Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

BACKGROUND: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. OBJECTIVE: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. DESIGN, SETTING, AND PARTICIPANTS: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). INTERVENTION: Gene expression analysis was used to assign subtypes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. RESULTS AND LIMITATIONS: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. CONCLUSIONS: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. PATIENT SUMMARY: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation.

An International Survey of Brain Banking Operation and Characterization Practices.

Brain banks continue to make a major contribution to the study of neurological and psychiatric disorders. The current complexity and scope of research heighten the need for well-characterized cases and the demand for larger cohorts and necessitate strategies, such as the establishment of bank networks based in regional areas. While individual brain banks have developed protocols that meet researchers' needs within the confines of resources and funding, to further promote collaboration, standardization and scientific validity and understanding of the current protocols of participating banks are required. A survey was sent to brain banks, identified by an Internet search, to investigate operational protocols, case characterization, cohort management, data collection, standardization, and degree of collaboration between banks. The majority of the 24 banks that returned the survey have been established for more than 20 years, and most are affiliated with a regional network. While prospective donor programs were the primary source of donation, the data collected on donors varied. Longitudinal information assists case characterization and enhances the analysis capabilities of research. However, acquiring this information depended on the availability of qualified staff. Respondents indicated a high level of importance for standardization, but only 8 of 24 considered this occurred between banks. Standard diagnostic criteria were not achieved in the classification of controls, and some banks relied on the researcher to indicate the criteria for classification of controls. Although the capacity to collaborate with other banks was indicated by 16 of 24 banks, this occurred infrequently. Engagement of all brain banks to participate toward a consensus of diagnostic tools, especially for controls, will strengthen collaboration.

Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk.

OBJECTIVES: To evaluate the ability of the Decipher genomic classifier in predicting metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens. MATERIALS AND METHODS: Fifty-seven patients with available biopsy specimens were identified from a cohort of 169 men treated with radical prostatectomy in a previously reported Decipher validation study at Cleveland Clinic. A Cox multivariable proportional hazards model and survival C-index were used to evaluate the performance of Decipher. RESULTS: With a median follow up of 8 years, 8 patients metastasized and 3 died of prostate cancer. The Decipher plus National Comprehensive Cancer Network (NCCN) model had an improved C-index of 0.88 (95% confidence interval [CI] 0.77-0.96) compared to NCCN alone (C-index 0.75, 95% CI 0.64-0.87). On multivariable analysis, Decipher was the only significant predictor of metastasis when adjusting for age, preoperative prostate-specific antigen and biopsy Gleason score (Decipher hazard ratio per 10% increase 1.72, 95% CI 1.07-2.81, P = .02). CONCLUSION: Biopsy Decipher predicted the risk of metastasis at 10 years post radical prostatectomy. While further validation is required on larger cohorts, preoperative knowledge of Decipher risk derived from biopsy could indicate the need for multimodality therapy and help set patient expectations of therapeutic burden.