Background The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT‐D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. Objectives To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months. Patients/Methods In SELECT‐D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited. Results Ninety‐two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06‐1.58). The major and clinically relevant non‐major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1‐18) and 4% (95% CI, 1‐17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT‐negative cohort (P = .03). Conclusion The SELECT‐D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

Background: Optimal risk stratification of unsuspected pulmonary embolism (UPE) in ambulatory cancer patients (ACPs) remains unclear. Existing clinical predictive rules (CPRs) are derived from retrospective databases and have limitations. The UPE

Background Despite the frequency of venous thromboembolism (VTE) in pancreatic cancer, it is inconsistently reported as an adverse event in clinical trials. We hypothesized that reported rates of VTE in pancreatic cancer clinical trials are influenced by the objectives of the trial, with higher rates reported in thromboprophylaxis compared with chemotherapeutic trials. We performed a systematic review and meta‐analysis of randomized, controlled trials (RCT) in pancreatic cancer to quantify differences in reported rates of VTE in thromboprophylaxis and chemotherapeutic trials. Methods We systematically searched MEDLINE, EMBASE, and Clinicaltrials.gov. Eligible thromboprophylaxis RCTs were required to report rates of thrombosis in non‐anticoagulant pancreatic cancer cohorts. Eligible chemotherapy studies were RCTs evaluating chemotherapy regimens in advanced pancreatic cancer and reported thrombosis as adverse events. Pooled event rates of VTE and arterial thrombosis were calculated using a random‐effects model. Results The pooled VTE rate in 13 chemotherapy studies (5694 patients) was 5.9% (95% confidence interval [CI], 3.9‐9.0%) compared with 16.5% (95% CI, 11.7%‐23.3%; P < .001) in 9 thromboprophylaxis studies (631 patients). The pooled symptomatic VTE rate from chemotherapy studies was 5.4% (95% CI, 3.5%‐8.3%), which was significantly lower than the pooled rate from thromboprophylaxis studies of 10.5% (95% CI, 7.3%‐14.9%; P = .02). Conclusion The VTE incidence reported in chemotherapy RCTs in pancreatic cancer is significantly lower than reported in thromboprophylaxis studies. This finding highlights the underrecognition of VTE in chemotherapeutic trials and emphasizes the need to standardize approaches towards monitoring and reporting of VTE in clinical trials.

Since the development of the Khorana score to predict risk of cancer‐associated venous thromboembolism (VTE), many modified and de novo risk prediction models (RPMs) have been proposed. Comparison of the prognostic performance across models requires comprehensive reporting and standardized methods for model development, validation and evaluation. To improve the standardization of RPM reporting, the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) tool was published in 2015. To better understand the quality of reporting and development of RPMs for cancer‐associated VTE, we performed a literature search of published RPMs and assessed each model using the TRIPOD checklist. Our results yielded 29 RPMs for which 30 items were evaluated. There was a non‐significant (p = 0.15) improvement in reporting of the 30 items in the post‐TRIPOD era (81%) versus the pre‐TRIPOD era (75%). Of seven items (title, sample size, missing data handling, baseline demographics, methods and results for model performance, and supplemental resources) with the lowest reporting in the pre‐TRIPOD era (<70%), there was an average improvement of 22% in the post‐TRIPOD era. Only two of the 22 studies published in the post‐TRIPOD era acknowledged compliance with TRIPOD. Informed by the results of this assessment, the Scientific and Standardization Committee (SSC) Subcommittee on Hemostasis & Malignancy of the International Society on Thrombosis and Hemostasis (ISTH) advocates for standardization of four key elements of RPMs for cancer‐associated VTE: (1) inclusion of the TRIPOD checklist, (2) clear definition of the derivation population, with justification of sample size, (3) clear definition of predictors, and (4) external validation prior to implementation.

