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Introduction: Persistent growth hormone hypersecretion can be observed in roughly 50% of patients operated for somatotroph adenomas, requiring additional treatments. Despite its proven antisecretory efficacy, the use of Gamma Knife radiosurgery (GK) is limited probably due to the lack of data on long-term side effects, including potential cognitive consequences., Methods: The LATe Effects of Radiosurgery in Acromegaly study was a cross-sectional exposed/unexposed non-randomized study. The primary objective was to determine the long-term neurocognitive effects of GK focusing on memory, executive functions, and calculation ability. Exposed patients had been treated by GK for acromegaly at least 5 years before inclusion. Unexposed patients (paired for age) had to be cured or controlled at last follow-up without any radiation technique. Patients of both groups were cured or controlled at the last follow-up., Results: Sixty-four patients were evaluated (27 exposed and 37 unexposed). Mean follow-up after GK was 13 ± 6 years (including 24 patients followed for at least 10 years). While up to 23.8% of the patients of the whole cohort presented at least one abnormal cognitive test, we did not observe any significant difference in neurocognitive function between both groups. During the follow-up, 11 patients presented at least one new pituitary deficiency (P = 0.009 for thyroid-stimulating hormone deficiency with a higher rate in exposed patients), two presented a stroke (1 in each group), and one presented a meningioma (12 years after GK)., Conclusions: While GK exposes patients to a well-known risk of pituitary deficiency, it does not seem to induce long-term cognitive consequences in patients treated for acromegaly.

Background: Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications., Objective: To assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action., Methods: The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants will be randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary GammaKnife (Elekta, Stockholm, Sweden) radiosurgery (160 Gy delivered in pituitary gland) associated with standards of care. Evaluation assessments will be taken at baseline, day0, day4, day7, day14, day28, day45, month3, and month6., Expected Outcomes: We could expect pain improvement in 70% to 90% of cases at day4. In addition we will assess the safety of pituitary radiosurgery in a vulnerable population. The secondary endpoints could show decay of opioid consumption, good patient satisfaction, and improvement of the quality of life., Discussion: The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. New recommendations could be obtained in order to improve pain relief and quality of life.

Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamartoma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients with hypothalamic hamartoma (HH) were followed prospectively at the Department of Endocrinology, La Timone Hospital, Marseille, France, for a mean follow-up of >2 years (mean ± standard deviation [SD] 3.6 ± 2 years). Initial pre- and post-GK radiosurgery evaluations were performed, including weight, body mass index (BMI), and a complete endocrinological workup. At diagnosis, eight patients presented with central precocious puberty at a mean age of 5.4 ± 2.4 years. At the time of GK (mean age 18.2 ± 11.1 years), two patients previously treated with surgery presented with luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency. After GK, only one patient presented with a new thyrotropin-stimulating hormone (TSH) deficiency, 2 years after the procedure. The other pituitary axes remained normal in all but two patients (who had LH/FSH deficiency prior to GK). There was no significant difference between pre- and post-GK mean BMI (26.9 vs. 25.1 kg/m 2 , p = 0.59). To conclude, in this group of 34 patients, GK did not induce major endocrinologic side effects reported with all the other surgical techniques in the literature. It is, thus, a safe and effective procedure in the treatment of hypothalamic hamartoma., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Trans-sphenoidal neurosurgery is the gold standard treatment for pituitary adenomas, but it can be contraindicated or ineffective. Stereotactic radiosurgery is a procedure aimed at controlling hormone hypersecretion and tumor size of pituitary adenomas. This Review discusses the long-term efficacy and adverse effects of stereotactic radiosurgery with the Gamma Knife((R)) in secreting and nonsecreting pituitary adenomas. Long-term data confirm the antisecretory efficacy of the procedure (about 50% remission in hypersecreting tumors) but also a previously unknown low risk of recurrence (2-10% of cases). The time to remission is estimated to range from 12 to 60 months. The antitumoral efficacy of this treatment against nonsecreting tumors is observed in about 90% of cases. Hypopituitarism is the main adverse effect, observed in 20-40% of cases. Comparisons with conventional fractionated radiotherapy reveal a lower rate of remission with Gamma Knife((R)) radiosurgery, counterbalanced by a more rapid efficacy and a lower rate of hypopituitarism. Short-term follow-up results on stereotactic fractionated radiotherapy suggest a risk of hypopituitarism similar to the one observed with radiosurgery. Therefore, stereotactic radiosurgery is probably still useful to treat some cases of pituitary adenoma, despite the fact that antisecretory drugs, particularly for acromegaly and prolactinomas, are becoming more effective and are well tolerated, thus increasing the probability of success with nonsurgical therapy.

