Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study

2013 ◽  
Vol 119 (2) ◽  
pp. 446-456 ◽  
Author(s):  
Jason P. Sheehan ◽  
Robert M. Starke ◽  
David Mathieu ◽  
Byron Young ◽  
Penny K. Sneed ◽  
...  

Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1–223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02–1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96–4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

2012 ◽  
Vol 116 (6) ◽  
pp. 1304-1310 ◽  
Author(s):  
Christopher P. Cifarelli ◽  
David J. Schlesinger ◽  
Jason P. Sheehan

Object Gamma Knife surgery (GKS) has become a significant component of neurosurgical treatment for recurrent secretory and nonsecretory pituitary adenomas. Although the long-term risks of visual dysfunction following microsurgical resection of pituitary adenomas has been well studied, the comparable risk following radiosurgery is not well defined. This study evaluates the long-term risks of ophthalmological dysfunction following GKS for recurrent pituitary adenomas. Methods An analysis of 217 patients with recurrent secretory (n = 131) and nonsecretory (n = 86) pituitary adenomas was performed to determine the incidence of and risk factors for subsequent development of visual dysfunction. Patients underwent ophthalmological evaluation as part of post-GKS follow-up to assess for new or worsened cranial nerve II, III, IV, or VI palsies. The median follow-up duration was 32 months. The median maximal dose was 50 Gy, and the median peripheral dose was 23 Gy. A univariate analysis was performed to assess for risk factors of visual dysfunction post-GKS. Results Nine patients (4%) developed new visual dysfunctions, and these occurred within 6 hours to 34 months following radiosurgery. None of these 9 patients had tumor growth on post-GKS neuroimaging studies. Three of these patients had permanent deficits whereas in 6 the deficits resolved. Five of the 9 patients had prior GKS or radiotherapy, which resulted in a significant increase in the incidence of cranial nerve dysfunction (p = 0.0008). An increased number of isocenters (7.1 vs 5.0, p = 0.048) was statistically related to the development of visual dysfunction. Maximal dose, margin dose, optic apparatus dose, tumor volume, cavernous sinus involvement, and suprasellar extension were not significantly related to visual dysfunction (p >0.05). Conclusions Neurological and ophthalmological assessment in addition to routine neuroimaging and endocrinological follow-up are important to perform following GKS. Patients with a history of radiosurgery or radiation therapy are at higher risk of cranial nerve deficits. Also, a reduction in the number of isocenters delivered, along with volume treated, particularly in the patients with secretory tumors, appears to be the most reasonable strategy to minimize the risk to the visual system when treating recurrent pituitary adenomas with stereotactic radiosurgery.


2014 ◽  
Vol 120 (6) ◽  
pp. 1268-1277 ◽  
Author(s):  
Jason P. Sheehan ◽  
Robert M. Starke ◽  
Hideyuki Kano ◽  
Anthony M. Kaufmann ◽  
David Mathieu ◽  
...  

Object Parasellar and sellar meningiomas are challenging tumors owing in part to their proximity to important neurovascular and endocrine structures. Complete resection can be associated with significant morbidity, and incomplete resections are common. In this study, the authors evaluated the outcomes of parasellar and sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an adjunct to microsurgical removal or conventional radiation therapy and as a primary treatment modality. Methods A multicenter study of patients with benign sellar and parasellar meningiomas was conducted through the North American Gamma Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors identified all patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were also required to have a minimum of 6 months of imaging and clinical follow-up after GKRS. Factors predictive of new neurological deficits following GKRS were assessed via univariate and multivariate analyses. Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. Results The authors identified 763 patients with sellar and/or parasellar meningiomas treated with GKRS. Patients were assessed clinically and with neuroimaging at routine intervals following GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of 56 years (range 8–90 years). Three hundred fifty-five patients (50.7%) had undergone at least one resection before GKRS, and 3.8% had undergone prior radiation therapy. The median follow-up after GKRS was 66.7 months (range 6–216 months). At the last follow-up, tumor volumes remained stable or decreased in 90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10 years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery, prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased the likelihood of tumor progression after GKRS. At the last clinical follow-up, 86.2% of patients demonstrated no change or improvement in their neurological condition, whereas 13.8% of patients experienced symptom progression. New or worsening cranial nerve deficits were seen in 9.6% of patients, with cranial nerve (CN) V being the most adversely affected nerve. Functional improvements in CNs, especially in CNs V and VI, were observed in 34% of patients with preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6% of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome with tumor growth and accompanying neurological decline was statistically more likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior surgery (p = 0.021). Conclusions Gamma Knife radiosurgery provides a high rate of tumor control for patients with parasellar or sellar meningiomas, and tumor control is accompanied by neurological preservation or improvement in most patients.


