Data from Emami et al.,57 Sklar and Constine,65 Gordon et al.,66 and Cooper et al.67

Data from Emami et al.,57 Sklar and Constine,65 Gordon et al.,66 and Cooper et al.67

brain injury; therefore, tolerance doses have been arbitrarily lowered. In clinical practice, TD 5/5 and 1/5 values of 60—65 and 50—55 Gy for partial brain irradiation and TD 5/5 and 1/5 values of 55—60 and 45—50 Gy for a limited segment of the spinal cord are commonly used. Clinical data have born out these somewhat empiric dose ranges. In a study of 203 adults with supratentorial low-grade glioma, patients were randomized to partial brain treatment fields with either 50.4 Gy in 28 fractions of 1.8 Gy each or 64.8 Gy in 36 fractions of 1.8 Gy.62 Radiation necrosis developed in 1% of patients who received 50.4 Gy and 5% of those who had 64.8 Gy. In a retrospective study of 53 head and neck cancer patients undergoing typical posterior cervical treatment fields including the cervical spinal cord to doses of 56—60 Gy in fraction sizes of <2 Gy, the incidence ofradiation myelopathy was 1.9%.63 In a subsequent study of 1048 lung cancer patients treated with thoracic radiation on three Medical Research Council Lung Cancer Working Party clinical trials, the only patients who developed radiation myelopathy were those treated with 3 Gy fractions or larger. The 2-year risk of radiation myelopathy was 2.2—2.5% among patients receiving thoracic spinal cord doses of 17 Gy in 2 fractions or 39 Gy in 13 fractions. The authors concluded that a total cord dose of 48 Gy given in 2-Gy fractions was safe.64 These data emphasize the importance of both total dose and dose per fraction in determining CNS tolerance to radiation. These concepts are implied in the neuret model of brain tolerance in which fraction size, which is related to "N" (number of fractions), is far more important than "T" (time), given that the exponent for N is much larger than that for T. The TD 5/5s given for brain and spinal cord tolerance assume a fraction size of 180—200 cGy per day. For primary CNS tumor patients being treated with curative intent, fraction size should rarely exceed 200 cGy daily, and in most situations, should be 180—200 cGy (including areas or volumes of "hot spots"). Fraction sizes greater than 200 cGy daily (usually 250—300 cGy) are commonly used for palliation of brain metastases and spinal cord compression, but only because such patients are not expected to live long enough to manifest normal tissue injury.

Table 4 shows the tolerance doses for other normal tissues of the CNS, including the brainstem, eye, ear, optic chiasm, optic nerve, and pituitary gland. The clinical manifestations of severe injury to these structures are listed.65-67

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