Management of Cancer-Associated Venous Thrombosis:A Nationwide Survey among Danish Oncologists

Background  Treatment patterns for cancer-associated venous thrombosis (CAT) has been shown to be nonconsistent with contemporary guideline recommendations, resulting in poor patient outcomes. Objectives  The study aimed to describe contemporary CAT management in Danish oncology departments and identify knowledge gaps and inconsistencies between guidelines and clinical practice. Patients and Methods  A survey questionnaire in Danish was developed based on contemporary national guidelines. Using an open recruitment strategy, invitations to participate in the electronic survey were sent to physicians employed at oncology departments in Denmark in winter of 2018/2019. The questionnaire was based on current national guidelines and included 10 items with multiple choices and a free-text option to specify or comment. The questionnaire was pilot-tested by a junior and senior oncologist. Results  A total of 142 physicians completed the survey, representing all Danish geographical regions and various seniority. The majority reported that CAT was treated and followed up in oncology departments. However, 36.6% of the physicians were unaware of the existence of designated cancer thrombosis guidelines. Risk of venous thrombosis was generally assessed without diagnostic scores. Almost all (98.6%) reported low-molecular-weight heparin to be first-line treatment for CAT. Treatment duration seemed wrongly influenced by subtype of venous thrombosis, and 44.5% responded that thromboprophylaxis among hospitalized patients was substantially underused. Conclusion  The variability in the daily clinical management of CAT demonstrated through this survey indicates a potential to increase awareness of available guidelines, standardized use of inpatient thromboprophylaxis, and organized treatment and follow-up in a multidisciplinary setting, which would potentially improve management of CAT in Denmark

Long-Term Management of Pulmonary Embolism:A Review of Consequences, Treatment, and Rehabilitation

The concept of pulmonary embolism is evolving. Recent and emerging evidence on the treatment of specific patient populations, its secondary prevention, long-term complications, and the unmet need for rehabilitation has the potential to change clinical practice for the benefit of the patients. This review discusses the recent evidence from clinical trials, observational studies, and guidelines focusing on anticoagulation treatment, rehabilitation, emotional stress, quality of life, and the associated outcomes for patients with pulmonary embolism. Guidelines suggest that the type and duration of treatment with anticoagulation should be based on prevalent risk factors. Recent studies demonstrate that an anticoagulant treatment that is longer than two years may be effective and safe for some patients. The evidence for extended treatment in cancer patients is limited. Careful consideration is particularly necessary for pulmonary embolisms in pregnancy, cancer, and at the end of life. The rehabilitation and prevention of unnecessary deconditioning, emotional distress, and a reduced quality of life is an important, but currently they are unmet priorities for many patients with a pulmonary embolism. Future research could demonstrate optimal anticoagulant therapy durations, follow-ups, and rehabilitation, and effective patient-centered decision making at the end of life. A patient preferences and shared decision making should be incorporated in their routine care when weighing the benefits and risks with primary treatment and secondary prevention

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

The Khorana score is recommended for guiding primary venous thromboembolism (VTE) prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored the competing risk of death, hereby potentially overestimating VTE risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated 6-month cumulative incidence of VTE stratified by Khorana levels. Analyses were conducted with and without considering death as a competing risk using the Kaplan-Meier method vs the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40 218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1 to 2), and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding 6-month risks of VTE were 1.5% (95% confidence interval [CI], 1.3-1.7), 2.8% (95% CI, 2.6-3.1), and 4.1% (95% CI, 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), the 6-month risk was 3.6% (95% CI, 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk-stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to the risk of VTE, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials

Risk of recurrent cancer-associated venous thromboembolism: A Danish nationwide cohort study

Background Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. Methods Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003–2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. Results The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). Conclusions Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

INTRODUCTION: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS: Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS: For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS: An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors