Therapeutic Radiology

Radiation therapy is commonly used to treat brain tumors. Some, such as germinomas can be cured and others such as malignant gliomas are slowed in their progression. The target for radiation-induced cell death is the genetic information within the cell, the DNA molecule. High-energy beams cause breaks in the DNA. The effect of radiation depends on the dose applied, how often it is applied and how much time is available for the target to repair the damage. Dividing cells (such as tumor cells) are more susceptible to irradiation than non-dividing cells.

Photons are the most commonly used particles in the radiotherapy of brain tumors. Examples for non-photon irradiation modalities (available in experimental facilities) are neutrons, protons, helium ions, pions and heavy ions (carbon, argon, neon).

External beam radiation therapy

Most commonly radiation therapy is provided by a machine called linear accelerator (LINAC), which uses high-frequency electromagnetic waves to accelerate electrons to high energies. Shielding blocks are built for each patient to restrict the beam to the tumor. The size of the treatment field depends on the tumor type. For tumors that tend to infiltrate the adjacent normal brain such as malignant gliomas therapy is provided to the tumor as seen on MRI and a margin of 1-3 cm. Other tumor types (multiple brain metastases) require whole brain radiation therapy. Numerous strategies, mainly of experimental nature, have been developed to improve tumor cell kill and minimize damage to normal tissue. These include increasing the number of treatment fractions to two or more per day (thereby reducing the time for tumor repair of damage), the use of multiple fields (to diminish damage to normal tissue; ‘3-D conformal radiation therapy’), the use of radiosensitizing agents, or localized high field strength sources (brachytherapy or radiosurgery).

Conventional fractionated radiotherapy

Conventional radiation therapy is given in daily fractions (except weekends). For malignant gliomas, treatment lasts six weeks. Dividing the total radiation dose in 30 treatments (‘fractions’) requires immobilization devices such as bite blocks and Thermoplast molds that allow reproducible positioning of the patient with each treatment. The use of multiple radiation fields or 3-dimensional conformal irradiation limits the exposure of overlying skin and normal brain tissue.

Brachytherapy

In Brachytherapy, radiation is delivered by implanting the irradiation source close to or into the target tissue. This type of therapy uses iridium-192 or iodine-125 seeds. For malignant gliomas, this type of therapy has not been of benefit to patients and is currently not performed at the Yale Brain Tumor Center. Intratumoral positioning of miniature x-ray generating devices or application of radiation-emitting substances are other forms of local radiation delivery. The latter form is currently used in a clinical trial for patients with brain metastases at Yale.

Sensitization of tumor cells to ionizing radiation

Hypoxic tumor cells can evade the lethal effect of irradiation. Rapidly growing tumors such as malignant gliomas contain a large number of hypoxic cells. These cells can be manipulated through pharmacologic strategies. Clinical trials with radiosensitizng agents are ongoing. Examples are hydroxyurea, thalidomide and Suramine.

Stereotactic Radiosurgery Techniques

Radiosurgery delivers large doses of radiation to well circumscribed tumor sites while minimizing exposure to normal tissue. Three facilities exist: gamma knife, LINAC and proton beam radiosurgery. Gamma knife radiosurgery – available at Yale - provides irradiation using 200 separate sources in a hemispherical array aimed at the target tumor. The procedure is painless and free of surgical complications such as infection and hemorrhage. The precision of this technique spares important parts of the brain that have historically been subject to injury with conventional radiation therapy. Indications at present include:

• Benign tumors such as meningiomas, acoustic neuromas, pituitary adenomas and craniopharyngiomas
• Selected cases of primary or recurrent malignant brain tumors such as astrocytomas or oligodendrogliomas
• Solitary and multiple brain metastases
• Head and neck tumors such as nasopharyngeal carcinomas and ocular melanomas
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Intractable pain secondary to cancer
• Movement disorders such as Parkinson's disease and essential tumor

Since Gamma Knife radiosurgery requires no incisions and is performed under local anesthesia with mild sedation, the risks of infections and adverse reactions to general anesthesia are eliminated. Patients experience minimal pain and are therefore able to return to their former activities without discomfort or restrictions. Hospitalization is either minimized or not required. Because only the target tissue is irradiated, sparing the surrounding brain, hair loss is eliminated and secondary reactions such as nausea and epileptic seizures are minimized. Finally, the accumulated experience of over 30 years of treatment using the Gamma Knife allows for predictable outcomes with a high degree of accuracy.

LINAC radiosurgery uses a modified linear accelerator to produce high-energy photon beams. Heavy charged particle beams such as helium or protons (Proton Radiosurgery) offer optimal physical characteristics for stereotactic applications. The technique is only available in very few centers in the United States. These radiosurgery techniques require 'immobilization masks', rigid frames affixed to the patient's skull or fitted mouthpieces.