Profiling of Oncology Patients as Part of Clinical Care and Research

PROSPER is a pilot project that will assess the ability to integrate genomic results into patient care and research.

All patients will be consented to be involved. Involvement will be completely voluntary. Patients with gynaecological cancers or patients potentially eligible for a phase I trial who are receiving cancer care under medical oncology at Auckland City Hospital will be approached to consider participation in this study. All patients who are over 18 and potentially eligible for further therapy (standard of care or as part of a clinical trial) will be considered.

Patients who agree to participate in PROSPER will provide archived tumour specimens (primary tumour and/or metastasis; tumour block or 15-20 unstained paraffin-embedded slides [minimum of 15 unstained slides if block not available], plus one H&E stained slide). Molecular profiling will be performed at the University of Auckland taking advantage of local expertise. A hybridisation capture DNA sequencing approach obtaining 500x-1000x coverage of a panel of 578 cancer genes will be used. This approach has recently been used to successfully analyse over 40 paired tumour and normal FFPE tissues by Prof. Cristin Print's University of Auckland laboratory (NimbleGen comprehensive cancer panel). Tumour tissue that remains after molecular profiling will be banked (with patients' consent) and may be subject to additional genomic sequencing analysis (e.g. whole genome sequencing), RNA expression analysis (Affymetrix Primeview), protein expression analysis (e.g. Western blot, IHC), and/or DNA copy number analysis (e.g. array CGH, quantitative PCR, FISH) based on resources available. Only validated results of these analyses will be conveyed to treating physicians and made available in patients' records.

Patients must agree to provide whole blood for biobanking. This will provide a source of normal DNA for differentiation of constitutional versus somatic (tumour) molecular changes. Blood samples will also be used to detect circulating tumour DNA to assess this as an alternative to fresh biopsies.

On documentation of relapse patients will be asked (where feasible) to provide a tumour biopsy and blood sample for further profiling. As biopsies become an increasingly common requirement in clinical trials, willingness of patients, procedural safety and useful tissue acquisition are critical elements of success. In patients with high grade serous ovarian cancer research biopsies have been shown to be safe, and feasible. In this project, investigators will collect ctDNA (circulating tumour DNA) alongside tumour biopsies to allow correlation and validation of the role of ctDNA as a non-invasive alternative to biopsies. Relating baseline expression profiles to treatment outcomes for each patient will help optimise drug therapy by improving patient selection and monitoring. This project will build upon plasma genomic initiatives already underway in breast, colorectal, and neuroendocrine cancers.