Context: To date, no study reported long-term follow-up results of gamma knife stereotactic radiosurgery (SR)., Objective: The aim of the study was to determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas., Design: We conducted a retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up of at least 60 months., Patients: A total of 76 patients were treated by SR for acromegaly (n = 43), Cushing's disease (CD; n = 18), or prolactinoma (n = 15) as a primary (n = 27) or adjunctive postsurgical treatment (n = 49)., Main Outcome Measures: After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels below 2 ng/ml and normal IGF-I (acromegaly), normal 24-h urinary free cortisol, and cortisol less than 50 nmol/liter after low-dose dexamethasone test (CD) or two consecutive normal samplings of prolactin levels (prolactinoma)., Results: After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed for more than 120 months; rates of remission and hypopituitarism were similar to the whole cohort., Conclusions: SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas.

Growth-hormone hypersecretion, acromegaly, is associated with reduced life expectancy. First line treatment remains surgery, but remission rates vary between 50% and 90%. In case of lack of surgical remission or recurrence, somatostatin agonists can be proposed. However, about 30% of patients are partially or totally resistant to this treatment. The growth hormone receptor antagonist pegvisomant currently needs more prolonged follow-up studies. Conventional radiotherapy and radiosurgery are two radiation treatment modalities that can be proposed to these resistant patients. Reported rates of remission for conventional radiotherapy range between 50% and 60% in patients with acromegaly, with a time to remission delayed by several years, and adverse effects including high rates of hypopituitarism. This treatment could be proposed to patients with aggressive adenomas, in whom surgery cannot allow biochemical control. In contrast, studies on stereotactic radiosurgery reported lower rates of remission, with faster growth hormone hypersecretion decline, and a lower risk of adverse effects. However, this latter technique requires a well defined target volume, which limits its indications. The high precision of this technique makes it possible to be used as an alternative primary treatment to surgery. We reviewed major advantages and drawbacks of each of these techniques, based on recent studies to try to define their respective indications in the therapeutic algorithm of acromegaly.

There are two principal types of treatment for pituitary adenomas: fractionated conventional radiation therapy, based on biological selectivity, and radiosurgery, which is delivered in a single dose, based on anatomic selectivity and indicated preferentially for small tumors sufficiently distant from the optic chiasm. Conventional radiation therapy is effective against secretion in 60-80% of cases and radiosurgery in 40-50%, depending on the type of secretion. Maximum antisecretory efficacy is not reached immediately: this delay is longer for conventional radiation therapy (5-10 years) than for radiosurgery (2-3 years). In both cases, antisecretory treatment must be started, while awaiting remission. Radiation therapy and radiosurgery make it possible to stabilize or diminish tumor volume in 70-100% of cases. This is especially useful in the case of an active residue after surgery for non-secreting adenoma, but the long-term side effects of radiation must be borne in mind. The principal side effect is the onset of a pituitary deficiency (in more than 50% of cases after radiation therapy, 20% after radiosurgery). The risk increases with time since treatment. Other very long-term side effects have been described with radiation therapy: radiation-induced tumors, cerebral necrosis, strokes, etc. The role of radiosurgery and radiation therapy is growing ever more limited, because of the increasing efficacy of drug treatments and the excellent surgical results of experienced teams.

Objective: Though transsphenoidal surgery remains the first-line treatment of Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing's disease., Design: Forty patients with Cushing's disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment., Methods: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test., Results: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12-48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm(3), P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02)., Conclusion: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

Context: Because surgical and medical therapies of acromegaly all have specific limitations, radiotherapy has been used as an adjunctive strategy. Stereotactic radiosurgery has not yet been widely evaluated., Objective: The objective was to perform an analysis of long-term hormonal effects and tolerance of gamma knife radiosurgery., Design: Eighty-two patients were prospectively studied over a decade, with a mean follow-up of 49.5 months., Setting: All patients were treated at the Department of Functional Neurosurgery of Marseille, France., Patients: The patients included 82 with active acromegaly, of whom 63 had previous transsphenoidal surgery., Intervention: Intervention included radiosurgery using the Leksell Gamma Unit B model., Main Outcome Measures: Remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (at least 3 months)., Results: Seventeen percent of the patients were in remission without any treatment. Twenty-three percent previously uncontrolled on somatostatin agonists fulfilled the same criteria after gamma knife while maintained on medical treatment. Initial GH and IGF-I levels off somatostatin agonists were significantly higher in uncured than in remission group (P = 0.01 and 0.047, respectively). Withdrawal of somatostatin agonists at the time of radiosurgery had no incidence on the outcome. No significant difference was found in success rate whether patients had previously been treated or not. Long-term side effects included complete (n = 2) or partial (n = 12) hypopituitarism diagnosed 1-7 yr after gamma knife., Conclusions: Gamma knife radiosurgery may represent a therapeutic approach in patients with moderate initial or residual GH hypersecretion.