BACKGROUND: A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS: We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS: Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION: These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING: None.

• MeSH
• dospělí MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorová transformace buněk účinky záření   MeSH
• nádory mozku epidemiologie   etiologie   patologie   MeSH
• nádory vyvolané zářením epidemiologie   etiologie   patologie   MeSH
• následné studie MeSH
• radiochirurgie škodlivé účinky   MeSH
• retrospektivní studie MeSH
• riziko MeSH
• sekundární malignity epidemiologie   etiologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVE: Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing's disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas. METHODS: An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12-40.0 Gy) at a median isodose of 50%. RESULTS: The median endocrine follow-up was 69.5 months (range 9-246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2. CONCLUSIONS: Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.

• MeSH
• akromegalie diagnostické zobrazování   chirurgie   MeSH
• Cushingův syndrom diagnostické zobrazování   chirurgie   MeSH
• dospělí MeSH
• internacionalita * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• radiochirurgie metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Stereotactic radiosurgery (SRS) is used to manage patients with Cushing disease (CD) who have failed surgical/medical management. Because many patients with recurrent/persistent CD lack an identifiable adenoma on neuroimaging, whole-sellar SRS has been increasingly used. Thus, we sought to define the outcomes of patients undergoing whole-sellar SRS. METHODS: An international, multicenter, retrospective cohort design was used to define clinical/endocrine outcomes for patients undergoing whole-sellar SRS for CD. Propensity-score matching was used to compare patients undergoing whole-sellar SRS and patients who underwent discreet adenoma-targeted SRS. RESULTS: A total of 68 patients underwent whole-sellar SRS, with a mean endocrine follow-up of 5.3 years. The mean treatment volume was 2.6 cm3, and the mean margin dose was 22.4 Gy. The 5-year actuarial remission rate was 75.9%, and the median time to remission was 12-months. Treatment volumes >1.6 cm3 were associated with shorter times to remission (P < 0.05). The 5-year recurrence-free survival rate was 86.0%. Decreased margin and maximum treatment doses were associated with recurrence (P < 0.05). New pituitary hormone deficiency occurred in 15 patients (22.7%). An additional 210 patients were identified who underwent adenoma-targeted SRS. There was no difference in remission rate, time to remission, recurrence-free survival or new endocrinopathy development between patients who underwent whole-sellar SRS and those who underwent discreet adenoma-targeted SRS. CONCLUSIONS: Whole-sellar GKRS is effective in controlling CD when an adenoma is not clearly defined on imaging or when an invasive adenoma is suspected at the time of initial surgery. Patients who undergo whole-sellar SRS have outcomes and rates of new pituitary hormone deficiency similar to those of patients who undergo discrete adenoma-targeted GKRS.

• MeSH
• adrenokortikotropní hormon metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• hydrokortison metabolismus   MeSH
• hypersekrece ACTH v hypofýze chirurgie   MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• radiochirurgie metody   MeSH
• sella turcica chirurgie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Context: Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. Objective: To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. Design: International, multicenter, retrospective cohort analysis. Setting: Ten medical centers participating in the International Gamma Knife Research Foundation. Patients: Patients with CD with >6 months endocrine follow-up. Intervention: SRS using Gamma Knife radiosurgery. Main Outcome Measures: The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. Results: In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. Conclusions: SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.

• MeSH
• adenom hypofýzy vylučující ACTH sekrece   chirurgie   MeSH
• adenom sekrece   chirurgie   MeSH
• dítě MeSH
• dospělí MeSH
• hypersekrece ACTH v hypofýze chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• radiochirurgie * metody   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH