Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10-year follow-up study.

OBJECTIVE: The long-term efficacy and safety of stereotactic radiosurgery by gamma knife (GK) still remain unknown. The aim of the study was to investigate the long-term efficacy and tolerability of GK in acromegalic patients. DESIGN AND PATIENTS: Retrospective analysis for a median follow-up of 10 years. Thirty-five acromegalic patients from two referral centres in Milan submitted to GK (median margin dose: 20 Gy, median % isodose: 50) between 1995 and 2004. MAIN OUTCOME MEASURES: GH/IGF-I secretion, anterior pituitary function, radiological imaging and ophthalmological data. RESULTS: Cure rate improved over time (up to 46% at 10 years), as did the proportion of patients achieving control on somatostatin analogues (from 12.5% at baseline to 50% at 10 years). Normal IGF-I values were observed in 82% of patients at their last visit. No visual impairment, disease recurrence, tumour growth or secondary cerebral tumour occurred. Half of the patients developed one or more new deficiencies, while two patients normalized their prior failures. In particular, new onset of clinical or subclinical hypoadrenalism occurred in 12/30 patients (40%), hypothyroidism in 3/28 (11%), hypogonadism in 2/15 (13%) and GH deficiency in 2/35 (6%). GH value at the time of GK was the best negative predictor of cure and margin dose was the best positive predictor of new hypopituitarism. CONCLUSIONS: Over a 10-year period after GK radiosurgery, an increasing percentage of patients achieve cure, or adequate control of the disease on pharmacological therapy, at the expense of increasing novel pituitary deficiencies.

Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study.

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 micro g/liter (median; interquartile range, 640-994) to 460 micro g/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 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/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.

Hearing loss and changes in transient evoked otoacoustic emissions after gamma knife radiosurgery for acoustic neurinomas.

OBJECTIVE: To evaluate the neuro-otological effects of gamma knife radiosurgery in patients with acoustic neurinoma. DESIGN: Prospective study. SETTING: University hospital in Milan, Italy. PATIENTS: Thirty consecutive patients with acoustic neurinoma who underwent gamma knife radiosurgery. INTERVENTION: Gamma knife radiosurgery. MAIN OUTCOME MEASURES: Results of neuro-otological tests, including pure-tone audiometry, auditory brainstem responses, and transient evoked otoacoustic emissions, during a 2-year follow-up. RESULTS: Three patients showed slight tumor growth, 1 complained of a transient facial disturbance, and 5 complained of mild trigeminal disturbances. Seven of the 26 patients with a measurable threshold before radiosurgery experienced a 2-year decrease of more than 20 dB in at least 1 hearing level, and 2 of these became deaf in the affected ear. The analysis of auditory brainstem responses showed no significant increase in mean wave V latency after radiosurgery, but intensity of transient evoked otoacoustic emissions worsened in 9 of the 12 patients who had them before treatment. A statistically significant correlation was found between the 2-year decrease in low-tone average, pure-tone average, and high-tone average hearing levels and the 2-year decrease in transient evoked oacoustic emissions (P<.001, P =.008, and P<.001, respectively), and between the 2-year decrease in high-tone average hearing and the maximal cochlear dose (P =.03). CONCLUSIONS: Although most patients had only a slight fluctuation of their hearing threshold after gamma knife radiosurgery, several experienced a remarkable hearing worsening. Hearing impairment was found to be mainly due to cochlear irradiation and maximal cochlear dose, which was correlated to hearing loss.