Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Stroke severity, early recovery and outcome are each related with clinical classification of stroke: Data from the 'Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Introduction: Baseline severity and clinical stroke syndrome (Oxford Community Stroke Project, OCSP) classification are predictors of outcome in stroke. We used data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’ (TAIST) to assess the relationship between stroke severity, early recovery, outcome and OCSP syndrome. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1,484 patients with acute ischaemic stroke. Severity was measured as the Scandinavian Neurological Stroke Scale (SNSS) at baseline and days 4, 7 and 10, and baseline OCSP clinical classification recorded: total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) and posterior circulation infarction (POCI). Recovery was calculated as change in SNSS from baseline at day 4 and 10. The relationship between stroke syndrome and SNSS at days 4 and 10, and outcome (modified Rankin scale at 90 days) were assessed. Results: Stroke severity was significantly different between TACI (most severe) and LACI (mildest) at all four time points (p<0.001), with no difference between PACI and POCI. The largest change in SNSS score occurred between baseline and day 4; improvement was least in TACI (median 2 units), compared to other groups (median 3 units) (p<0.001). If SNSS did not improve by day 4, then early recovery and late functional outcome tended to be limited irrespective of clinical syndrome (SNSS, baseline: 31, day 10: 32; mRS, day 90: 4); patients who recovered early tended to continue to improve and had better functional outcome irrespective of syndrome (SNSS, baseline: 35, day 10: 50; mRS, day 90: 2). Conclusions: Although functional outcome is related to baseline clinical syndrome (best with LACI, worst with TACI), patients who improve early have a more favourable functional outcome, irrespective of their OCSP syndrome. Hence, patients with a TACI syndrome may still achieve a reasonable outcome if early recovery occurs

Maintenance tyrosine kinase inhibitors following allo-HCT for chronic myeloid leukemia: A CIBMTR Study.

It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myeloid leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML transplanted from 2007-2014 who received maintenance TKI following HCT (n=89) as compared to no TKI maintenance (n=301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy prior to HCT. The majority of patients had disease beyond CP1 at HCT (n=240, 62%). The study was conducted as a landmark analysis, excluding patients that died, relapsed, had chronic graft-versus-host disease or were censored prior to Day 100 following HCT. Of the 89 patients receiving TKI maintenance, 77 (87%) received a single TKI while 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n=50), imatinib (n=27) and nilotinib (n=27). As measured from Day 100, the adjusted estimates for 5-year relapse (maintenance, 35% vs. no maintenance, 26%; p=0.11), leukemia-free survival (LFS, maintenance, 42% vs. no maintenance, 44%; p=0.65) or overall survival (OS, maintenance, 61% vs. no maintenance, 57%; p=0.61) did not significantly differ between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by the status of disease prior to transplant. In conclusion, our data did not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes in a Day 100 landmark analysis. The optimal approach to TKI administration in the post-transplant setting in CML remains undetermined