Radiation

Radiotherapy is indicated for almost all patients with cerebral metastasis. The optimal method of delivery, dose and regimen varies with the individual patient. In many cases, these are controversial. Radiation can be administered either as fractionated external radiotherapy to the whole brain (WBRT), the region of the tumor (local fractionated radiotherapy) or both (WBRT with a local boost), as single exposure radiosurgery or as interstitial brachytherapy.

Fractionated whole-brain radiotherapy has been the standard treatment for brain metastases for almost half a century. WBRT increases the median duration of survival of patients to 3-6 months from 1-2 months (10-15% survive for at least 1 year) [7,9]. Treatment improves neurologic function in 50-75% of patients [9]. Large retrospective studies reveal that 50% of the patients treated with WBRT die from systemic cancer, rather than from progressive brain disease. The dosing regimen most commonly employed is 30 Gy over 2 weeks in ten daily 3.0 Gy fractions. This regimen is as effective as those with higher doses or more extended fractionation.

Prognostic factors favoring survival include age less than 60 years, Karnofsky performance score of at least 70, control of the primary tumor and absence of extracranial metastases. Radiation cell sensitizers such as nitroimida-zoles are not beneficial. Although certain types of tumor, such as renal cell carcinoma and melanoma, are relatively radioresistant, the duration of patient survival following radiotherapy of cerebral metastases is similar for most tumor types [9].

Radiation therapy has significant risk of acute and long-term complications. Acutely, fatigue, headache, nausea and vomiting may occur during and shortly after treatment and neurologic deficits may be exacerbated. Steroid therapy is often required. Chronically, side effects, such as dementia, ataxia and urinary incontinence, occur in at least 5% of patients who survive longer than 1 year [10]. In one study, 50% of patients surviving for more than 2 years after surgical resection and WBRT developed leukoencephalopathy or atrophy-induced hydrocephalus ex vacuo. More prolonged fractionation schemes and more focal treatment are strategies designed to decrease the risk of dementia. Patients expected to survive longer than 6-12 months are often treated with 40 Gy in 2 -Gy fractions over 4 weeks. In an attempt to spare normal brain, fractionated local radiotherapy has been used for single metastases, but the relative effectiveness of focal and whole-brain therapy has not been studied. Additional local dose can also be administered as a boost to the lesion following WBRT.

Radiosurgery involves single-session highdose irradiation of a stereotactically defined target. In that radiosurgery intends inactivation of all tissue within a targeted volume, it is a non-invasive alternative to surgical excision. Multiple techniques (Linac, Gamma Knife, Cyber Knife, and Proton Beam) are able to deliver the conformal radiation required. Since the likelihood of controlling tumor growth and the risk of radiation injury to surrounding tissue both increase with increasing dose and the risk of radiation injury increases with increasing target volume, there is an interdependence of tumor volume, dose, tumor control rate and complication rate. Empirically defined relationships specify an inverse relationship between two variables (e.g. tumor size and dose) after two parameters have been established (e.g. minimal acceptable rate of tumor control and maximal acceptable rate of complication). For example, if one posits that at least 15 Gy is required to achieve a 90% rate of tumor control at 1 year and that the acceptable risk of complication is 1%, then the maximal tumor volume that can be safely and effectively treated is 10 cm3. In other words, given such specifications for safety and efficacy, there is an ideal dose for each tumor volume. In general, stereotactic radiosurgery is an effective treatment for intra-cranial metastases of less than 10 cm3 in volume (2.5-3.0 cm in diameter).

Radiosurgery is indicated for surgically inaccessible lesions and is an acceptable alternative to surgery for many accessible ones. Although

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