Advances in Treatment Options for High-grade Glioma – Current Status and Future Perspectives

European Neurological Review, 2010;5(1):49-55 DOI: http://doi.org/10.17925/ENR.2010.05.01.49

Abstract:

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumours diagnosed in adults. The prognosis for these tumours is poor despite multimodality therapy with surgery, radiation and/or chemotherapy. This review summarises treatment options for high-grade glioma, including standard regimens, targeted agents and novel therapies.
Acknowledgement: The authors gratefully acknowledge the support of the Jim Kenary Brain Tumor Research Fund.
Keywords: High-grade glioma, radiation therapy, chemotherapy, targeted molecular therapies
Disclosure: Ryan T Merrell and Eudocia C Quant have no conflicts of interest to declare. Patrick Y Wen has received research support from Amgen, Novartis, AstraZeneca, Exelixis, Boehringer-Ingelheim and Schering-Plough and is a member of advisory boards for Esai, Angiochem and Genentech.
Received: May 26, 2010 Accepted June 30, 2010
Correspondence: Patrick Y Wen, Center for Neuro-oncology, Dana Farber/Brigham and Women’s Cancer Center, SW430, 44 Binney Street, Boston, MA 02115, US. E: pwen@partners.org

High-grade glioma (HGG) is the most common type of primary brain tumour in adults and accounts for >75% of the estimated 22,070 newly diagnosed malignant primary brain tumours in the US each year.1 More than half of HGGs are glioblastoma (GBM), the most aggressive subtype. The remainder include anaplastic gliomas (AGs),1,2 such as anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), and rarer subtypes. HGG is incurable and is responsible for a disproportionate share of cancer-related morbidity and mortality.3 With optimal treatment, median survival is only 12–18 months for GBM and two to five years for AG. There have been recent advances in elucidating the molecular pathogenesis of HGG, which may provide additional prognostic information and lead to more effective treatments.4–10 This article summarises the standard treatment of adult HGG with a particular focus on recent therapeutic advances.

Standard Treatment Options for High-grade Glioma
Surgery for High-grade Glioma

Maximal surgical resection is recommended in all newly diagnosed HGG patients. Although a surgical cure is impossible, benefits of resection include improvement of symptoms related to mass effect, reduction of tumour volume11 and removal of the necrotic tumour core, which may be resistant to radiation therapy and poorly accessible to circulating chemotherapy. Mounting evidence suggests that a near gross total resection confers a modest survival benefit compared with biopsy or subtotal resection.12–14

Surgery may be considered in recurrent HGG patients with good performance status when the tumour is accessible, symptomatic and distant from eloquent areas. Surgical resection in the recurrent setting may improve quality of life and allow time for additional therapy, but the impact on overall survival is negligible.

Radiation Therapy for High-grade Glioma

Radiation therapy (RT) has the biggest impact on overall survival for HGG of all standard treatment modalities. The addition of RT to surgery for glioblastoma (GBM) increases median survival from three to four months to approximately 12 months.15,16

Many variations of standard RT have been investigated in an attempt to increase efficacy, including using doses >60Gy, altered fractionation schemes, brachytherapy, stereotactic radiosurgery (SRS) and the use of radiosensitising agents. None of these has demonstrated additional benefit over standard fractionated RT.17,18 Newer approaches including chemotherapy,19 targeted molecular agents20 and anti-angiogenic agents21 may potentially work synergistically with RT and improve outcomes.

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Keywords: High-grade glioma, radiation therapy, chemotherapy, targeted molecular therapies