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Gamma Knife surgery for Cushing's disease

Jay Jagannathan, Jason P. Sheehan, Nader Pouratian, Edward R. Laws, Ladislau Steiner, and Mary Lee Vance


In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas.


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.


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.

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Radiosurgery of growth hormone–producing pituitary adenomas: factors associated with biochemical remission

Bruce E. Pollock, Jeffrey T. Jacob, Paul D. Brown, and Todd B. Nippoldt


The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission.


Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)–producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor–I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22–168 months).

Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6–63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2–6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4–13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years.


Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH–producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.

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A simple dose gradient measurement tool to complement the conformity index

Ian Paddick and Bodo Lippitz

✓A dose gradient index (GI) is proposed that can be used to compare treatment plans of equal conformity. The steep dose gradient outside the radiosurgical target is one of the factors that makes radiosurgery possible. It therefore makes sense to measure this variable and to use it to compare rival plans, explore optimal prescription isodoses, or compare treatment modalities.

The GI is defined as the ratio of the volume of half the prescription isodose to the volume of the prescription isodose. For a plan normalized to the 50% isodose line, it is the ratio of the 25% isodose volume to that of the 50% isodose volume.

The GI will differentiate between plans of similar conformity, but with different dose gradients, for example, where isocenters have been inappropriately centered on the edge of the target volume.

In a retrospective series of 50 dose plans for the treatment of vestibular schwannoma, the optimal prescription isodose was assessed. A mean value of 40% (median 38%, range 30–61%) was calculated, not 50% as might be anticipated. The GI can show which of these prescription isodoses will give the steepest dose falloff outside the target.

When planning a multiisocenter treatment, there may be a temptation to place some isocenters on the edge of the target. This has the apparent advantage of producing a plan of good conformity and a predictable prescription isodose; however, it risks creating a plan that has a low dose gradient outside the target. The quality of this dose gradient is quantified by the GI.

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Gamma knife surgery for dural arteriovenous shunts: 25 years of experience

Michael Söderman, Göran Edner, Kaj Ericson, Bengt Karlsson, Tiit Rähn, Elfar Ulfarsson, and Tommy Andersson


The aim of this study was to assess the clinical efficacy of gamma knife surgery (GKS) in the treatment of dural arteriovenous shunts (DAVSs).


From a database of more than 1600 patients with intracranial arteriovenous shunts that had been treated with GKS, the authors retrospectively and prospectively identified 53 patients with 58 DAVSs from the period between 1978 and 2003. Four patients were lost to follow-up evaluation and were excluded from the series. Thus, this study is based on the remaining 49 patients with 52 DAVSs. Thirty-six of the shunts drained into the cortical venous system, either directly or indirectly, and 22 of these were associated with intracranial hemorrhage on patient presentation. The mean prescription radiation dose was 22 Gy (range 10–28 Gy).

All patients underwent a clinical follow-up examination. In 41 cases of DAVS a follow-up angiography study was performed. At the 2-year follow-up visit, 28 cases (68%) had angiographically proven obliteration of the shunt and in another 10 cases (24%) there was significant flow regression. Three shunts remained unchanged.

There was one immediate minor complication related to the administration of radiation. Furthermore, one patient had a radiation-induced complication 10 years after treatment, although she recovered completely. There was one posterior fossa bleed 2 months after radiosurgery; a hematoma, as well as a lesion, was evacuated, and the patient recovered uneventfully. A second patient had an asymptomatic occipital hemorrhage approximately 6 months postradiosurgery.

The clinical outcome after GKS was significantly better than that in patients with naturally progressing shunts (p < 0.01, chi-square test); figures on the latter have been reported previously.


Gamma knife surgery is an effective treatment for DAVSs, with a low risk of complications. Major disadvantages of this therapy include the time elapsed before obliteration and the possibility that not all shunts will be obliterated. Cortical venous drainage from a DAVS, a risk factor for intracranial hemorrhage, is therefore a relative contraindication. Consequently, GKS can be used in the treatment of both benign DAVSs with subjectively intolerable bruit and aggressive DAVSs not responsive to endovascular treatment or surgery.

