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Glioblastoma

  • Michael WellerEmail author
  • Colin Watts
  • David A. Reardon
  • Minesh P. Mehta
Chapter

Abstract

Glioblastoma is the most common primary parenchymal brain tumor. Its histopathological definition is based essentially on the presence of tumor cells thought to be of neuroglial origin and on the detection of neovascularization and necrosis. At the molecular level, glioblastomas are typically characterized by the absence of isocitrate dehydrogenase (IDH) 1 or 2 mutations and the presence of mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signaling. Amplifications and mutations of the epidermal growth factor receptor (EGFR) gene are found in 40% of the tumors. Giant cell glioblastoma, gliosarcoma, and epithelioid glioblastoma are morphological variants with a similar molecular profile. Gain of function mutations of the IDH 1 or 2 genes define a subgroup of patients with glioblastomas that occur at younger age and share a more favorable outcome. Histone mutations, mostly H3K27M, have been described in a subset of midline and thalamic gliomas characterized by poor prognosis. The standard of care for typical IDH wild-type glioblastoma comprises maximum safe resection as feasible followed by involved field radiotherapy with concomitant and then six cycles of maintenance temozolomide chemotherapy. Methylation of the promoter region of the DNA repair gene, O6-methylguanyl DNA methyltransferase (MGMT), predicts prolonged progression-free and overall survival for patients treated with alkylating agent chemotherapy. Testing for MGMT promoter methylation plays a particular role for selecting between radiotherapy alone and temozolomide alone for patients not considered to be eligible for combined modality treatment. Interventions at progression are more individualized, pharmacotherapy with lomustine and bevacizumab, depending on availability, being most frequently used, although survival gains with these approaches are probably small. Tumor-treating fields are a novel treatment approach based on the exposure of the affected brain region to an alternating low-voltage electrical field which has been shown to prolong survival in an open-label randomized trial in the newly diagnosed setting, but not in recurrent disease. Current topics of controversy concern the integration of tumor-treating fields into standards of care and the future role of targeted therapy and immunotherapy approaches including vaccination.

Keywords

Bevacizumab Chemotherapy Glioblastoma Immunotherapy Lomustine Radiotherapy Surgery Temozolomide 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Michael Weller
    • 1
    Email author
  • Colin Watts
    • 2
  • David A. Reardon
    • 3
  • Minesh P. Mehta
    • 4
  1. 1.Department of NeurologyUniversity Hospital and University of ZurichZurichSwitzerland
  2. 2.Institute of Cancer and Genomic SciencesUniversity of BirminghamBirminghamUK
  3. 3.Department of Medical Oncology, Center for Neuro-OncologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Miami Cancer Institute, Baptist Health of South Florida and Florida International University, Baptist HospitalMiamiUSA

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