Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data

Background:

Venous thromboembolism (VTE) is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high-risk periods may provide the opportunity for better targeted intervention.

Methods:

We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprises 10 598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer.

Results:

People with lung cancer had an overall VTE incidence of 39.2 per 1000 person-years (95% confidence interval (CI), 35.4–43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were metastatic disease (hazard ratio (HR)=1.9, CI 1.2–3.0 vs local disease); adenocarcinoma subtype (HR=2.0, CI 1.5–2.7, vs squamous cell; chemotherapy administration (HR=2.1, CI 1.4–3.0 vs outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2–2.3 vs other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE.

Conclusions:

People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma or are undergoing chemotherapy. The presence of VTE is an independent risk factor for death.     

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.     

Frequency, clinical pattern and outcome of thrombosis in cancer patients in Saudi Arabia

Objectives: Thrombotic risk is increased in patients with cancer and there are important implications forthose who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinicalpatterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma)patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographicsand clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patientswith cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidentalfinding on routine workup in 28% . Cancer and VTE were diagnosed at the same time in 38% of patients, and47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE postcancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTEwere present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time ofthrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Mostcommon types of tumors associated with thrombosis were breast cancer, non-Hodgkin’s lymphoma and lungcancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients withsymptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can developin a significant number of patients with cancer, and almost half of the patients have additional risk factors forVTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarterof cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed toaccurately define the extent of this problem and to develop effective prophylactic strategies.     

High incidence of silent venous thromboembolism before treatment in ovarian cancer

Venous thromboembolism (VTE) such as deep-vein thrombosis (DVT) and pulmonary thromboembolism (PTE) often occurs after surgery and rarely occurs even before surgery in patients with ovarian cancer. It is well known that levels of plasma D-dimer (DD) before treatment in most ovarian cancer patients are increased. This study therefore examined whether increased levels of DD are associated with presence of VTE before treatment of ovarian cancer. Between November 2004 and March 2007, DD levels prior to initial treatment were measured in 72 consecutive patients with presumed epithelial ovarian cancer (final diagnosis: epithelial ovarian cancer, n=60; and epithelial ovarian borderline malignancy, n=12). Venous ultrasound imaging (VUI) of the lower extremity was conducted for all patients except for two patients in whom DVT was detected by pelvic computed tomography (CT). When DVT was found, pulmonary scintigraphy was subsequently performed to ascertain presence of PTE. D-dimer levels were above the cut-off value (0.5 microg ml(-1)) in 65 of 72 patients (90.2%). Venous ultrasound imaging or CT revealed DVT in 18 of 72 patients (25.0%) and pulmonary scintigraphy found PTE in 8 patients (11.1%). All patients with VTE were asymptomatic when VTE was found. D-dimer levels were associated with incidence of VTE (0-1.4 microg ml(-1); 0 of 26 (0%), 1.5-7.4 microg ml(-1); 9 of 30 (30%) and > or =7.5 microg ml(-1); 9 of 16 (56.3%), P for trend=0.0003). However, even if 1.5 microg ml(-1) was used as a cut-off value, this had low specificity and positive predictive value (47.2, 38.3%), though it had high sensitivity and negative predictive value (100, 100%). Therefore, ovarian cancer patients with DD level > or =1.5 microg ml(-1) should be examined using VUI to detect silent DVT. Patients with VTE underwent preventive managements including anticoagulant therapy before initial treatment, chemotherapy or surgery, and after surgery. There was no clinical onset of postoperative VTE in all 72 patients. Measurement of DD levels and subsequent ultrasonography revealed that silent or subclinical VTE frequently occurs before surgery in ovarian cancer. The usefulness of preoperative assessment of VTE needs further confirmation in randomised controlled trials.     