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Gamma surgery in the treatment of nonsecretory pituitary macroadenoma

Vincenzo Mingione, Chun Po Yen, Mary Lee Vance, Melita Steiner, Jason Sheehan, Edward R. Laws, and Ladislau Steiner


The authors report on a retrospective analysis of the imaging and clinical outcomes following gamma surgery in 100 patients with nonsecretory pituitary macroadenoma.


Between June 1989 and March 2004, 100 consecutive patients with nonsecretory pituitary macroadenoma were treated at the Lars Leksell Center for Gamma Surgery, University of Virginia Health System (Charlottesville, VA). Ninety-two patients had residual or recurrent macroadenoma following one or more surgical procedures. In eight patients, gamma surgery was the primary treatment. Ten patients received conventional fractionated radiotherapy before the gamma surgery. Sixty-nine patients required hormone replacement therapy for one or more deficits before gamma knife treatment. Peripheral doses between 5 and 25 Gy (mean 18.5 Gy) were administered.

Imaging and endocrinological follow-up evaluations were performed in 90 patients; these studies ranged from 6 to 142 months (mean 44.9 months) and 6 to 127 months (mean 47.9 months), respectively. Tumor volume decreased in 59 patients (65.6%), remained unchanged in 24 (26.7%), and increased in seven (7.8%). The minimal effective peripheral dose was 12 Gy; peripheral doses greater than 20 Gy did not seem to provide additional benefit. Of 61 patients with a partially or fully functioning pituitary gland and follow-up data, 12 (19.7%) suffered new hormone deficits following gamma surgery. In patients with endocrinological follow-up data that had been collected over more than 2 years, the rate of new deficits was 25%. No neurological morbidity or death was related to treatment.


Current experience suggests that gamma surgery is an appropriate means of managing recurrent or residual nonsecretory pituitary macroadenoma following microsurgery and a primary treatment in selected patients. To evaluate definite rates of recurrence and new endocrine deficiencies, long-term follow-up studies are needed.

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Prospective controlled trial of gamma knife surgery for essential trigeminal neuralgia

Jean Régis, Philippe Metellus, Motohiro Hayashi, Philippe Roussel, Anne Donnet, and Françoise Bille-Turc


Stereotactic radiosurgery is an alternative to conventional surgery for the treatment of trigeminal neuralgia. The authors conducted a prospective evaluation of the safety and efficacy of this method in a large series of patients.


A total of 100 patients presenting with trigeminal neuralgia were treated and followed up for a minimum of 12 months. The mean age was 68.2 years; 54 patients were male, and 46 were female. Seven had a history of multiple sclerosis, and 42 had already received conventional surgical treatment for trigeminal neuralgia. The intervention consisted of gamma knife surgery to the retrogasserian cisternal portion of the fifth cranial nerve. The median dose used at the maximum was 85 Gy (range 70–90 Gy). The number and intensity of pain attacks were recorded by the patient from 3 months before radiosurgery to a minimum of 12 months after treatment. Before and a minimum of 12 months after treatment, the patient completed a quality-of-life questionnaire. Neurological examination and quantitative sensory testing to evaluate sensory perception were performed by an independent neurologist over this same time period.

At the last visit 83 of 100 patients were reported to be pain free. Fifty-eight of these 83 patients had stopped taking medication during the study. All quality-of-life parameters were improved (p < 0.001). Six patients reported facial paresthesia, and four patients reported hypesthesia. These symptoms were classified as mild. None of the complications reported for other techniques were observed.


Radiosurgery is a safe and effective alternative treatment for trigeminal neuralgia and is associated with a particularly low rate of hypesthesia.

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Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error

Technical note

John W. Snell, Jason Sheehan, Matei Stroila, and Ladislau Steiner

✓ The Gamma Knife has played an increasingly important role in the neurosurgical treatment of patients. Intracranial lesions are not removed by radiosurgery. Rather, the goal of treatment is to induce tumor control. During planning, the creation of dose–volume histograms requires an accurate volumetric analysis of intracranial lesions selected for radiosurgery. In addition, an accurate follow-up imaging analysis of tumor volume is essential for assessing the results of radiosurgery. Nevertheless, sources of volumetric error and their expected magnitudes must be properly understood so that the operator may correctly interpret apparent changes in tumor volume. In this paper, the authors examine the often-neglected contributions of imaging geometry (principally image slice thickness and separation) to overall volumetric error.

