Gamma Knife surgery for Cushing's disease

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.

Download Full-text

Gamma Knife surgery for invasive pituitary macroadenoma

Journal of Neurosurgery ◽

10.3171/sup.2006.105.7.26 ◽

2006 ◽

Vol 105 (Supplement) ◽

pp. 26-30 ◽

Cited By ~ 10

Author(s):

Mooseong Kim ◽

Sunghwa Paeng ◽

Seyoung Pyo ◽

Yeonggyun Jeong ◽

Sunil Lee ◽

...

Keyword(s):

Gamma Knife ◽

Cavernous Sinus ◽

Pituitary Adenomas ◽

Gamma Knife Surgery ◽

Tumor Control ◽

Pituitary Macroadenoma ◽

Female Ratio ◽

Fractionated Radiotherapy ◽

The Mean

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.

Download Full-text

Gamma knife surgery for cavernous hemangiomas: an analysis of 125 patients

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0081 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 81-86 ◽

Cited By ~ 16

Author(s):

Kang-Du Liu ◽

Wen-Yuh Chung ◽

Hsiu-Mei Wu ◽

Cheng-Ying Shiau ◽

Ling-Wei Wang ◽

...

Keyword(s):

Gamma Knife ◽

Gamma Knife Surgery ◽

Content Type ◽

Cavernous Hemangiomas ◽

Rebleeding Rate ◽

Radiation Induced ◽

Bleeding Episodes ◽

The Mean ◽

Fine Print

Object. The authors sought to determine the value of gamma knife surgery (GKS) in the treatment of cavernous hemangiomas (CHs). Methods. Between 1993 and 2002, a total of 125 patients with symptomatic CHs were treated with GKS. Ninety-seven patients presented with bleeding and 45 of these had at least two bleeding episodes. Thirteen patients presented with seizures combined with hemorrhage, and 15 patients presented with seizures alone. The mean margin dose of radiation was 12.1 Gy and the mean follow-up time was 5.4 years. In the 112 patients who had bled the number of rebleeds after GKS was 32. These rebleeds were defined both clinically and based on magnetic resonance imaging for an annual rebleeding rate of 32 episodes/492 patient-years or 6.5%. Twenty-three of the 32 rebleeding episodes occurred within 2 years after GKS. Nine episodes occurred after 2 years; thus, the annual rebleeding rate after GKS was 10.3% for the first 2 years and 3.3% thereafter (p = 0.0038). In the 45 patients with at least two bleeding episodes before GKS, the rebleeding rate dropped from 29.2% (55 episodes/188 patient-years) before treatment to 5% (10 episodes/197 patient-years) after treatment (p < 0.0001). Among the 28 patients who presented with seizures, 15 (53%) had good outcomes (Engel Grades I and II). In this study of 125 patients, symptomatic radiation-induced complications developed in only three patients. Conclusions. Gamma knife surgery can effectively reduce the rebleeding rate after the first symptomatic hemorrhage in patients with CH. In addition, GKS may be useful in reducing the severity of seizures in patients with CH.

Download Full-text

Results of Gamma Knife surgery for Cushing's disease

Journal of Neurosurgery ◽

10.3171/2013.7.jns13217 ◽

2013 ◽

Vol 119 (6) ◽

pp. 1486-1492 ◽

Cited By ~ 55

Author(s):

Jason P. Sheehan ◽

Zhiyuan Xu ◽

David J. Salvetti ◽

Paul J. Schmitt ◽

Mary Lee Vance

Keyword(s):

Median Time ◽

Gamma Knife ◽

Cushing’S Disease ◽

Cranial Nerves ◽

Gamma Knife Surgery ◽

High Rate ◽

Cushing's Disease ◽

Tumor Control

Object Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease. Methods A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors. Results Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12–209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1–165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p < 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III. Conclusions Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.

Download Full-text

Gamma knife surgery for cavernous hemangiomas: an analysis of 125 patients

Journal of Neurosurgery ◽

10.3171/jns.2005.102.s_supplement.0081 ◽

2005 ◽

Vol 102 ◽

pp. 81-86 ◽

Cited By ~ 38

Author(s):

Kang-Du Liu ◽

Wen-Yuh Chung ◽

Hsiu-Mei Wu ◽

Cheng-Ying Shiau ◽

Ling-Wei Wang ◽

...

