Jonathan Wills

Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Enoxaparin dose reduction for thrombocytopenia in patients with cancer: a quality assessment study

The development of thrombocytopenia in the setting of therapeutic anticoagulation for venous thromboembolic disease (VTE) is common in cancer patients, but guidelines for management are based on limited past data and have not been validated. In 2011, Memorial Sloan Kettering Cancer Center (MSKCC) implemented the following guidelines in this setting: administer full dose enoxaparin for a platelet count > 50,000/mcL, half-dose enoxaparin for a platelet count of 25,000–50,000/mcL, and hold anticoagulation for a platelet count < 25,000/mcL. We now report validation of safety and efficacy of these guidelines. As a Quality Assessment Initiative, we evaluated our guidelines for adult cancer patients at MSKCC who were on therapeutic-dose enoxaparin for VTE during the years 2011 through 2013 and experienced at least one 7-day period of thrombocytopenia (platelet count ≤ 50,000/mcL). We assessed adherence to the enoxaparin dose modification guidelines, major bleeding, clinically relevant non-major bleeding, recurrent VTE, and mortality during the thrombocytopenic episodes. We identified 99 patients with 140 episodes of thrombocytopenia of 7 or more days. The median duration of these thrombocytopenic episodes was 12 days. The enoxaparin dose was modified in 133 of the 140 episodes (95%), reflecting satisfactory adherence to our institutional guidelines. There were no recurrent VTE events or major bleeding episodes when the anticoagulant dose was reduced or held. In this cohort, there was only one major bleeding episode, a trauma-associated retroperitoneal hemorrhage that occurred on the third day of a thrombocytopenic episode, prior to enoxaparin dose modification. There were 13 clinically relevant non-major bleeding episodes. Lastly, 10 patients died of cancer-related causes during an episode of thrombocytopenia. This Quality Assessment Initiative supports the safety and efficacy of our guidelines for therapeutic enoxaparin dose modification.

High rate of thiamine deficiency among inpatients with cancer referred for psychiatric consultation: results of a single site prevalence study

Thiamine deficiency (TD) is increasingly recognized in medically ill patients. The prevalence of TD among cancer patients is unknown. This study aims to characterize the prevalence of TD among inpatients with cancer.

Treatment of Central Venous Catheter‐Associated Deep Venous Thrombosis in Cancer Patients with Rivaroxaban

patients treated with conventional ABO identical, leukoreduced, irradiated transfusions. Long-term mortality in recipients of washed transfusions (20–40%) was half to two-thirds of that in the comparable historical comparison group and the current literature (60%) (Supporting Information Table 5). A limitation of these data, in addition to the lack of randomization, is that we did not collect detailed information on treatment regimens (e.g., choice and dose of anthracycline in AML). The striking differences we observed in long-term survival are unlikely solely due to progress in treatment regimens or supportive care. Identical differences were observed when we restricted the comparison to the years 2003–2005 and 2006–2008. For lower risk patients (favorable or intermediate cytogenetics; <46 years of age or younger) in New York State treated between 2006 and 2011 long-term mortality rate was 2.5-fold higher (50% versus 20%) in conventionally treated patients compared with recipients of washed transfusions. This approach has the potential to substantially improve outcomes for many patients with AML. This may be limited, at present, to younger patients with favorable or intermediate cytogenetics. Larger randomized trials will be required to determine whether our promising results are generalizable and reproducible, and whether they might be applicable to older patients (who often receive less intensive therapy), and to patients with other hematologic malignancies or solid tumors.

Automated eligibility screening and monitoring for genotype-driven precision oncology trials

The Information Systems Department at Memorial Sloan Kettering Cancer Center developed the DARWIN Cohort Management System (DCMS). The DCMS identifies and tracks cohorts of patients based on genotypic and clinical data. It assists researchers and treating physicians in enrolling patients to genotype-matched IRB-approved clinical trials. The DCMS sends automated, actionable, and secure email notifications to users with information about eligible or enrolled patients before their upcoming appointments. The system also captures investigators input via annotations on patient eligibility and preferences on future status updates. As of August 2015, the DCMS is tracking 159,893 patients on both clinical operations and research cohorts. 134 research cohorts have been established and track 64,473 patients. 51,192 of these have had one or more genomic tests including MSK-IMPACT, comprising the pool eligible for genotype-matched studies. This paper describes the design and evolution of this Informatics solution.