European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH).

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

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.

Thyrotropin-secreting pituitary adenomas: outcome of pituitary surgery and irradiation.

OBJECTIVE: Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tumor mass in short- and long-term follow-up of TSH-secreting pituitary adenomas (TSHomas). METHODS: This was a retrospective multicenter study. RESULTS: We collected data of 70 TSHomas (70% macroadenomas). The mean follow-up was 64.4 (range 3-324) months. Overall, 97% of patients were treated with surgery; in 27% of them radiotherapy was associated. After surgery, 75% of patients normalized thyroid function, 58% normalized both pituitary imaging and hormonal profile, 9% developed pituitary deficiencies, and 3% had tumor or hormonal recurrence, all within the first 2 years after surgery. Presurgical medical treatment did not significantly improve surgical outcome (63% vs 57%). Radiotherapy controlled hypersecretion in 37% of patients within 2 years, whereas 32% of patients developed new pituitary deficiencies from 18 to 96 months from treatment. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment: 85% with somatostatin analog (SSA) alone and 15% with SSA combined with methimazole. Subjects who achieved disease control had surgery as the only treatment in 80% of cases and surgery combined with irradiation in 20%. CONCLUSIONS: Surgery remains the first-choice treatment for TSHoma. If surgery is successful, recurrence is rare. When surgery is unsuccessful or contraindicated, SSA and radiotherapy are effective in controlling hyperthyroidism and tumor growth in the majority of patients. The effects of radiotherapy on TSH secretion and tumor mass are greater within the first years after treatment, whereas pituitary deficiencies may occur several years later.

Targeting and conformality in arteriovenous malformation radiosurgery.

The struggle to achieve a high degree of conformity around targets of complex morphology has been one of the driving forces in the development of ever more sophisticated radiosurgical devices and intricate treatment delivery. Rarely are radiosurgical targets more complex in shape than those associated with arteriovenous malformations (AVMs). In this report we examine theoretical and practical issues of target delineation and creation of conformal AVM treatment plans, and comment on the concepts of gradient and homogeneity.

Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.

BACKGROUND: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE: To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS: Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.