意义未明的单克隆免疫球蛋白病血栓栓塞并发症的研究进展

意义未明的单克隆免疫球蛋白病（MGUS）患者静脉血栓栓塞（VTE）的过度危险已有报道。群体研究MGUS 1年-、5年-和10年-静脉血栓形成（VT）的危险性。深静脉血栓形成（DVT）和肺栓塞（PE）危险、动脉血栓形成、冠状动脉和脑血管事件的危险均增加。IgM MGUS患者并无血栓形成增加的危险,而IgG/IgA MGUS患者静脉血栓形成的危险增加4倍。血栓形成的危险不随诊断时M-蛋白浓度（〉10.0g/L或〈10.0g/L）而变动。伴/不伴血栓形成的MGUS患者血栓形成的危险未超过MM或原发性巨球蛋白血症（WM）。伴比不伴血栓形成的MGUS患者其5年和10年生存率差。     

意义未明的单克隆免疫球蛋白病血栓栓塞并发症的研究进展

意义未明的单克隆免疫球蛋白病(MGUS)患者静脉血栓栓塞(VTE)的过度危险已有报道。群体研究MGUS 1年-、5年-和10年-静脉血栓形成(VT)的危险性。深静脉血栓形成(DVT)和肺栓塞(PE)危险、动脉血栓形成、冠状动脉和脑血管事件的危险均增加。IgM MGUS患者并无血栓形成增加的危险,而IgG/IgA MGUS患者静脉血栓形成的危险增加4倍。血栓形成的危险不随诊断时M-蛋白浓度(>10.0g/L或<10.0g/L)而变动。伴/不伴血栓形成的MGUS患者血栓形成的危险未超过MM或原发性巨球蛋白血症(WM)。伴比不伴血栓形成的MGUS患者其5年和10年生存率差。     

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.     

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

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.     

Treatment of thromboembolic complications in patients with brain tumors

Thromboembolic disease is common in patients with malignant brain tumors and represents a major cause of morbidity and mortality in these patients. The presenting signs and symptoms of deep venous thrombosis and pulmonary emboli can be subtle; thus, a high index of suspicion is required to ensure a timely diagnosis. The accuracy of non-invasive studies of the lower extremities and lungs have significant limitations. Venography and pulmonary angiography remain the best diagnostic techniques when difficult decisions arise regarding the need for anticoagulants in these patients.Patients with malignant brain tumors can be safely anticoagulated with heparin and warfarin, if these agents are monitored carefully. Continuous intravenous infusions of heparin are associated with lower risks of bleeding than intermittent boluses. Clinicians may wish to modify the recommended initial bolus dose of heparin in patients without life-threatening thromboembolic disease. Warfarin reduces the incidence of recurrent thromboembolic events. The incidence of warfarin-related bleeding can be lowered without compromising efficacy by maintaining the PT ratio at 1.3. Potential warfarin drug interactions must be considered, aspirin containing medications and NSAIDS should be avoided, and the platelet count should be kept above 50,000 using transfusions if required to prevent potentially life-threatening bleeding in anticoagulated patients. Thrombolytics are contraindicated in this patient population. Vena caval filters and thrombectomy are rarely required. Additional research is needed to determine the best techniques to prevent deep venous thrombosis and pulmonary embolism in patients with brain tumors.     

Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients

BACKGROUND: Venous thromboembolism (VTE) contributes to morbidity and mortality in cancer patients and is a frequent complication of anticancer therapy. In the current study, the frequency, risk factors, and trends associated with VTE were examined among hospitalized cancer patients. METHODS: A retrospective cohort study was conducted using the discharge database of the University HealthSystem Consortium. This included 1,824,316 hospitalizations between 1995 and 2003 at 133 U.S. medical centers. RESULTS: Among 1,015,598 cancer patients, 34,357 (3.4%) were diagnosed with deep venous thrombosis and 11,515 with pulmonary embolism (PE) (1.1%) for an overall VTE rate of 4.1%. Subgroups of cancer patients with the highest rates included black ethnicity (5.1% per hospitalization) and those receiving chemotherapy (4.9%). Sites of cancer with the highest rates of VTE included pancreas (8.1%), kidney (5.6%), ovary (5.6%), lung (5.1%), and stomach (4.9%). Among hematologic malignancies, myeloma (5%), non-Hodgkin lymphoma (4.8%), and Hodgkin disease (4.6%) had the highest rates of VTE. The rate of VTE increased by 28%, secondary to a near-doubling of PE rates from 0.8% to 1.5% (P < .0001). Among patients receiving chemotherapy, the rates of VTE rose from 3.9% to 5.7%, an increase of 47% (P < .0001). In multivariate analysis, risk factors associated with VTE included age >or=65 years, female sex, black ethnicity, use of chemotherapy, primary site of cancer, presence of comorbidities, and year of admission. CONCLUSIONS: VTE, particularly PE, is an increasingly frequent complication of hospitalization in cancer patients. Patients with black ethnicity, specific sites of cancer, or those receiving chemotherapy are disproportionately at risk.     

