Gynecological malignancies comprise 19% of new cancer diagnoses and deaths and up to 50% of these are classified as rare cancers (RC). RC are associated with a poor outcome due to delay in diagnosis, misclassification of RC subtypes and lack of evidence-based treatments/access. We designed the WEHI-Stafford Fox Rare Cancer Program with streamlined ethics, governance, consenting processes, including remote consent from home anywhere in Australia, and data collection protocols to allow data and tissue analysis of any RC type. We have clinical and laboratory RC databases with BioGrid Australia, using the online REDCap platform. We process tumour and blood samples to generate PBMCs, DNA, RNA; including for NGS including Whole Genome Sequencing (WGS); patient-derived xenografts (PDX), organoids, cell lines and other derivatives.
We have 329 RC patients accrued, including 269 patients categorized into 15 distinct rare gynaecological cancer (RGC) sub-types and 22 projects. We perform NGS testing, depending on tumour purity, including WGS on fresh tumour samples (and on a select number of FFPE cases); we have 44 PDX models (from 35 RGC patients) which we characterize molecularly and functionally, according to standard and relevant novel therapeutics and generate 2D/3D PDX-derived models for additional drug response.
We performed WGS on 88 samples, of which 77 were RGC (69 fresh frozen, 8 FFPE). Of the 69 fresh frozen RGC examined by WGS, 30 (43%) were found to harbor highly clinically actionable information for the patient, and an additional 10 cases had information which could have provided some therapeutic direction (a total of 40 cases/69 (58%) deriving potential clinical benefit with five cases pending). Patients may not receive benefit due to disease progression whilst waiting for the result, or because of lack of drug access. For women with RGC with great unmet need, WGS has increasing potential. We describe in detail, cases demonstrating the way in which WGS impacted on patient care and improved biological understanding of RC.