2012 ◽  
Vol 116 (3) ◽  
pp. 598-604 ◽  
Author(s):  
Brian D. Milligan ◽  
Bruce E. Pollock ◽  
Robert L. Foote ◽  
Michael J. Link

Object Gamma Knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors. Methods Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm3 (range 5.3–19.1 cm3). The median maximum posterior fossa diameter was 2.8 cm (range 2.5–3.8 cm). The median tumor margin dose was 12 Gy (range 12–14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26–121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection. Results Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction. Conclusions Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.


Neurosurgery ◽  
2011 ◽  
Vol 69 (6) ◽  
pp. 1188-1199 ◽  
Author(s):  
Kyung-Jae Park ◽  
Hideyuki Kano ◽  
Phillip V. Parry ◽  
Ajay Niranjan ◽  
John C. Flickinger ◽  
...  

Abstract BACKGROUND Nonfunctional pituitary adenomas (NFPAs) represent approximately 50% of all pituitary tumors. OBJECTIVE To evaluate the long-term outcomes of stereotactic radiosurgery for NFPAs. METHODS We evaluated the management outcomes of Gamma Knife radiosurgery in 125 patients with NFPAs over an interval of 22 years. The median patient age was 54 years (range, 16-88 years). One hundred ten patients (88%) had residual or recurrent tumors after ≥ 1 surgical procedures, and 17 (14%) had undergone prior fractionated radiation therapy. The median target volume was 3.5 cm3 (range, 0.4-28.1 cm3), and the median tumor margin dose was 13.0 Gy (range, 10-25 Gy). RESULTS Tumor volume decreased in 66 patients (53%), remained stable in 46 (37%), and increased in 13 (10.4%) during a median of 62 months (maximum, 19 years) of imaging follow-up. The actuarial tumor control rates at 1, 5, and 10 years were 99%, 94%, and 76%, respectively. Factors associated with a reduced progression-free survival included larger tumor volume (≥ 4.5 cm3) and ≥ 2 prior recurrences. Of 88 patients with residual pituitary function, 21 (24%) suffered new hormonal deficits at a median of 24 months (range, 3-114 months). Prior radiation therapy increased the risk of developing new pituitary hormonal deficits. One patient (0.8%) had a decline in visual function, and 2 (1.6%) developed new cranial neuropathies without tumor progression. CONCLUSION Stereotactic radiosurgery can provide effective management for patients with newly diagnosed NFPAs and for those after prior resection and/or radiation therapy.


2006 ◽  
Vol 105 (Supplement) ◽  
pp. 26-30 ◽  
Author(s):  
Mooseong Kim ◽  
Sunghwa Paeng ◽  
Seyoung Pyo ◽  
Yeonggyun Jeong ◽  
Sunil Lee ◽  
...  

