Precision medicine directed therapy enabling long-term survival in medulloblastoma: a case report

Subgroup-SHH of medulloblastoma (MB) is primarily found in children, with an increased propensity for metastatic presentation that contributes to its poor prognosis. Current therapy approaches may include surgery, radiation, systematic chemotherapy, and autologous stem cell transplant (ASCT). At relapse, patients may receive additional chemotherapy and radiation if possible. The outcome for relapsed patients is 10-30% long term survival. Herein we present a case of a 6-year-old male with a pathologically confirmed diagnosis of subgroup-SHH MB, who was treated with upfront surgical resections, high-dose chemotherapy, and ASCT. Nine months after completion of upfront therapy, the subject relapsed. Subsequently, he was enrolled onto NMTRC009 (NCT02162732) and underwent biopsy with genomic sequencing (DNA whole exome and RNA transcriptome). A molecular tumor board, using precision medicine analysis, recommended vorinostat, vismodegib, curcumin, and palbociclib as targeted therapy. This therapy resulted in a complete tumor response and long-term survival. A cell line was derived from the subject's tumor and used for in vitro testing. Combined molecular therapies demonstrated synergistic efficacy compared with single-agent treatment.