Radiation Therapy

Pituitary radiation has been used for more than 50 yr, usually as adjunctive therapy after surgery. Conventional or fractionated radiation given during 4 to 5 wk requires 10 to 20 yr to be effective. Stereotactic or focused radiation allows for precise delivery of radiation to a circumscribed area, with reduction in the amount of radiation to the brain; more focused methods of radiation delivery include the Gamma Knife, LINEAC, and proton beam. The widely quoted study in 1979 from the National Institutes of Health (NIH) reported on 47 patients treated with fractionated radiotherapy as primary treatment found that serum GH levels were reduced to <5 ng/mL (^g/L) (13 mU/L) in 67% of patients within 10 yr of treatment (30). Considering what is now known about the importance of lowering GH (and presumably IGF-1) levels to normal to reduce the risk of premature death, all efforts should be made to recommend treatment that has the best chance of accomplishing this goal. Thus, pituitary radiation should be reserved for patients who have residual disease after surgery. Because it usually requires months to years for radiation to be effective in lowering GH and IGF-1 to normal, patients should be given medical therapy when awaiting the thera peutic effect of radiation. The conventional method of administering pituitary radiation is delivery through 3 ports (bitemporal and frontal) in fractions during 4 to 5 wk. Other methods include particle beam (protons, deuterons, helium ions), usually administered in 4 fractions during 5 d, or the more recently developed stereotactic methods, Gamma Knife, and LINEAC. Particle beam radiotherapy in 220 patients with acromegaly lowered the median GH level to 5 ng/ mL (^g/L) (13 mU/L) or less 4 yr after treatment in 169 patients (77%). Another study of 114 patients treated with helium ion radiotherapy resulted in lowered fasting GH to 5 ng/mL (^g/L) (13 mUu/L) or less 7 yr after treatment in 26 patients (23%) (31). Stereotactic radiation with the Gamma Knife involves delivery of focused radiation through 201 ports, usually in one treatment. The theoretical advantage of this method is minimal exposure of brain tissue to radiation, the ability to treat a very circumscribed area and with minimal exposure to the hypothalamus and optic chiasm. This method is best reserved for patients with a small amount of residual tumor that is not close to the optic chiasm. Gamma Knife radiotherapy in 20 patients resulted in reduction in fasting GH to <2.5 ng/mL (^g/L) in 7 (35%) 6 mo to 7 yr after treatment (32). Using MRI planning, 56 patients with acromegaly were given postoperative Gamma Knife radiotherapy; 36 were followed for >6 mo of whom 25% (9 out of 36) achieved a normal serum IGF-1 5 to 43 mo after treatment (average 20 mo) (33). It is important to note that the technique of planning the radiation field for the Gamma Knife has advanced throughout the years, from the less precise use of pneumoen-cephalography to the computer tomography (CT) scan to the current use of MRI planning. Comparison of results among studies using different techniques is difficult given radiation delivery methods and the evolution of the criterion for cure.

Anticipated complications of radiation include development of hypopituitar-ism. Deficiency of some or all of the pituitary hormones usually occurs in a progressive fashion, the earliest and most common deficiency is that of the gonadotropins (luteinizing hormone [LH], follicle-stimulating hormone [FSH]) with consequent gonadal failure (34). Development of GH deficiency in these patients has not been studied systematically. In 35 patients treated with conventional radiotherapy, adenocortictropic hormone (ACTH) deficiency developed in 67%, thyroid-stimulating hormone (TSH) deficiency in 55%, and gonadotropin deficiency in 67% after a mean follow-up of 4.2 yr (35).

Patients who receive pituitary radiation should be followed regularly (at least every 6 mo) with appropriate hormone measurements and prompt institution of replacement therapy as indicated. The risk of developing a CNS malignancy is low but is a consideration. Prospective studies detailing intellectual function before and after radiotherapy are not available. The incidence of pituitary failure after stereotactic radiation (Gamma Knife, LINEAC, proton beam) is not as well established. Prospective follow up of these patients is necessary.

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