Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

Predictors of employment status and stability in Bipolar Disorder: Findings from an 8-year longitudinal study.

INTRODUCTION: Understanding how Bipolar Disorder (BD) affects employment is limited by cross-sectional or short-term longitudinal designs. The aims for this study are to examine condition-related and other clinical predictors of longitudinal employment status and stability in those with BD compared to healthy controls (HC). METHODS: Participants were 358 individuals with BD and HC who were enrolled in the Heinz C. Prechter Longitudinal Study of BD. Participants completed self-report measurements of employment, symptoms, health, personality, life events, and neuropsychological tests at study enrollment, yearly and/or every two months. Repeated measures logistic regression was used to predict employment status and stability. RESULTS: Those with BD were less likely to be employed than HC. Significant predictors of unemployment in BD include having BD type I, younger age, less years with BD, higher depression, worse processing speed, and worse mental and physical health. Of those with BD, 64 % demonstrated greater employment instability compared to 37 % of HC. History of psychosis, worse memory, physical health, and greater disruption of negative life events significantly predicted employment instability. LIMITATIONS: The limitations of this study include the generalizability of this sample, a large reliance of self-report measures, and a lack of employment-related factors such as job-type, functioning, performance, and satisfaction. Lastly, the effects of medication, treatment adherence, and treatment optimization were not assessed in this study. CONCLUSIONS: These findings highlight that different aspects of BD are important for being employed versus maintaining stable employment. These findings indicate the need for more effective treatment strategies beyond symptom management.