Treatment Modalities

Radiation therapy is frequently used as adjunctive therapy or primary therapy. Primary therapy may be for curative intent, palliation, or stabilization. Ionizing radiation is the mainstay of treatment in neurooncology, with the most common types of radiation being photons and protons. Radiation can be delivered either in multiple treatments as “fractions” or in a single treatment dose. Advances in radiation oncology have improved its effectiveness and decreased its complications by honing its precision in an effort to minimize surrounding neurotoxicity. This has been achieved with the advent of stereotactic treatment, which is a specialized method of targeting, and the use of three-dimensional (3D) conformal treatment in which the volumetric distribution of the desired dose mimics the shape of the target. Stereotactic intensity modulated radiotherapy (IMRT) is a type of 3D conformal therapy that delivers radiation (usually photons) in a controlled and precise fashion, limiting the toxicity to the rest of the brain. Advantages include reducing the radiation dose to at-risk dose-limiting organs, such as the optic apparatus, brainstem, and inner ear, and improving dose delivery to target organs. More recently, proton beam radiation has garnered much attention because of its ability to limit the amount of scatter to normal tissue. This has allowed radiotherapists to deliver sufficient radiation to eloquent areas. Stereotactic radiosurgery (SRS), using either the linear accelerator, gamma knife, or cyber knife, delivers a large single dose of radiation in a highly focused manner, achieving a similar biologic effect as several weeks of fractionated radiation therapy. The gamma knife uses gamma radiation derived from 201 cobalt-60 sources arranged in a circular array directed at the center of the unit, where the head is rigidly fixed. A linear accelerator targets its radiation beams by rotating the patient and treatment unit gantry simultaneously. The cyber knife utilizes an image guidance system in conjunction with a linear accelerator mounted on a robotic arm. To date, a clinically meaningful advantage has not been demonstrated comparing these different approaches.

The realm of chemotherapy has also seen some advances, impacting improved overall survival and progression free survival. Temozolomide, an oral secondgeneration alkylating agent, received U.S. Food and Drug Administration (FDA) approval in 1999 for recurrent anaplastic astrocytoma, and approval in 2005 for use in newly diagnosed glioblastoma. Compared with previous alkylating agents, the adverse effects associated with temozolomide are generally mild to moderate and predictable. Moreover, the European Organisation for Research and Treatment of Cancer–National Cancer Institute of Canada (EORTC-NCIC) phase III trial demonstrated a significant improvement in survival with the addition of temozolomide to radiation, compared with radiation alone. Recently, the FDA granted accelerated approval to bevacizumab (Avastin, Genentech, South San Francisco, Calif.), a monoclonal antibody against human vascular endothelial growth factor as monotherapy for recurrent glioblastoma. Although its impact on overall survival remains modest, phase II trials have reported increased response rates and improved 6-month progression-free survival with this drug. Currently, small-molecule inhibitors are subject to much investigation as potential therapeutics for malignant glioma.

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