Purpose: To evaluate efficacy and safety of venetoclax þ azacitidine among treatment-na€ ve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax þ azacitidine or placebo þ azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax þ azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax þ azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m 2 ; days 1-7/28-day cycle).Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax þ azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)þCR with incomplete hematologic recovery (CRi)] rates (venetoclax þ azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax þ azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/ 11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax þ azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax þ azacitidine group.Conclusions: Patients with IDH1/2mut who received venetoclax þ azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.

Purpose: To evaluate efficacy and safety of venetoclax+azacitidine among treatment-naïve patients with FLT3 mutant acute myeloid leukemia.Patients and Methods: Data were pooled from patients enrolled in a Phase 3 study (NCT02993523) that compared patients treated with venetoclax+azacitidine or placebo+azacitidine and a prior Phase 1b study (NCT02203773) where patients were treated with venetoclax+azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or co-morbidities. Patients on venetoclax+azacitidine received Ven 400 mg orally (days 1-28) and azacitidine (75 mg/m 2 ; days 1-7/28day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates.Results: In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax+azacitidine and azacitidine groups. Composite complete remission (CRc, complete remission [CR]+CR with incomplete hematologic recovery [CRi]) rates (venetoclax+azacitidine /azacitidine) for FLT3 mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. In patients treated with venetoclax+azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77%, median OS was 9.9 and 19.2 months, and in co-mutated FLT3-ITD+NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax+azacitidine group. Conclusion:When treated with venetoclax+azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax+azacitidine in patients harboring FLT3-ITD.Research.

In a routine clinical setting, the higher the mpMRI PI-RADS, the greater the detection rate of csPCa in biopsy-naïve men. A normal mpMRI does not exclude csPCa; however, mpMRI may have utility in informing shared-decision making on whether to proceed to biopsy and subsequent treatment.

This is the largest, contemporary cohort of ORCs in England, encompassing >80% of all performed operations. We now know the current standard for ORC in England. This provides the basis for individual surgeons and units to compare their outcomes and a standard with which future techniques and modifications can be compared.

OBJECTIVE External ventricular drains (EVDs) have an important role in the management of neurological disease, and their placement is a frequently performed neurosurgical procedure. Hemorrhage is a common complication of EVD placement and occurs more frequently than originally believed. There is also risk of hemorrhage with removal of an EVD, which has not been well described. The authors investigated the risk factors associated with placement and removal of EVDs at their institution. METHODS A database was created including patients who required EVD placement from March 2008 to June 2014 at the University of Minnesota. A retrospective chart review was completed, and data were collected for each patient. All cranial imaging studies during the index hospitalization were reviewed to identify hemorrhages associated with either EVD placement or removal. The study was performed using a research protocol approved by the University of Minnesota's institutional review board. RESULTS Four hundred eighty-two EVDs were placed during the designated time period. Among the cases in which patients underwent imaging after the placement procedure, hemorrhage was found in 94 (21.6%). The hemorrhage volume ranged from 0.003 cm to 45.9 cm (mean [± SD] 1.96 ± 6.48 cm). Two of these hemorrhages resulted in additional interventions: 1 surgical evacuation and 1 contralateral EVD. In 55 (22.5%) of the 244 cases in which imaging was performed after EVD removal, hemorrhage associated with removal was identified. The mean volume of these hemorrhages was 8.25 ± 20.34 cm (range 0.012-82.08 cm). Two EVDs were replaced, and 1 patient died as a result of a large hemorrhage. Large hemorrhages (> 30 cm) occurred in 2 patients on placement (0.46%) and in 5 patients on removal (2.0%). In this series, decreased platelet levels on admission and an increasing number of EVD placement attempts correlated with an increased risk of hemorrhage on placement. Only those with an EVD placed at bedside were more likely to have hemorrhage on EVD removal. CONCLUSIONS Multiple studies have reported varying EVD hemorrhage rates while very few studies have described hemorrhage secondary to EVD removal. This is the first reported analysis of risk factors associated with hemorrhage on EVD removal. Hemorrhages occur relatively frequently following EVD placement and removal, though clinical significance of these events seems to be low.