Study Objectives Describe the purpose, specific aims or objectives. State the hypotheses to be tested. 1.Establish the feasibility of sample procurement, central pathology review, and central processing of methylation profile for 750 samples from 7 centers over 24 months. 2.Determine the percentage of cases in which a clinically-important change in diagnosis is made based on the methylation profile. 3.Based on 2 common clinical entities (high-grade gliomas and meningiomas), assess the cost-effectiveness of methylation profiling.
Primary Study Endpoints Feasibility: Currently 8 cases can be processed per array. Up to 48 samples can be processed in one batch comfortably, and up to a maximum of 96 samples can be processed in one week. The turnaround time is minimum 1 week as soon as at least 8 samples are collected for processing.
It is conceivable that there will be periods wherein we will not have 8 samples at a time to process an array, resulting in a delay in the methylation profile reporting. This limitation has formed the basis of this objective. Thus, to establish feasibility and clinical relevance of sample procurement for clinical utility, we will collect the following data:
Secondary Study Endpoints Clinically-important change in diagnosis: Management of people with nervous system tumors is comprised of not only interventions but also diagnostic strategies. Therefore, in addition to change in surgical approach/radiation therapy plan/chemotherapy type or schedule, if the clinical team opts for a different diagnostic approach (initiating additional molecular testing, changing type of imaging or laboratory tests, changing the frequency or imaging/ laboratory/ or clinical follow-up), based on the methylation results, then this will be considered a meaningful change in management. This will be recorded and collectively analyzed at the conclusion of the study. We expect that the proportion of cases in which a change in management will result from the methylation profile will be within the 12-15% reported based on prior results for challenging nervous system tumors.2,3
