Dei-02. Direct Patient Outreach in Pediatric Neuro-Oncology to Improve Access to Genomic Profiling – The Make-an-Impact Program

Abstract BACKGROUND Genomic profiling and precision medicine have revolutionized cancer care but are not accessible to all due to high costs, insurance issues, limited access to testing facilities or qualified personnel. We established a program providing free clinical genomic testing worldwide (Make-An-IMPACT) and report findings from the pediatric CNS tumor cohort. METHODS Following a referral from: (1) a physician, (2) a disease-specific advocacy group, or (3) submission of contact information through program website, patients were enrolled on an IRB-approved protocol (NCT01775072). CSF cell free DNA (cfDNA) and matched normal samples were analyzed using MSK-IMPACTTM, a New York State Department of Health authorized hybridization capture-based next-generation panel DNA sequencing clinical assay. If a driver mutation wasn’t reported, raw genomic data was reviewed. OncoKBTM was used to determine the level of evidence supporting the clinical actionability of genomic aberrations. RESULTS 24 patients (median age 7.5; range 0.1-20 years) were enrolled; 9 (38%) from 5 non-US countries and 6 (25%) from non-NYC US sites. African American and Hispanics constituted 8% and 13% of the cohort. Potentially actionable alterations were identified in 4/24 (17%) cases; 2/24 (8%) subsequently received matched therapy. In unbiopsied or non-diagnostic cases, a disease defining alteration was identified in 8/15 (53.3%). BRAF-KIAA1549 fusions were identified in 2/3 DLGNT patients and 1p loss in all 3. Both patients with BRAF fused DLGNT started targeted therapy with Trametinib, one of whom achieved a durable treatment response for 2.5 years. 3/8 patients with unbiopsied brainstem lesions had a H3.3K27M mutation, while 2 had non-H3.3K27M mutations detected (1 SMARCB1 deletion, 1 IDHR172G mutation) leading to treatment regimen changes. CONCLUSIONS This study captured a broad range of pediatric CNS malignancies with a diverse patient representation across geographic regions. CSF cfDNA profiling provided important diagnostic and therapeutic information reported in real time to patients and local physicians.