The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity

Fatigue is a common side effect of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients. However, the prevalence of TKI-induced fatigue remains uncertain and little is known about predictors of fatigue and its relationship with physical activity. In this study, 220 CML patients receiving TKI therapy and 110 gender- and age-matched controls completed an online questionnaire to assess fatigue severity and fatigue predictors (Part 1). In addition, physical activity levels were objectively assessed for 7 consecutive days in 138 severely fatigued and non-fatigued CML patients using an activity monitor (Part 2). We demonstrated that the prevalence of severe fatigue was 55.5% in CML patients and 10.9% in controls (P<0.001). We identified five predictors of fatigue in our CML population: age (OR 0.96, 95% CI 0.93-0.99), female gender (OR 1.76, 95% CI 0.92-3.34), Charlson Comorbidity Index (OR 1.91, 95% CI 1.16-3.13), the use of comedication known to cause fatigue (OR 3.43, 95% CI 1.58-7.44), and physical inactivity (OR of moderately active, vigorously active and very vigorously active compared to inactivity 0.43 (95% CI 0.12-1.52), 0.22 (95% CI 0.06-0.74), and 0.08 (95% CI 0.02-0.26), respectively). Objective monitoring of activity patterns confirmed that fatigued CML patients performed less physical activity on both light (P=0.017) and moderate to vigorous intensity (P=0.009). In fact, compared to the non-fatigued patients, fatigued CML patients performed 1 hour less of physical activity per day and took 2000 fewer steps per day. Our findings facilitate the identification of patients at risk of severe fatigue and highlight the importance to set the reduction of fatigue as a treatment goal in CML care. This study was registered at The Netherlands Trial Registry, NTR7308 (Part 1) and NTR7309 (Part 2)

Karyotype - Phenotype Associations in Patients with Turner Syndrome

Variation in karyotype may be associated with the phenotype of patients with Turner syndrome (TS). Our objective was to identify these associations between karyotype and phenotype in TS patients. This study was part of the European multicentre dsd-LIFE study. We evaluated the associations between different karyotypes of TS patients and age at diagnosis, Turner stigmata, cardiac/renal involvement and gonadal function. Information was available for 328 TS patients. Participants had a monosomy 45,X (46%), mosaicism 45,X/46,XX (10%), karyotype with isochromosome (18%), or other karyotype (26%). The clinical signs of TS were the most severe in patients with monosomy 45,X and the least severe in patients with mosaicism 45,X/46,XX. Patients with isochromosome and y-material showed an intermediate phenotype. Despite the more severe features in patients with monosomy 45,X, the median age at diagnosis was only slightly lower compared to patients with other karyotypes, which suggests opportunities for improvement of knowledge and diagnostics

Efficacy of internet-based cognitive behavioral therapy for treatment-induced menopausal symptoms in breast cancer survivors:Results of a randomized controlled trial

PURPOSE We evaluated the effect of Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, on the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms (primary outcomes), sleep quality, HF/NS frequency, sexual functioning, psychological distress, and health-related quality of life in breast cancer survivors with treatment-induced menopausal symptoms. PATIENTS AND METHODS We randomly assigned 254 breast cancer survivors to a therapist-guided or a selfmanaged iCBT group or to a waiting list control group. The 6-week iCBT program included psycho-education, behavior monitoring, and cognitive restructuring. Questionnaires were administered at baseline and at 10 weeks and 24 weeks postrandomization. We used mixed-effects models to compare the intervention groups with the control group over time. Significance was set at P <.01. An effect size (ES) of .20 was considered small, .50 moderate and clinically significant, and .80 large. RESULTS Compared with the control group, the guided and self-managed iCBT groups reported a significant decrease in the perceived impact of HF/NS (ES, .63 and .56, respectively; both P <.001) and improvement in sleep quality (ES, .57 and .41; both P <001). The guided group also reported significant improvement in overall levels of menopausal symptoms (ES, .33; P = .003), and NS frequency (ES, .64; P <001). At longer-term followup (24 weeks), the effects remained significant, with a smaller ES for the guided group on perceived impact of HF/NS and sleep quality and for the self-managed group on overall levels of menopausal symptoms. Additional longer-term effects for both intervention groups were found for hot flush frequency. CONCLUSION iCBT, with or without therapist support, has clinically significant, salutary effects on the perceived impact and frequency of HF/NS, overall levels of menopausal symptoms, and sleep quality