Keyword(s):

Gamma Knife ◽

Gamma Knife Surgery ◽

Content Type ◽

Cavernous Hemangiomas ◽

Rebleeding Rate ◽

Radiation Induced ◽

Bleeding Episodes ◽

The Mean ◽

Fine Print

Download Full-text

Brainstem cavernous malformations: the role of Gamma Knife surgery

Journal of Neurosurgery ◽

10.3171/2012.8.gks121066 ◽

2012 ◽

Vol 117 (Special_Suppl) ◽

pp. 164-169 ◽

Cited By ~ 13

Author(s):

Cheng-Chia Lee ◽

David Hung-Chi Pan ◽

Wen-Yuh Chung ◽

Kang-Du Liu ◽

Huai-Che Yang ◽

...

Keyword(s):

Gamma Knife ◽

Good Alternative ◽

Gamma Knife Surgery ◽

Neurological Deficits ◽

Cavernous Malformations ◽

Perifocal Edema ◽

Consciousness Disturbance ◽

Radiation Induced ◽

The Mean

Object The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention. Methods Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance. Results The mean size of the CMs at the time of GKS was 3.2 cm3 (range 0.1–14.6 cm3). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0–150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group. Conclusions Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

Download Full-text

Gamma Knife surgery for adrenocorticotropic hormone–producing pituitary adenomas after bilateral adrenalectomy

Journal of Neurosurgery ◽

10.3171/jns.2007.106.6.988 ◽

2007 ◽

Vol 106 (6) ◽

pp. 988-993 ◽

Cited By ~ 43

Author(s):

William J. Mauermann ◽

Jason P. Sheehan ◽

Daniel R. Chernavvsky ◽

Edward R. Laws ◽

Ladislau Steiner ◽

...

Keyword(s):

Pituitary Adenoma ◽

Gamma Knife ◽

Pituitary Adenomas ◽

Cranial Nerve ◽

Adrenocorticotropic Hormone ◽

Gamma Knife Surgery ◽

Nelson’S Syndrome ◽

Nelson's Syndrome ◽

Follow Up Studies

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.

Download Full-text

Stereotactic radiosurgery in patients with glomus jugulare tumors

Neurosurgical FOCUS ◽

10.3171/foc.2004.17.2.10 ◽

2004 ◽

Vol 17 (2) ◽

pp. 63-67 ◽

Cited By ~ 64

Author(s):

Bruce E. Pollock

Keyword(s):

Hearing Loss ◽

Vocal Cord ◽

Gamma Knife ◽

Cranial Nerve ◽

Vocal Cord Paralysis ◽

Gamma Knife Surgery ◽

Glomus Jugulare ◽

The Mean ◽

Primary Management

Object Microsurgical removal of glomus jugulare tumors is frequently associated with injury of the lower cranial nerves. To decrease the morbidity associated with tumor management in these patients, gamma knife surgery (GKS) was performed as an alternative to resection. Methods Between 1990 and 2003, 42 patients underwent GKS as the primary management (19 patients) or for recurrent glomus jugulare tumors (23 patients). Facial weakness and deafness were more common in patients with recurrent tumors than in those in whom primary GKS was performed (48% compared with 11%, p = 0.02). The mean tumor volume was 13.2 cm3; the mean tumor margin dose was 14.9 Gy. The mean follow-up period for the 39 patients in whom evaluation was possible was 44 months (range 6–149 months). After GKS, 12 tumors (31%) decreased in size, 26 (67%) were unchanged, and one (2%) grew. The patient whose tumor grew underwent repeated GKS. Progression-free survival after GKS was 100% at 3 and 7 years, and 75% at 10 years. Six patients (15%) experienced new deficits (hearing loss alone in three, facial numbness and hearing loss in one, vocal cord paralysis and hearing loss in one, and temporary imbalance and/or vertigo in one). In 26 patients in whom hearing could be tested before GKS, hearing preservation was achieved in 86 and 81% at 1 and 4 years posttreatment, respectively. No patient suffered a new lower cranial nerve deficit after one GKS session; the patient in whom repeated GKS was performed experienced a new vocal cord paralysis 1 year after his second procedure. Conclusions Gamma knife surgery provided tumor control with a low risk of new cranial nerve injury in early follow-up review. This procedure can be safely used as a primary management tool in patients with glomus jugulare tumors that do not have significant cervical extension, or in patients with recurrent tumors in this location.

Download Full-text

Gamma Knife surgery for parasellar meningiomas: long-term results including complications, predictive factors, and progression-free survival

Journal of Neurosurgery ◽

10.3171/2011.1.jns091939 ◽

2011 ◽

Vol 114 (6) ◽

pp. 1571-1577 ◽

Cited By ~ 44

Author(s):

Brian J. Williams ◽

Chun Po Yen ◽

Robert M. Starke ◽

Bhuvaneswara Basina ◽

James Nguyen ◽

...

