CUPID: Transforming Cancer of Unknown Primary with Intelligent Diagnostics

- Tissue of Origin (ToO) will be conducted on previously collected samples, A fresh biopsy will be requested only if the previous biopsy sample is inadequate to enable sufficient analysis in line with the study plan. Please note, that the above process now represents 'optimal' management of patients with advanced cancer, especially for a cancer of unknown primary, where cancer biology and site of origin remain unclear and unknown. There are no 'standard' treatment options, and the prognosis is poor. The optimal management plan (outside of research) is now supporting an approach that includes genomic profiling of the cancers as this may better guide management, improve treatment selection and improve patient outcomes. In Australia, the framework for doing such testing and analysis, with reporting of results and enacting management based on these results, remains in development. There is no 'standard process' and the reach of molecular oncology is not universal or applied in an equitable way. Our study is deigned in a manner that outlines a framework, including the development of a state-wide molecular oncology multi-disciplinary meeting, and this pathway and framework will be explored as part of the study. We are particularly keen to address the experience of Indigenous Australians within the current landscape and within the planned study framework. - Somatic tissue profiling will occur in parallel to ToO (in fact, it will be a step-wise sequence approach - with samples moving from the genomic mutation laboratory in Adelaide to the ToO testing lab in Melbourne). All the blood (1 x 9ml lithium heparin peripheral blood sample ) and biopsy samples (Sample (FFPE block) with MINIMUM 20% tumour content with minimal necrosis and 200ng DNA (send at RT)) will be collected (tissue from previous diagnostic samples) as soon as the patient is enrolled and agrees to proceed towards a detailed diagnosis. A fresh biopsy will be requested only if the previous biopsy sample is inadequate to enable sufficient analysis in line with the study plan. This is also inline with 'standard practice', as genomic profiling as such cancers is now considered 'best practice', where genomic testing is available. - The genomic pathology testing and reporting will be conducted by specialist genomic pathologists. The specialist pathologists involved in the research are experienced at detecting the known actionable mutations. Another group of specialist pathologists will perform the tissue of origin testing, and will provide a report based on the test results. These pathologists have worked on ToO testing, and have published their results. They will continue this research as part of our study, hoping to validate previous findings. Together, all specialist pathologists and the involved medical oncologists and other treating specialists will meet through the 'Molecular MDT' to discuss the results and consider the implications of the findings with respect to patient management. This process will be studied as part of the planned research. - The anticipated time needed to obtain the results of the genomic testing is between 4-8 weeks post tissue collection. Patients will not be expected to wait for these results. Patients are expected to commence 'standard therapy' in the absence of knowing the results from the planned genomic tests. The results, however, may guide subsequent therapy. In selected cases, and if this meets with the patient's preference, treatment may be commenced after the genomic results are available. The above sequence and process outlines what is rapidly becoming an 'optimal' and 'standard' clinical care pathway, not a 'research pathway'. Our research intends to examine this pathway, -The aspects of Optimal care pathway will be assessed by the following steps: 1. Prevention and early detection 2. Presentation, initial investigations and referral 3. Diagnosis, staging and treatment planning 4. Treatment 5. Care after initial treatment and recovery 6. Managing recurrent or progressive disease 7. End-of-life care". - Compliance assessments will be conducted by assigned research staff. These staff members will have access to clinical records. -The assessment will be carried out via a checklist extracted from OCP and compared with Sunrise EMR/medical records whether the pathway/steps were followed as per OCP or not. -The OCP will be implemented in parallel to the ToO and Somatic mutation profiling. as per OCP at step 2 when CUP specific sub-set and CUP non-specific sub-set patients will be referred to oncologist, progressing on to step 3; further diagnostic workup following ToO and Somatic mutation profiling will come in place to match targeted therapies to actionable mutations. In other words, the OCP will be assessed along the entire patient care continuum.