Genomic Profiles of De Novo High- and Low-Volume Metastatic Prostate Cancer: Results From a 2-Stage Feasibility and Prevalence Study in the STAMPEDE Trial.

PURPOSE: The STAMPEDE trial recruits men with newly diagnosed, high-risk, hormone-sensitive prostate cancer. To ascertain the feasibility of targeted next-generation sequencing (tNGS) and the prevalence of baseline genomic aberrations, we sequenced tumor and germline DNA from patients with metastatic prostate cancer (mPCa) starting long-term androgen-deprivation therapy (ADT). METHODS: In a 2-stage approach, archival, formalin-fixed, paraffin-embedded (FFPE) prostate tumor core biopsy samples were retrospectively subjected to 2 tNGS assays. Prospective enrollment enabled validation using tNGS in tumor and germline DNA. RESULTS: In stage 1, tNGS data were obtained from 185 tumors from 287 patients (65%); 98% had de novo mPCa. We observed PI3K pathway aberrations in 43%, due to PTEN copy-number loss (34%) and/or activating mutations in PIK3 genes or AKT (18%) and TP53 mutation or loss in 33%. No androgen receptor (AR) aberrations were detected; RB1 loss was observed in < 1%. In stage 2, 93 (92%) of 101 FFPE tumors (biopsy obtained within 8 months) were successfully sequenced prospectively. The prevalence of DNA damage repair (DDR) deficiency was 14% (somatic) and 5% (germline). BRCA2 mutations and mismatch repair gene mutations were exclusive to high-volume disease. Aberrant DDR (22% v 15%), Wnt pathway (16% v 4%), and chromatin remodeling (16% v 8%) were all more common in high-volume compared with low-volume disease, but the small numbers limited statistical comparisons. CONCLUSION: Prospective genomic characterization is feasible using residual diagnostic tumor samples and reveals that the genomic landscapes of de novo high-volume mPCa and advanced metastatic prostate cancer have notable similarities (PI3K pathway, DDR, Wnt, chromatin remodeling) and differences (AR, RB1). These results will inform the design and conduct of biomarker-directed trials in men with metastatic hormone-sensitive prostate cancer.

Crisis Management for Biobanks.

All organizations are subject to risk and uncertainty. Adverse events may disrupt normal organizational activity and may even cause complete failure of business operations. Biorepositories are also at risk and there have been instances where multiple samples or entire collections have been destroyed. Biobank guidelines accordingly recommend the establishment of contingency plans to reduce risk to an acceptable level. In this review article, we will use general theory on risk management and illustrate how such principles can be used to establish a practical crisis management plan for any biobank organization.

Biobanking from the patient perspective.

PLAIN ENGLISH SUMMARY: Biobanks are collections of donations of biological material (DNA, cells, tissue etc.) and related data which are very valuable for research into human diseases. A variety of biobanks exist for example within hospitals, research institutes, pharmaceutical companies and patient organisations. The role of patients in biobanking is changing from being seen simply as donors, to actual collaborators in the design, development and the running of biobanks. In this article, we provide a number of examples of patients acting as partners at the heart of biobanking, where their voice and perspective is being seen and used as a valuable resource for the biobank. Our aim is that these examples can be used by those who work with patients in biobank-based research, to design future strategies for patient and public involvement in all biobanks. ABSTRACT: Biobanks and biobanking research plays an increasingly important role in healthcare research and delivery as health systems become more patient-centred and medicine becomes more personalised. There is also growing acceptance and appreciation of the value that patients, patient advocacy organisations and the public can bring as stakeholders in biobanking and more generally in research. Therefore, the importance of active, early and sustained engagement and involvement of patient and public representatives in biobanks will become increasingly relevant. Organising and facilitating patient and public involvement in biobanking takes considerable time and effort for all stakeholders involved. Therefore, for any biobank operator considering involving patients and the public in their biobanking activities, consideration of best practices, current guidance, ethical issues and evaluation of involvement will be important. In this article, we demonstrate that patients are much more than donors to biobanks-they are collaborators at the heart of biobanking with an important voice to identify perspective, which can be an extremely valuable resource for all biobanks to utilise. The case studies herein provide examples of good practice of patient involvement in biobanking as well as outcomes from these practices, and lessons learned. Our aim is to provide useful insights from these efforts and potential future strategies for the multiple stakeholders that work with patients and the public involved in biobank-based research.

Assessing the financial, operational, and social sustainability of a biobank: the Wales Cancer Bank case study.

Biobank sustainability is a multi-faceted concept that many biobanks are wrestling with to justify their continued existence. After 10 years of operation, the Wales Cancer Bank is faced with a potential reduction in grant funding that will result in the need for a restructured approach to patient consenting, sample collection, and sample issue. A review is currently in progress, using evidence from the last 12 months, to inform the decisions that will be taken at the end of 2014 regarding the biobank's future. The information presented details the areas under consideration for revision with the perceived costs and benefits associated with the amendment. Not all outcomes are currently known, and some decisions will be made once the level of future funding is confirmed. The process of assessment has proved to be a valuable exercise and has highlighted the need for biobanks to regularly evaluate strategic principles and operating procedures using sustainability as a denominator.