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of 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 can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.     

Prophylaxis of venous thromboembolism in brain tumor patients

Summary Thromboembolism is a common problem in patients with brain tumors. Within this population are subpopulations of patients at varying but substantial risk for deep vein thrombosis and pulmonary embolism. Prophylactic strategies can be applied to these various risk groups that will dramatically reduce the incidence of thromboembolism, and these should be applied on a routine basis. The standard prophylactic methods for thromboembolic prophylaxis include mechanical devices (e.g., graduated leg stockings; external pneumatic calf compression) and pharmacological agents (e.g., low dose heparin). In addition, a basic knowledge of low molecular weight heparins and heparinoids is essential because these new agents have a potentially promising role in the prophylaxis of neurological disease in certain patients. The principles concerning the prophylaxis of venous thromboembolic disease in patients with brain tumors are addressed in this review.     

Androgen deprivation and thromboembolic events in men with prostate cancer

BACKGROUND:

Androgen deprivation therapy (ADT) improves prostate cancer outcomes in specific clinical settings, but is associated with adverse effects, including cardiac complications and possibly thromboembolic complications. The objective of this study was to estimate the impact of ADT on thromboembolic events (TEs) in a population‐based cohort.

METHODS:

In the linked Surveillance, Epidemiology and End Results–Medicare database, we identified men older than 65 who were diagnosed with nonmetastatic prostate cancer between 1999 and 2005. Medical or surgical ADT was identified by Medicare claims for gonadotropin‐releasing hormone agonists or bilateral orchiectomy at any time following diagnosis. TEs included deep venous thrombosis, pulmonary embolism, and arterial embolism. The impact of ADT on the risk of any TE and on total number of events was estimated, controlling for patient and tumor characteristics.

RESULTS:

Of 154,611 patients with prostate cancer, 58,466 (38%) received ADT. During a median follow‐up of 52 months, 15,950 men had at least 1 TE, including 8829 (55%) who had ADT and 7121 (45%) with no ADT. ADT was associated with increased risk of a TE (adjusted hazard ratio = 1.56; 95% confidence interval, 1.50‐1.61; P < .0001), and duration of ADT was associated with the total number of events (P < .0001).

CONCLUSIONS:

In this population‐based cohort, ADT was associated with increased risk of a TE, and longer durations of ADT were associated with more TEs. Men with intermediate‐ and low‐risk prostate cancer should be assessed for TE risk factors before starting ADT and counseled regarding the risks and benefits of this therapy. Cancer 2011. © 2011 American Cancer Society.     

肺癌静脉血栓栓塞的危险因素及生物标志物的研究进展

癌症是引起静脉血栓栓塞(venous thromboembolism,VTE)的重要危险因素,而VTE是引起肿瘤患者死亡的重要原因。肺癌患者VTE的发生率在不同的研究中结果有所差别,发生率从7%~13%不等,其中还包括大量可疑肺栓塞病例。肺癌患者VTE发生的危险因素可以分为三类:患者自身特征、肿瘤相关因素以及治疗相关的因素。此外,许多生物标志物也被发现可以作为VTE发生的危险因素(例如D-二聚体)。了解肺癌VTE发生的危险因素对于预防血栓并发症的发生、改善肺癌患者的治疗方面具有重要的意义。本文就VTE危险因素及生物标志物进行综述。     

切除修复交叉互补基因1与卵巢癌发病的相关性

目的:探索ERCC1与卵巢癌发病的相关性.方法:收集2013年至2016来我院就诊的卵巢癌患者30例作为病例组,以同一时期来我体检中心常规体检的患者61例作为对照组,进行病例-对照研究.分析研究对象ERCC的单核细胞多态性.结果:ERCC1-8092TT基因型携带者的卵巢癌发生概率高于8092CC基因型,但未见统计学差异.结论:中国北方人群ERCC1基因多态性与卵巢癌发病无相关性.未来需要开展基于人群的大样本随机抽样研究以验证这一结论.