Angi-07. glioblastoma with bony metastatic disease in a patient with neurofibromatosis type 1: a case report

Abstract Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor predisposition syndrome causing diffuse neurofibromas, plexiform neurofibromas, and in a minority of patients malignant peripheral nerve sheath tumors (MPNST) and gliomas. Gliomas from NF1 typically present early in life and can be grade 1-4, with higher grades less frequent. Malignant gliomas associated with NF1 have a different molecular landscape compared to sporadic gliomas. Extracranial spread of gliomas is extremely rare for reasons unknown, but renal transplants from gliomas patients have resulted in clonal gliomas in organ recipients. We present here the first reported case of extracranial metastases of GBM to bone in a 21 year old male with NF1. At the age of 18, he was diagnosed with a high-grade astrocytoma consistent with GBM (IDH wildtype, MGMT unmethylated). This was 2 years following a diagnosis of a right neck plexiform neurofibroma. His GBM was initially treated with six cycles of temozolomide. Following temozolomide he underwent another resection (1.5 years after initial surgery) due to tumor recurrence. Resection was followed by proton radiation therapy and selumetinib, a MEK inhibitor approved for treatment of plexiform neurofibromas in NF1. The selumetinib did reduce his plexiform neurofibroma, but did not have an apparent effect on his GBM. Selumetinib was stopped five months after initiation due to increased tumor burden and he began lomustine, followed by bevacizumab and etoposide at next recurrence. About 2.5 years after his initial GBM diagnosis, he had low back pain and imaging showed multiple sites of bony metastases. Pathology confirmed extracranial spread of GBM.