package insert. Our assumption is that these patients received a lower than recommended dose due to concerns for increased risk of bleeding. No patients experienced clinically significant bleeding. Four of 39 patients (10%) experienced a minor bleeding episode, all of which were gastrointestinal and/or genitourinary bleeds (Table 2). Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia (none of which experienced a bleeding episode). All patients had their DOACs appropriately held for all procedures. CONCLUSION: Increased education and awareness on manufacturer recommended dosing of DOACs is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. To our knowledge, this is the first study to evaluate the use of DOACs for VTE treatment in patients with cancer at a high risk for bleeding. This data suggests that the use of DOACs may be safe to use for VTE treatment in the oncology population. This study may provide foundation for larger, randomized, controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients. Disclosures Howlett: Eisai: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Sandoz: Honoraria; Teva: Speakers Bureau. McCloskey:Ariad: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau.

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Association of smoking and cancer with the risk of venous thromboembolism: the Scandinavian Thrombosis and Cancer cohort

Scientific Reports ◽

10.1038/s41598-021-98062-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benedikte Paulsen ◽

Olga V. Gran ◽

Marianne T. Severinsen ◽

Jens Hammerstrøm ◽

Søren R. Kristensen ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Smoking Status ◽

Large Population ◽

Population Based ◽

Cancer Site ◽

Established Risk Factor ◽

Increased Risk ◽

Active Cancer

AbstractSmoking is a well-established risk factor for cancer, and cancer patients have a high risk of venous thromboembolism (VTE). Conflicting results have been reported on the association between smoking and risk of VTE, and the effect of smoking on VTE-risk in subjects with cancer is scarcely studied. We aimed to investigate the association between smoking and VTE in subjects with and without cancer in a large population-based cohort. The Scandinavian Thrombosis and Cancer (STAC) cohort included 144,952 participants followed from 1993–1997 to 2008–2012. Information on smoking habits was derived from self-administered questionnaires. Active cancer was defined as the first two years following the date of cancer diagnosis. Former smokers (n = 35,890) and those with missing information on smoking status (n = 3680) at baseline were excluded. During a mean follow up of 11 years, 10,181 participants were diagnosed with cancer, and 1611 developed incident VTE, of which 214 were cancer-related. Smoking was associated with a 50% increased risk of VTE (HR 1.49, 95% CI 1.12–1.98) in cancer patients, whereas no association was found in cancer-free subjects (HR 1.07, 95% CI 0.96–1.20). In cancer patients, the risk of VTE among smokers remained unchanged after adjustment for cancer site and metastasis. Stratified analyses showed that smoking was a risk factor for VTE among those with smoking-related and advanced cancers. In conclusion, smoking was associated with increased VTE risk in subjects with active cancer, but not in those without cancer. Our findings imply a biological interaction between cancer and smoking on the risk of VTE.

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