Background Patients with cancer‐associated thrombosis (CAT) have a high risk of recurrent venous thromboembolic events, which contribute to significant morbidity and mortality. Direct oral anticoagulants may provide a convenient treatment option for these patients. Objectives To assess clinical characteristics and outcomes of patients with active cancer changing to rivaroxaban after ≥4 weeks of standard therapy for the treatment of venous thromboembolism (VTE) in clinical practice. This analysis focused on secondary outcomes of Cancer‐associated thrOmboSIs – Patient‐reported outcoMes with rivarOxaban (COSIMO). Patients COSIMO was a multinational, prospective, noninterventional, single‐arm cohort study. Overall, 505 patients received at least one dose of rivaroxaban; 96.6% changing from low‐molecular‐weight heparin, 1.6% from a vitamin K antagonist, and 1.8% from fondaparinux. Results Most patients had solid tumors (n = 449; 88.9%) and approximately half of these patients had metastases. The qualifying venous thromboembolic event was deep vein thrombosis (DVT) in 45.3% of patients, pulmonary embolism (PE) in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter‐associated DVT in 7.5% of patients. Approximately 75.1% of patients received rivaroxaban for at least 3 months; 150 (29.7%) patients received concomitant chemotherapy during the study. VTE recurrence, major bleeding, nonmajor bleeding, and major adverse cardiovascular events occurred in 18 (3.6%), 18 (3.6%), 81 (16.0%), and 12 (2.4%) patients, respectively. Conclusions In patients with CAT who changed to rivaroxaban treatment after ≥4 weeks of standard therapy, the observed incidence proportions of recurrent VTE and bleeding events were in keeping with the recognized effectiveness and safety profile of rivaroxaban for the treatment of CAT.

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Background: Advanced pancreatic ductal adenocarcinoma (aPDAC) patients have a lifetime all type thromboembolic event (ATTE) rate of 25-35%. Efficacy and safety of increased dose primary thromboprophylaxis (IDPTP) with low molecular heparin (LMWH) given for 3 months has been shown in two prospective randomized trials. Objectives: To report on efficacy-reduction of all type thromboembolic events (ATTE)-, safety-incidence of Major Bleeding (MB)-and compliance in a single-centre cohort of aPDAC patients receiving first line chemotherapy and LMWH-IDPTP.

BackgroundAdvanced pancreatic ductal adenocarcinoma (aPDAC) patients have a lifetime all type thromboembolic event (ATTE) rate of 25- 35%. Efficacy and safety of increased dose primary thromboprophylaxis (IDPTP) with low molecular heparin (LMWH) given for 3 months has been shown in two prospective randomized trials.ObjectivesTo report on efficacy -reduction of all type thromboembolic events (ATTE)-, safety -incidence of Major Bleeding (MB)- and compliance in a single-centre cohort of receiving first line chemotherapy and LMWH-IDPTP.MethodsFrom May 2009 to October 2016, eighty two patients received IDPTP –LMWH with dalteparin. Schedule: 55kg and below: 7500 IU, between 55 and 80kg: 10,000 IU, above 80kg: 12,500 IU. MB is reported using the International Society of Thrombosis and Haemostasis (ISTH) criteria. ATTE was defined as any arterial or venous event, incidental or clinically symptomatic, including visceral VTE.ResultsMean and median time on dalteparin was 10.2 (95%CI 8.1, 12.4) and 8.0 (95%CI 6.2, 9.7) months respectively. ATTE was observed in 7 (8.5%) of patients, with a mean time on IDPTP of 6.8 months (95% CI 3.5-10.2). MB was seen in 10 (12.2%) patients with a mean time on IDPTP of 7.4 months (95% CI 3.9-10.9). Six major bleeds (60%) were the direct or indirect result of aPDAC. Eighty-one patients had died at the time of data collection with a median overall survival time of 8.7 months (95%CI 6.4, 11.0). Thromboembolism and bleeding were late events. No impact of thromboembolism or bleeding on overall survival was observed. ConclusionsIDPTP-dalteparin was associated with lower ATTE occurrence rates than expected and comparable major bleeding rates. ATTE and MB were late events, the majority of MB was from direct or indirect result of locally progressing aPDAC. Since these conditions can frequently arise in aPDAC, IDPTP should be regularly reviewed beyond 3 months.