Keyword(s):

Gamma Knife ◽

Cranial Nerve ◽

Tumor Volume ◽

Progression Free Survival ◽

Gamma Knife Surgery ◽

Tumor Control ◽

Free Survival ◽

Factors Associated ◽

The Mean

Object Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas. Methods The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19–85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2–54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed. Results The mean follow-up duration was 84 months (median 75.5 months, range 24–216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up. Conclusions Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.

Download Full-text

Gamma Knife surgery for trigeminal schwannoma

Journal of Neurosurgery ◽

10.3171/jns.2007.106.5.839 ◽

2007 ◽

Vol 106 (5) ◽

pp. 839-845 ◽

Cited By ~ 44

Author(s):

Jason Sheehan ◽

Chun Po Yen ◽

Yasser Arkha ◽

David Schlesinger ◽

Ladislau Steiner

Keyword(s):

Gamma Knife ◽

Gamma Knife Surgery ◽

Long Term Results ◽

University Of Virginia ◽

Trigeminal Schwannoma ◽

The Mean ◽

The University ◽

Lost To Follow Up

Object Trigeminal schwannomas are rare intracranial tumors. In the past, resection and radiation therapy were the mainstays of their treatment. More recently, neurosurgeons have begun to use radiosurgery in the treatment of trigeminal schwannomas because of its successful use in the treatment of vestibular schwannomas. In this article the authors evaluate the radiological and clinical outcomes in a series of patients in whom Gamma Knife surgery (GKS) was used to treat trigeminal schwannomas. Methods Twenty-six patients with trigeminal schwannomas underwent GKS at the University of Virginia Lars Lek-sell Gamma Knife Center between 1989 and 2005. Five of these patients had neurofibromatosis and one patient was lost to follow up. The median tumor volume was 3.96 cm3, and the mean follow-up period was 48.5 months. The median prescription radiation dose was 15 Gy, and the median prescription isodose configuration was 50%. There was clinical improvement in 18 patients (72%), a stable lesion in four patients (16%), and worsening of the disease in three patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained stable in 10 patients (40%), and increased in size in three patients (12%). These results were comparable for primary and adjuvant GKSs. No tumor growth following GKS was observed in the patients with neurofibromatosis. Conclusions Gamma Knife surgery affords a favorable risk-to-benefit profile for patients harboring trigeminal schwannomas. Larger studies with open-ended follow-up review will be necessary to determine the long-term results and complications of GKS in the treatment of trigeminal schwannomas.

Download Full-text

Long-term results of gamma knife surgery for growth hormone—producing pituitary adenoma: is the disease difficult to cure?

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0119 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 119-123 ◽

Cited By ~ 5

Author(s):

Tatsuya Kobayashi ◽

Yoshimasa Mori ◽

Yukio Uchiyama ◽

Yoshihisa Kida ◽

Shigeru Fujitani

Keyword(s):

Growth Hormone ◽

Gamma Knife ◽

Pituitary Adenomas ◽

Gamma Knife Surgery ◽

Long Term Results ◽

Content Type ◽

The Mean ◽

Dose Radiation ◽

Fine Print

Object. The authors conducted a study to determine the long-term results of gamma knife surgery for residual or recurrent growth hormine (GH)—producing pituitary adenomas and to compare the results with those after treatment of other pituitary adenomas. Methods. The series consisted of 67 patients. The mean tumor diameter was 19.2 mm and volume was 5.4 cm3. The mean maximum dose was 35.3 Gy and the mean margin dose was 18.9 Gy. The mean follow-up duration was 63.3 months (range 13–142 months). The tumor resolution rate was 2%, the response rate 68.3%, and the control rate 100%. Growth hormone normalization (GH < 1.0 ng/ml) was found in 4.8%, nearly normal (< 2.0 ng/ml) in 11.9%, significantly decreased (< 5.0 ng/ml) in 23.8%, decreased in 21.4%, unchanged in 21.4%, and increased in 16.7%. Serum insulin-like growth factor (IGF)—1 was significantly decreased (IGF-1 < 400 ng/ml) in 40.7%, decreased in 29.6%, unchanged in 18.5%, and increased in 11.1%, which was almost parallel to the GH changes. Conclusions. Gamma knife surgery was effective and safe for the control of tumors; however, normalization of GH and IGF-1 secretion was difficult to achieve in cases with large tumors and low-dose radiation. Gamma knife radiosurgery is thus indicated for small tumors after surgery or medication therapy when a relatively high-dose radiation is required.

Download Full-text