One of the fundamental sources of volumetric error is that resulting from the geometry of the acquisition protocol. The authors consider the image sampling geometry of tomographic modalities and its contribution to volumetric error through a simulation framework in which a synthetic digital tumor is taken as the primary model. Because the exact volume of the digital phantom can be computed, the volume estimates derived from tomographic “slicing” can be directly compared precisely and independently from other error sources. In addition to providing empirical bounds on volumetric error, this approach provides a tool for guiding the specification of imaging protocols when a specific volumetric accuracy, or volume change sensitivity, for particular structures is sought a priori.

Using computational geometry techniques, the volumetric error associated with image acquisition geometry was shown to be dependent on the number of slices through the region of interest (ROI) and the lesion volume. With a minimum of five slices through the ROI, the volume of a compact lesion could be calculated accurately with less than 10% error, which was the predetermined goal for the purposes of computing accurate dose–volume histograms and determining follow-up changes in tumor volume.

Accurate dose–volume histograms can be generated and follow-up volumetric assessments performed, assuming accurate lesion delineation, when the object is visualized on at least five axial slices. Volumetric analysis based on fewer than five slices yields unacceptably larger errors (that is, > 10%). These volumetric findings are particularly relevant for radiosurgical treatment planning and follow-up analysis. Through the application of this volumetric methodology and a greater understanding of the error associated with it, neurosurgeons can better perform radiosurgery and assess its outcome.

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Long-term results of gamma knife surgery for the treatment of craniopharyngioma in 98 consecutive cases

Tatsuya Kobayashi, Yoshihisa Kida, Yoshimasa Mori, and Toshinori Hasegawa


The authors analyzed the long-term outcomes of gamma knife surgery (GKS) for residual or recurrent craniopharyngiomas after microsurgery and the effects of dose reduction.


A total of 107 patients with craniopharyngiomas were treated with GKS at Komaki City Hospital during the past 12 years, and 98 patients were followed up for 6 to 148 months (mean 65.5 months). The mean tumor diameter and volume were 18.8 mm and 3.5 ml, respectively. These tumors were treated with a maximal dose of 21.8 Gy and a tumor margin dose of 11.5 Gy by using a mean of 4.5 isocenters. Final overall response rates were as follows: complete response 19.4%, partial response 67.4%, tumor control 79.6%, and tumor progression 20.4%. Reducing the tumor margin dose resulted in decreased therapeutic response and increased tumor progression, although the rate of visual and pituitary function loss also decreased. Among the factors examined, age (for adults) and the nature of the tumor (cystic or mixed) were statistically significant favorable and unfavorable prognostic factors, respectively. The actuarial 5- and 10-year survival rates were 94.1 and 91%, respectively. The progression-free survival rates were 60.8 and 53.8%, respectively. Patient outcomes were reportedly excellent in 45 cases, good in 23, fair in four, and poor in three; 16 patients died. Deterioration both in vision and endocrinological functions were documented as side effects in six patients (6.1%).


Stereotactic GKS is safe and effective, in the long term, as an adjuvant or boost therapy for residual or recurrent craniopharyngiomas after surgical removal and has minimal side effects. New treatment strategies must be devised to manage these tumors.

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Gamma knife surgery for trigeminal neuralgia: outcomes and prognostic factors

Jason Sheehan, Hung-Chuan Pan, Matei Stroila, and Ladislau Steiner

Object. Microvascular decompression (MVD) and percutaneous ablation surgery have historically been the treatments of choice for medically refractory trigeminal neuralgia (TN). Gamma knife surgery (GKS) has been used as an alternative, minimally invasive treatment in TN. In the present study, the authors evaluated the long-term results of GKS in the treatment of TN.

