Central Nervous System Tumors
Epidemiology and Etiology
Brain and other central nervous system (CNS) tumors are estimated to account for 23,890 new cancer diagnoses and 18,020 deaths in 2020.1 Risk factors include ionizing radiation and familial cancer syndromes including neurofibromatosis, tuberous sclerosis, Li-Fraumeni, and others.
Pathology
Glioblastoma is the most common subtype of primary brain tumors. Meanwhile, the World Health Organization classification further classifies CNS tumors based on histology and grade (I-IV).
Clinical Presentation
Patients with glioblastomas usually present with symptoms caused by rapid tumor expansion leading to displacement or infiltrative destruction of brain structures, progressive headaches, seizures, focal neurologic signs, and changes in mental status.
Diagnostic Testing
Workup includes MRI of the brain and molecular testing of a surgical biopsy or resected tumor specimen for methylguanine-DNA methyltransferase (MGMT) methylation, 1p#8725;19q codeletion, IDH1 mutations, and BRAF V600E activating mutations, which may help guide therapy.
TREATMENT
• The current treatment paradigm for glioblastoma is surgery with maximal safe resection followed by concurrent radiation therapy and temozolomide followed by temozolomide alone for 6 months. MGMT is a DNA repair enzyme that reverses the DNA damage caused by alkylating agents resulting in resistance to these drugs, including temozolomide. Methylation of the MGMT promoter silences the enzyme, increasing the sensitivity to alkylating drugs. The benefit from temozolomide in patients with glioblastoma is observed predominately in those with MGMT promoter methylation.30 Patients with recurrent MGMT-methylated glioblastoma may be retreated with temozolomide depending on the interval from the previous treatment.
• Other treatment options include glucocorticoids, lomustine, bevacizumab, regorafenib, and use of tumor treating fields, which employ noninvasive alternating electrical fields to disrupt tumor cell division.