The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies.

BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

Whole brain radiotherapy improves survival outcomes in primary CNS lymphoma patients ineligible for systemic therapy.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a very rare type of malignancy with a poor prognosis. The role of whole brain radiotherapy (WBRT) in PCNSL has been questioned due to the significant neurotoxicity and lack of convincing data for survival benefit. Even its role in a palliative setting remains to be clearly elucidated. Our study aims to investigate the benefit of WBRT in patients who are ineligible for systemic therapy. METHODS: A single-institution retrospective study was conducted on patients diagnosed with PCNSL between 2002 and 2017. Patients were excluded if they received systemic therapy or focal radiation only. Data on patient demographics and WBRT were collected and correlated with clinical outcomes. RESULTS: A total of 48 patients were selected for analysis, among which 31 (64.6%) patients received WBRT and 17 (35.4%) patients received supportive care only. Patient baseline characteristics were similar between the two groups. Median overall survival (OS) was 4.3 months among the entire cohort. WBRT was associated with improved median OS (8.0 months, range 1.4-62.3 months) compared with supportive care only (3.3 months, range 0.7-18.3 months) (HR 0.39, 95% CI 0.20-0.75, p = 0.005). Among patients who received WBRT, higher radiation dose to the whole brain was not associated with survival (p = 0.10), but higher radiation dose to the gross tumor was associated with improved survival (p = 0.007). CONCLUSION: Patients with PCNSL who are ineligible for systemic therapy may still benefit from WBRT with improvement in survival, compared with the best supportive care. Dose escalation through the addition of a gross tumor boost in these patients was associated with improved overall survival. Further studies in the prospective setting are necessary to confirm the findings from the study.

The Yield of Computed Tomography of the Head Among Patients Presenting With Syncope: A Systematic Review.

BACKGROUND: Overuse of head computed tomography (CT) for syncope has been reported. However, there is no literature synthesis on this overuse. We undertook a systematic review to determine the use and yield of head CT and risk factors for serious intracranial conditions among syncope patients. METHODS: We searched Embase, Medline, and Cochrane databases from inception until June 2017. Studies including adult syncope patients with part or all of patients undergoing CT head were included. We excluded case reports, reviews, letters, and pediatric studies. Two independent reviewers screened the articles and collected data on CT head use, diagnostic yield (proportion with acute hemorrhage, tumors or infarct), and risk of bias. We report pooled percentages, I2 , and Cochran's Q-test. RESULTS: Seventeen articles with 3,361 syncope patients were included. In eight ED studies (n = 1,669), 54.4% (95% confidence interval [CI] = 34.9%-73.2%) received head CT with a 3.8% (95% CI = 2.6%-5.1%) diagnostic yield and considerable heterogeneity. In six in-hospital studies (n = 1,289), 44.8% (95% CI = 26.4%-64.1%) received head CT with a 1.2% (95% CI = 0.5%-2.2%) yield and no heterogeneity. In two articles, all patients had CT (yield 2.3%) and the third enrolled patients ≥ 65 years old (yield 7.7%). Abnormal neurologic findings, age ≥ 65 years, trauma, warfarin use, and seizure/stroke history were identified as risk factors. The quality of all articles referenced was strong. CONCLUSION: More than half of patients with syncope underwent CT head with a diagnostic yield of 1.1% to 3.8%. A future large prospective study is needed to develop a robust risk tool.