ObjectPituitary adenomas have been treated using a variety of modalities including resection, medication, fractionated radiotherapy, and stereotactic radiosurgery. The policy has been that all adenomas should first be treated with resection to reduce the volume of the tumor. The authors' study was conducted to determine the efficacy of using Gamma Knife surgery (GKS) for pituitary adenomas invading the cavernous sinus.MethodsOf 397 patients with pituitary tumors who underwent GKS between October 1994 and October 2005, 68 patients had pituitary macroadenomas invading the cavernous sinus. Sixty-seven cases were available for follow up. The mean age of the patients in these cases was 42.8 years (range 14–73 years). The male/female ratio was 0.8:1. The mean adenoma volume was 9.3 cm3. A total of 24 patients had undergone craniotomies and resection, and 11 patients had undergone transsphenoidal surgery prior to GKS. The mean follow-up period was 32.8 months. Tumor control was defined as a decrease or no change in tumor volume after GKS. Endocrinological improvement was defined as a decline in hormone levels to below 50% of the pre-GKS level.Tumor control was achieved in 95.5% of the cases. Endocrinological improvement was achieved in 68% of 25 patients. One patient suffered hypopituitarism after GKS.Conclusions Gamma Knife surgery is a safe and effective treatment for invasive pituitary macroadenoma with few complications.


2007 ◽  
Vol 106 (6) ◽  
pp. 980-987 ◽  
Author(s):  
Jay Jagannathan ◽  
Jason P. Sheehan ◽  
Nader Pouratian ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  

Object In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas. Methods A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy). Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes. Conclusions Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yanli Li ◽  
Lisha Wu ◽  
Tingting Quan ◽  
Junyi Fu ◽  
Linhui Cao ◽  
...  

ObjectiveThis study aimed to report the characteristic of tumor regrowth after gamma knife radiosurgery (GKRS) and outcomes of repeat GKRS in nonfunctioning pituitary adenomas (NFPAs).Design and MethodsThis retrospective study consisted of 369 NFPA patients treated with GKRS. The median age was 45.2 (range, 7.2–84.0) years. The median tumor volume was 3.5 (range, 0.1–44.3) cm3.ResultsTwenty-four patients (6.5%) were confirmed as regrowth after GKRS. The regrowth-free survivals were 100%, 98%, 97%, 86% and 77% at 1, 3, 5, 10 and 15 year, respectively. In multivariate analysis, parasellar invasion and margin dose (&lt;12 Gy) were associated with tumor regrowth (hazard ratio [HR] = 3.125, 95% confidence interval [CI] = 1.318–7.410, p = 0.010 and HR = 3.359, 95% CI = 1.347–8.379, p = 0.009, respectively). The median time of regrowth was 86.1 (range, 23.2–236.0) months. Previous surgery was associated with tumor regrowth out of field (p = 0.033). Twelve patients underwent repeat GKRS, including regrowth in (n = 8) and out of field (n = 4). Tumor shrunk in seven patients (58.3%), remained stable in one (8.3%) and regrowth in four (33.3%) with a median repeat GKRS margin dose of 12 (range, 10.0–14.0) Gy. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.ConclusionsParasellar invasion and tumor margin dose (&lt;12 Gy) were independent risk factors for tumor regrowth after GKRS. Repeat GKRS might be effective on tumor control for selected patients. For regrowth in field due to relatively insufficient radiation dose, repeat GKRS might offer satisfactory tumor control. For regrowth out of field, preventing regrowth out of field was the key management. Sufficient target coverage and close follow-up might be helpful.


2007 ◽  
Vol 106 (6) ◽  
pp. 988-993 ◽  
Author(s):  
William J. Mauermann ◽  
Jason P. Sheehan ◽  
Daniel R. Chernavvsky ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  

Object Patients with adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). Methods The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. Conclusions Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.


2018 ◽  
Vol 79 (06) ◽  
pp. 580-585
Author(s):  
Rawee Ruangkanchanasetr ◽  
John Lee ◽  
Suneel Nagda ◽  
Geoffrey Geiger ◽  
James Kolker ◽  
...  