Methods. From 1996 to 2003, 151 cases of TN were treated with GKS. In this group, radiosurgery was performed once in 136 patients, twice in 14 patients, and three times in one patient. The types of TN were as follows: 122 patients with typical TN, three with atypical TN, four with multiple sclerosis—associated TN, and seven with TN and a history of a cavernous sinus tumor. In each case, the chosen radiosurgical target was located 2 to 4 mm anterior to the entry of the trigeminal nerve into the pons. The maximal radiation doses ranged from 50 to 90 Gy. The median age of the patients was 68 years (range 22–90 years), and the median time from diagnosis to GKS was 72 months (range 1–276 months). The median follow up was 19 months (range 2–96 months). Clinical outcomes and postradiosurgical magnetic resonance (MR) imaging studies were analyzed. Univariate and multivariate analyses were performed to evaluate factors that correlated with a favorable, pain-free outcome.

The mean time to relief of pain was 24 days (range 1–180 days). Forty-seven, 45, and 34% of patients were pain free without medication at the 1-, 2-, and 3-year follow ups, respectively. Ninety, 77, and 70% of patients experienced some improvement in pain at the 1-, 2-, and 3-year follow ups, respectively. Thirty-three (27%) of 122 patients with initial improvement subsequently experienced pain recurrence a median of 12 months (range 2–34 months) post-GKS. Among those whose symptoms recurred, 14 patients underwent additional GKS, six MVD, four glycerol injection, and one patient a percutaneous radiofrequency rhizotomy. Twelve patients (9%) suffered the onset of new facial numbness post-GKS. Changes on MR images post-GKS were noted in nine patients (7%). On univariate analysis, right-sided neuralgia (p = 0.0002) and a previous neurectomy (p = 0.04) correlated with a pain-free outcome; on multivariate analysis, both right-sided neuralgia (p = 0.032) and patient age (p = 0.05) were statistically significant. New onset of facial numbness following GKS correlated with undergoing more than one GKS (p = 0.002).

Conclusions. At the last follow up, GKS effected pain relief in 44% of patients. Some degree of pain improvement at 3 years post-GKS was noted in 70% of patients with TN. Although less effective than MVD, GKS remains a reasonable treatment option for those unwilling or unable to undergo more invasive surgical approaches and offers a low risk of side effects.

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Gamma knife surgery for vestibular schwannoma: 10-year experience of 195 cases

Wen-Yuh Chung, Kang-Du Liu, Cheng-Ying Shiau, Hsiu-Mei Wu, Ling-Wei Wang, Wan-Yuo Guo, Donald Ming-Tak Ho, and David Hung-Chi Pan

Object. The authors conducted a study to determine the optimal radiation dose for vestibular schwannoma (VS) and to examine the histopathology in cases of treatment failure for better understanding of the effects of irradiation.

Methods. A retrospective study was performed of 195 patients with VS; there were 113 female and 82 male patients whose mean age was 51 years (range 11–82 years). Seventy-two patients (37%) had undergone partial or total excision of their tumor prior to gamma knife surgery (GKS). The mean tumor volume was 4.1 cm3 (range 0.04–23.1 cm3). Multiisocenter dose planning placed a prescription dose of 11 to 18.2 Gy on the 50 to 94% isodose located at the tumor margin. Clinical and magnetic resonance (MR) imaging follow-up evaluations were performed every 6 months.

A loss of central enhancement was demonstrated on MR imaging in 69.5% of the patients. At the latest MR imaging assessment decreased or stable tumor volume was demonstrated in 93.6% of the patients. During a median follow-up period of 31 months resection was avoided in 96.8% of cases. Uncontrolled tumor swelling was noted in five patients at 3.5, 17, 24, 33, and 62 months after GKS, respectively. Twelve of 20 patients retained serviceable hearing. Two patients experienced a temporary facial palsy. Two patients developed a new trigeminal neuralgia. There was no treatment-related death. Histopathological examination of specimens in three cases (one at 62 months after GKS) revealed a long-lasting radiation effect on vessels inside the tumor.

Conclusions. Radiosurgery had a long-term radiation effect on VSs for up to 5 years. A margin 12-Gy dose with homogeneous distribution is effective in preventing tumor progression, while posing no serious threat to normal cranial nerve function.