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Gamma-Knife Radiosurgery in Acromegaly: A 4-Year Follow-Up Study

Division of Endocrinology, Ospedale Niguarda (R.A., R.C., P.L.); Institute of Endocrine Sciences (P.E., P.B.-P., M.A.) and Department of Neurological Sciences and Neurosurgery (E.M.), University of Milan; Unit of Endocrinology, Ospedale San Giuseppe-Fatebenefratelli, A.Fa.R., (P.E., M.A.); and Neuroradiology Unit, Ospedale Maggiore IRCCS (M.F.), 20100 Milan, Italy; and Department of Neurosurgery-Gamma Knife, Villa Maria Cecilia Hospital (E.G., L.V.), 48010 Cotignola, Ravenna, Italy

Address all correspondence and requests for reprints to: Maura Arosio, M.D., Institute of Endocrine Sciences, University of Milan, Ospedale S. Giuseppe, U.O. Endocrinologia, via S. Vittore 12, I-20123 Milan, Italy. E-mail: maura.arosio{at}unimi.it.

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3–11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15–35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9–96), IGF-I fell from 805 µg/liter (median; interquartile range, 640–994) to 460 µg/liter (interquartile range, 217–654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 µg/liter (interquartile range, 6.4–15) to 2.9 µg/liter (interquartile range, 2–5.3; P < 0.0001), reaching levels below 2.5 µg/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20–3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12–36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.

Abbreviations: GK, Gamma-knife; IFMA, immunofluorometric assay; RT, radiotherapy; SA, somatostatin analog; UFC, urinary free cortisol.

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