Stereotactic Radiosurgery in the Management of Brain Metastasis

Michael L. Smith, M.D.; John Y. K. Lee, M.D.

Disclosures

Neurosurg Focus. 2007;22(3) 

In This Article

Dose and Tumor Size

Radiation dosing is usually described in terms of Gy delivered to the prescription isodose line. This allows a simple understanding of the minimum amount of radiation delivered to every tumor cell. The prescription dose refers to the radiation dose, usually specified in Gy or cGy, delivered to the tumor margin. Hence, the general goal is to include the entire gross tumor volume within the prescribed tumor volume. The prescription dose is often referenced as a percentage of the maximum dose (Fig. 1). To achieve effective local control and the survival benefit of SRS requires the delivery of a tumoricidal radiation dose to all neoplastic cells within the prescription dose line while minimizing the radiation dose to the surrounding brain parenchyma. Modern SRS systems can contour isodoses to the tumor volume precisely, but large tumor volumes present difficulties. A large tumor volume results in a higher integral radiation dose to the surrounding brain. Thus, larger tumors must generally be treated with a lower dosage in order to avoid radiation toxicity.[46] Because of the corresponding decrease in dose, the ability to achieve local control may be compromised.

Figure 1.

Screen snapshot from planning software showing targeting of a left thalamic enhancing mass in a patient with metastatic melanoma. Two prescription isodose curves show 50% (yellow) and 35% (green).

Dose escalation studies conducted by the RTOG outlined maximum tolerated doses in patients undergoing SRS after WBRT or fractionated external-beam radiation.[46] The study population included patients with primary gliomas and brain metastases and was not subdivided. The primary stratification variable was size. The tumors were divided into groups of less than 2 cm, 2 to 3 cm, or 3 to 4 cm ( Table 2 ). The maximum tolerated dose was not reached for tumors larger than 2 cm. This study provides a guideline for dosing but does not account for other variables, such as location of delivery. For example, the optic nerve and brainstem are more sensitive to radiation-induced edema than the frontal lobe.[19] The dose prescription must be reduced if necessary to protect such structures. Clinical judgment and experience remain important in dose prescription.

The authors of several studies have demonstrated differences in local tumor control based on size. One study demonstrated a 78% response rate in tumors 2 cm3 or smaller compared with a 50% response rate in tumors 10 cm3 or greater.[22] In a study of 103 patients with melanoma metastases, local control rates after SRS were 75.2% for lesions less than 2 cm in diameter compared with 42.3% in larger lesions.[45] The same authors studied another 135 patients with tumors of various histological types and found local 1- and 2-year control rates of 86 and 78% for tumors less than 1 cm in diameter compared with 56 and 24% for tumors of larger diameters.[9] A systematic analysis of this topic comes from a recent publication in which the established dosing schedule outlined by RTOG 90-05 was used.[53] A three-part grouping of 1-year local control rates based on size is presented in Table 2 .

Local control has been used as a surrogate end point in some trials[24] but does not necessarily correlate with survival. Two studies found no significant effect of tumor size on survival,[18,48] whereas another found it to be the most important factor predicting survival.[49]

The size of the brain metastasis must influence the choice of treatment modality. Local control of larger tumors with SRS is compromised because of the need to limit the prescription dose. Larger tumors with mass effect, especially if single and superficial, should be resected if the patient is young, has good systemic disease control, and a high KPS score. Tumors that are small, multiple, deep, or that have a minimal mass effect should be managed with SRS. Clinical judgment and patient preference must help guide treatment decisions for the many patients with conditions between the two extremes.[39]

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