Objective Gamma Knife stereotactic radiosurgery (GK-SRS) is a preferred treatment option for tumors of the jugular foramen. We hypothesized that GK-SRS toxicity is higher for lower cranial nerve schwannomas than for glomus jugulare tumors despite anatomically similar locations. Methods We performed a retrospective review of all patients who received GK-SRS for glomus jugulare tumors and lower cranial nerve schwannomas at our institution between 2006 and 2014. Because of small sample sizes, Fisher's exact tests and logistic regression techniques were employed using SPSS. Result We identified 20 glomus jugulare tumors and 6 lower cranial nerve schwannoma patients with a median follow-up of 17 months. Median marginal dose was 16 Gy (range 13–18 Gy) and 12.5 Gy (range 12–14 Gy), respectively. All except one patient had tumor control at last follow-up visit. No worsening of pre-existing neurological deficits was observed. There were seven patients who developed any new neurological deficit after GK-SRS, four from the glomus group, and three from the schwannoma group (20 and 50% of each group, respectively). Only two of seven patients had permanent new neurological deficits. Both of them were in the schwannoma group. Univariate analysis showed that only a diagnosis of schwannoma had a greater risk of permanent new cranial nerve complication after GK-SRS compared with diagnosis of glomus jugulare (p = 0.046). Conclusion Although the marginal dose for glomus jugulare is greater, our study suggests that the risk of a new permanent neurological deficit after GK-SRS was higher in the schwannoma group compared with the glomus group.


Neurosurgery ◽  
2003 ◽  
Vol 53 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Zbigniew Petrovich ◽  
Cheng Yu ◽  
Steven L. Giannotta ◽  
Chi-Shing Zee ◽  
Michael L.J. Apuzzo

Abstract OBJECTIVE In recent years, gamma knife radiosurgery (GKRS) has emerged as an important treatment modality in the management of pituitary adenomas. Treatment results after performing GKRS and the complications of this procedure are reviewed. METHODS Between 1994 and 2002, a total of 78 patients with pituitary adenomas underwent a total of 84 GKRS procedures in our medical center. This patient group comprised 46 men (59%) and 32 women (41%). All patients were treated for recurrent or residual disease after surgery or radiotherapy, with 83% presenting with extensive tumor involvement. The cavernous sinus was involved in 75 patients (96%), and 22 patients (28%) had hormone-secreting adenomas. This latter subset of patients included 12 prolactinomas (15%), 6 growth-hormone secreting tumors (8%), and 4 adrenocorticotropic hormone-secreting tumors (5%). The median tumor volume was 2.3 cm3, and the median radiation dose was 15 Gy defined to the 50% isodose line. The mean and median follow-up periods were 41 and 36 months, respectively. RESULTS GKRS was tolerated well in these patients; acute toxicity was uncommon and of no clinical significance. Late toxicity was noted in three patients (4%) and consisted of VIth cranial nerve palsy. In two patients, there was spontaneous resolution of this palsy, and in one patient, it persisted for the entire 3-year duration of follow-up. Of the 15 patients who presented with cranial nerve dysfunction, 8 (53%) experienced complete recovery and 3 (20%) showed major improvement within 12 months of therapy. Tumor volume reduction was slow, with 30% of patients showing decreased tumor volume more than 3 years after undergoing GKRS. None of the 56 patients with nonfunctioning tumors showed progression in the treated volume, and 4 (18%) of the 22 hormone-secreting tumors relapsed (P = 0.008). Of the four patients with adrenocorticotropic hormone-secreting adenomas, therapy failed in two of them. All six patients with growth hormone-producing tumors responded well to therapy. Of the 12 patients with prolactinomas 10 (83%) had normalization of hormone level and 2 patients experienced increasing prolactin level. Two patients with prolactinomas had three normal pregnancies after undergoing GKRS. CONCLUSION GKRS is a safe and effective therapy in selected patients with pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus. A radiation dose higher than 15 Gy is probably needed to improve control of hormone-secreting adenomas. Longer follow-up is required for a more complete assessment of late toxicity and treatment efficacy.


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