Integration of three-dimensional corticospinal tractography into treatment planning for gamma knife surgery

OBJECT: In the radiosurgical treatment of critically located lesions, the effort to minimize the risk of complication is essential. In this study the integration of diffusion-tensor (DT) imaging-based tractography was clinically applied to treatment planning for gamma knife surgery (GKS). METHODS: Seven patients with cerebral arteriovenous malformations located adjacent to the corticospinal tract (CST) underwent this technique. Data provided by DT imaging were acquired before the frame was affixed to the patient's head and the CST of the DT tractography was created using our original software. Stereotactic three-dimensional imaging studies were obtained after frame fixation and then coregistered with the data from DT tractography. After image fusion of the two studies, the combined images were transported to a GKS treatment-planning workstation. The spatial relationship between the dose distribution and the CST was clearly demonstrated within the 2 hours it took to complete the entire imaging process. The univariate logistic regression analysis of transient or permanent motor complications revealed a significant independent correlation with the volume of the CST that received 25 Gy or more and with a maximum dose to the CST (p < 0.05). CONCLUSIONS: The integration of DT tractography into the GKS treatment planning was highly useful in confirming the dose to the CST during treatment planning.     

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 to 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.     

Salvage treatment of distant recurrent brain metastases with Gamma Knife surgery

Background

The aim of the study was to analyze the results following salvage Gamma Knife® surgery (GKS) for distant recurrent brain metastases in patients previously treated with GKS for brain metastases.

Methods

Survival time and freedom from new distant recurrences (DR) were studied in 251 patients treated with salvage GKS for brain metastases that had developed following a first GKS. The patients were followed prospectively and the results related to a number of patient parameters as well as the results following the first GKS.

Results

The median survival time was 9.6 months, and the median time of freedom from developing DR was 7.5 months after salvage GKS. The survival time was unrelated to age, gender, prior WBRT, and primary disease. It was significantly longer in patients with a single DR at salvage GKS as compared to those with multiple ones (16 versus 8.3 months). Patients with 2–4 DRs lived longer than those with >4 lesions, 10 versus 5.8 months.The survival was significantly longer following salvage GKS as compared to following the first GKS. The prognosis of a patient with DR may therefore be less ominous than previously assumed. A classification system for DRs based on their clinical impact and treatability is therefore suggested.

Conclusions

The longer survival time following salvage GKS as compared to following the first GKS suggests that many patients benefit from salvage GKS. A classification system of DR is suggested to estimate its clinical impact.

     

Gamma Knife surgery for skull base chordomas and chondrosarcomas

OBJECT: The purpose of this study was to evaluate radiosurgical outcomes in skull base chordomas and chondrosarcomas, and to determine which tumors are appropriate for stereotactic radiosurgery as adjuvant therapy following maximum tumor resection. METHODS: Thirty-seven patients (48 lesions) were treated using Gamma Knife surgery (GKS); 27 had chordomas, seven had chondrosarcomas, and three had radiologically diagnosed chordomas. The mean tumor volume was 20 ml, and the mean maximum and marginal doses were 28 and 14 Gy, respectively. The mean follow-up period was 97 months from diagnosis and 59 months from GKS. RESULTS: The actuarial 5- and 10-year survival rates after GKS were 80 and 53%, respectively. The actuarial 5- and 10-year local tumor control (LTC) rates after single or multiple GKS sessions were 76 and 67%, respectively. All patients with low-grade chondrosarcomas achieved good LTC. A tumor volume of less than 20 ml significantly affected the high rate of LTC (p = 0.0182). No patient had adverse radiation effects, other than one in whom facial numbness worsened despite successful tumor control. CONCLUSIONS: As an adjuvant treatment after resection, GKS is a reasonable option for selected patients harboring skull base chordomas or chondrosarcomas with a residual tumor volume of less than 20 ml. Dose planning with a generous treatment volume to avoid marginal treatment failure should be made at a marginal dose of at least 15 Gy to achieve long-term tumor control.     

Ruptured pseudoaneurysm following Gamma Knife surgery for a vestibular schwannoma

A 75-year-old woman underwent Gamma Knife surgery (GKS) for a vestibular schwannoma. Eight years after GKS, she suffered sudden onset of headache. Computed tomography revealed diffuse subarachnoid hemorrhage around the cisterns of the posterior fossa. Right vertebral artery angiography showed an aneurysm arising from the lateral pontomedullary segment of the left anterior inferior cerebellar artery. The aneurysm was not located at a branching site. Trapping of the distal anterior inferior cerebellar artery aneurysm was performed, and the aneurysm was removed. The pathological features of this aneurysm are discussed. This aneurysm was diagnosed as a pseudoaneurysm pathologically. This is the first report of aneurysm formation with pathological findings following GKS for a vestibular schwannoma.     

