To investigate sexual health in breast cancer survivors and their partners, focusing on sexual satisfaction, changes in satisfaction with partner sexuality before vs. after the diagnosis, and unmet informational needs on sexual health in the context of breast cancer. Breast cancer patients and their partners were surveyed at a single time point 1–5 years after having completed primary therapy for breast cancer as part of a cross-sectional study. Study participants completed self-report-questionnaires covering personal characteristics, a question on satisfaction with partner sexuality before (retrospective assessment) versus after the diagnosis (based on the Sexual Medicine Questionnaire for Chronic Diseases (SFCE)), the EORTC (European Organisation for Research and Treatment of Cancer) Sexual Health Questionnaire (EORTC QLQ-SH22) together with the EORTC Quality of Life Core Questionnaire (EORTC QLQ-C30), and a questionnaire assessing sexual health care. Descriptive statistics were used to summarize demographic and clinical data. For group comparisons, dyadic dependencies were accounted for, applying paired t tests when normality (Shapiro–Wilk test) was met and Wilcoxon signed-rank test otherwise. A total of 128 participants (64 patients, 64 partners) were enrolled. Sexual satisfaction did not differ between patients (M = 55, SD = 20.9) and partners (M = 56.7, SD = 20) (t test, p = 0.46). A positive correlation was found between patients’ and partners’ sexual satisfaction (r = 0.62, p < 0.0001). Satisfaction with partner sexuality was lower after diagnosis (p < 0.001, r = 0.54)—with both patients and partners being less satisfied after the diagnosis (M = 2.58, SD = 0.95) than before (M = 3.14, SD = 0.74). Overall, 75
ABSTRACT:Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT. We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multikinase inhibitor dasatinib in adult patients with CBF-AML. Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg daily on days 8 to 21 in induction, and on days 6 to 28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg daily. Primary end point was event-free survival (EFS). Secondary end points included overall survival, relapse-free survival, and cumulative incidence of relapse. A total of 202 patients were randomly assigned to the standard arm (n = 102) and to the dasatinib arm (n = 100). Median age was 49 years (range, 18-77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); and 58 (28.7%) patients had a KIT comutation. There was no statistically significant difference in EFS (hazard ratio, 0.92; 95% confidence interval, 0.63-1.33; P = .66) or secondary end points between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%). In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.ClinicalTrials.gov as NCT02013648.
ABSTRACT:BackgroundCurrent treatment strategies for pediatric intracranial ependymoma do not consider molecular heterogeneity. Here, we evaluated molecular group-specific determinants of outcome and developed an improved risk stratification model. METHODS:Patients aged 0-21 years with localized intracranial ependymoma were enrolled into the prospective clinical trial E-HIT2000. Treatment included maximum safe surgery, local radiotherapy, and chemotherapy, stratified according to age, histology and, following a major amendment, residual tumor. Clinical data were analyzed in a pooled molecularly annotated cohort with data from patients treated analogously within subsequent registries. RESULTS:For 291 trial patients, the 5-year progression-free survival (PFS) and overall survival (OS) were 62 ± 3% and 81 ± 2%, respectively. For the molecularly annotated pooled cohort (n = 228), 5-year PFS/OS were: posterior-fossa group A ependymoma (EPN-PFA) (n = 146): 45 ± 4%/77 ± 4%; posterior-fossa group B ependymoma (EPN-PFB) (n = 19): 90 ± 7%/100%; supratentorial ependymoma, ZFTA fusion-positive (EPN-ZFTA) (n = 59): 64 ± 7%/86 ± 5%; supratentorial ependymoma, YAP1 fusion-positive (EPN-YAP1) (n = 4): 50 ± 25%/100%. Patients with EPN-PFA without molecular risk factors (1q gain, and/or subtype EPN-PFA1c/d/e, 2a), with complete resection, and postoperative radiotherapy showed favorable outcomes (5-year PFS/OS 75 ± 10%/92 ± 7%). For patients with EPN-PFA with molecular risk factors, prognosis was poor irrespective of residual tumor status (5-year PFS/OS: 33 ± 6%/64 ± 6%). Among EPN-ZFTA, 11/59 tumors were classified as EPN-ZFTA with alternative fusions, associated with inferior PFS (5-year PFS/OS: 36 ± 15%/91 ± 9%). For EPN-ZFTA-RELA, homozygous deletions of CDKN2A were associated with unfavorable outcomes (4-year PFS/OS: 19 ± 16%/57 ± 18% vs. 79 ± 7%/97 ± 3%, P = .0001). Finally, we developed a novel stratification model that discriminates standard and intermediate risk patients from those at high risk (P < .0001 for PFS and OS). CONCLUSIONS:These results strongly suggest the inclusion of molecular parameters into stratification and the use of distinct treatment strategies within future ependymoma trials.
The real-time quaking-induced conversion (RT-QuIC) assay has revolutionized prion disease diagnosis by detecting amyloidogenic PrP conformers in different tissue types and body fluids. Recently, we achieved a breakthrough by detecting amyloidogenic PrP conformers in tear fluid (TF), a non-invasive biofluid, warranting further evaluation. We refined our RT-QuIC protocol to assess seeding conversion efficiency using various recombinant substrates, including full-length human (FL Hu), and mutant versions linked to genetic prion diseases, such as E200K and D178N, in both CSF and TF samples. Our study included patients with sporadic and familial prion diseases. FL Hu E200K showed the highest seeding efficiency in cerebrospinal fluid (CSF), with sensitivity increasing from 78 to 93
