MBRS-66. COST-EFFECTIVE METHOD TO INCORPORATE MOLECULAR CLASSIFICATION OF MEDULLOBLASTOMA INTO A LATIN-AMERICAN CLINICAL TRIAL

BACKGROUND: It is now widely accepted that medulloblastoma actually comprises four distinct molecular subgroups, requiring specific treatment strategies. Implementing routine subgrouping in a time and cost effective manner is a major challenge in Latin America, particularly the development of molecular informed clinical trials. Herein we describe the feasibility of reliable and rapid molecular stratification using a qPCR method integrated with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH – c-myc, monosomy 6) from heterogeneously fixed, low-quality FFPE samples across Latin America. RESULTS: Fifty-four FFPE samples were classified according to histologic and molecular criteria. Classic medulloblastoma was found in 53.7%, desmoplastic/extensive nodularity in 24.1%, NOS in 16,7% and anaplastic in 5,6%. IHC markers classified patients in three groups (WNT, SHH and non-WNT/non-SHH) in 98% of cases. PCR-based method confirmed results from IHC in 81,5%. Additionally, we were able to detect WNT activation in 2 patients, previously classified as SHH. For both cases, the presence of monosomy 6 further confirmed WNT subgroup. Integration of these three techniques resulted in the following frequencies: WNT (13.0%), SHH (38.9%), group 3 (9.3%), group 4 (20.3%) and non-WNT/non-SHH (18.5%). From 40 patients with clinical information available, 3-year overall survival (n=40) for low, intermediate and high-risk groups were 100%, 60% and 20%, respectively (p<0.05), based only in molecular criteria, which confirmed the prognostic importance of this method. CONCLUSIONS: At an estimated cost of $220 per patient, we are able to implement central molecular diagnosis for the incorporation into a prospective clinical trial protocol in Latin America.