Long-term outcomes of Gamma Knife surgery for cavernous sinus meningioma

OBJECT: The aim of this study was to evaluate long-term outcomes, including tumor control and neurological function, in patients with cavernous sinus meningiomas treated using Gamma Knife surgery (GKS). METHODS: One hundred fifteen patients with cavernous sinus meningiomas, excluding atypical or malignant meningiomas, were treated with GKS between 1991 and 2003. Forty-nine patients (43%) underwent GKS as the initial treatment. The mean tumor volume was 14 cm3, and the mean maximum and margin doses applied to the tumor were 27 and 13 Gy, respectively. The median follow-up period was 62 months. During the follow-up, 111 patients were able to be evaluated with neuroimaging. RESULTS: The actuarial 5- and 10-year progression-free survival rates were 87 and 73%, respectively. Similarly, the actuarial 5- and 10-year focal tumor control rates were 94 and 92%, respectively. Regarding functional outcomes, 43 patients (46%) experienced some degree of improvement, 40 (43%) remained stable, and 11 (12%) had worse preexisting or newly developed symptoms. Patients who underwent GKS as the initial treatment experienced significant improvement of their symptoms (p = 0.006). CONCLUSIONS: Gamma Knife surgery is a safe and effective treatment over the long term in selected patients with cavernous sinus meningiomas. Tumor progression is more likely to occur from the lesion margin outside the treatment volume. In small to medium-sized tumors, GKS is an excellent alternative to resection, preserving good neurological function. For relatively large-sized tumors, low-dose radiosurgery (< or = 12 Gy) is acceptable for the prevention of tumor progression.     

Gamma Knife surgery for arteriovenous malformations in the brain: integration of time-resolved contrast-enhanced magnetic resonance angiography into dosimetry planning. Technical note

OBJECT: The aim of this study was to develop an algorithm for the integration of time-resolved contrast-enhanced magnetic resonance (MR) angiography into dosimetry planning for Gamma Knife surgery (GKS) of arteriovenous malformations (AVMs) in the brain. METHODS: Twelve patients harboring brain AVMs referred for GKS underwent intraarterial digital subtraction (DS) angiography and time-resolved MR angiography while wearing an externally applied cranial stereotactic frame. Time-resolved MR angiography was performed on a 1.5-tesla MR unit (Achieva, Philips Medical Systems) using contrast-enhanced 3D fast field echo sequencing with stochastic central k-space ordering. Postprocessing with interactive data language (Research Systems, Inc.) produced hybrid data sets containing dynamic angiographic information and the MR markers necessary for stereotactic transformation. Image files were sent to the Leksell GammaPlan system (Elekta) for dosimetry planning. RESULTS: Stereotactic transformation of the hybrid data sets containing the time-resolved MR angiography information with automatic detection of the MR markers was possible in all 12 cases. The stereotactic coordinates of vascular structures predefined from time-resolved MR angiography matched with DS angiography data in all cases. In 10 patients dosimetry planning could be performed based on time-resolved MR angiography data. In two patients, time-resolved MR angiography data alone were considered insufficient. The target volumes showed a notable shift of centers between modalities. CONCLUSIONS: Integration of time-resolved MR angiography data into the Leksell GammaPlan system for patients with brain AVMs is feasible. The proposed algorithm seems concise and sufficiently robust for clinical application. The quality of the time-resolved MR angiography sequencing needs further improvement.     

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

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.     

Early brain tumor metastasis reduction following Gamma Knife surgery

OBJECT: Unlike whole-brain radiation therapy, Gamma Knife surgery (GKS) is delivered in a single session for the treatment of brain metastases. The extent to which GKS can facilitate early tumor control was the focus of this study. METHODS: The authors reviewed 134 metastatic lesions in 82 patients treated with GKS at the University of Virginia who underwent follow-up MR imaging within 30 days or less of GKS. For accurate volumetry only tumors measuring 0.5 cm3 or greater in volume were included. Radiological review as well as tumor volumetry was performed to assess the tumor's response to GKS. Tumors were characterized as either enlarged (> 15% volume increase), stable (follow-up volume +/- 15% of the initial volume), or decreased (> 15% volume decrease). A multivariate analysis was performed to determine factors related to each volume outcome group. RESULTS: Within the first month following GKS, a decrease was observed in 47.8% of the tumors. Tumor reduction varied according to carcinoma histopathological subtype, with 46.4% of non-small cell lung carcinomas, 70% of breast carcinomas, and 22.6% of melanomas showing volume reduction within 30 days after GKS. The mean volume decrease was 41.7%. For the remaining tumors, 41% were stable and 11.2% increased in volume. The overall analysis showed that there was a significant difference in percentage tumor change according to histopathological type (p < 0.001). There was a trend toward increased tumor reduction in those carcinoma types that are traditionally viewed as radiation sensitive (breast and non-small cell lung carcinomas). CONCLUSIONS: Gamma Knife surgery can offer patients early substantial volume reduction in many brain metastases. In instances in which early volume reduction of limited intracranial disease is desired, GKS may be used alone or before whole brain radiation therapy.     

Radionecrosis following Gamma Knife treatment for mesial temporal lobe epilepsy

A 24-year-old male patient was treated with Gamma Knife surgery (GKS) for medial temporal lobe epilepsy. The treatment parameters were in accordance with established practice. Epilepsy stopped after 2 years and medication was discontinued. Four years later, he developed a profound radionecrosis leading to blindness. As had refused surgical intervention his blindness has become permanent. As this is the second such case to be reported, it is considered a cause for concern, since microsurgery remains a safe alternative treatment. It is suggested that GKS for mesial temporal lobe epilepsy should be restricted to University centres of excellence as part of research projects under the control of ethics committees. It should not at present be considered to be a safe treatment for general use.