NCOG-33. GLIOBLASTOMA AND PARKINSONISM, IS DEPLETED DOPAMINE A PROTECTIVE SURVIVAL FACTOR? A CASE SERIES OF 3 GBM PATIENTS

Abstract

Abstract Glioblastoma multiforme (GBM) is the most common malignant brain tumor, and carries a grave prognosis with a median survival of 15 months. The pathophysiologic hallmark of Parkinson’s disease is neuronal loss of dopamine producing cells in the substantia nigra. Dopamine has been shown to modify cell-cycle status in neural progenitor cells. Dopamine agonism is adequate to increase progenitor proliferation in the subventricular zone (SVZ). Dopamine receptor antagonists have antiproliferative effects. A few clinical trials use selective dopamine receptor D2 (DRD2) inhibitors. Parkinsonism can have organic etiologies like stroke or neoplasm, while idiopathic Parkinsonism is known as Parkinson’s disease. While uncommon to have dual diagnoses, we identified three patients with both GBM and Parkinsonism, all were IDH wildtype, 2 patients were MGMT methylated, mean age was 67 years. Our 3 patients have a combined median PFS of 23.4 months, mean PFS of 25.4 months, which compares favorably to historical control median PFS of 6.9 months. Our 3 patients with dual diagnosis have a median OS of 47.3 months, and mean OS of 43.7 months, which compares favorably to historical median OS of 14.6 months. One might expect a patient with a neurodegenerative disease like Parkinson’s disease and a highly malignant tumor like GBM to have an extremely poor prognosis, yet our patient cohort reveals the opposite. The improved overall survival in GBM patients with Parkinsonism supports further clinical research into selective dopamine receptor inhibitors.