Search

Background: Metastases to the brainstem portend a poor prognosis and present a challenge in clinical management. Surgical resection is rarely a viable option., Methods: Post-treatment MRI scans of patients with brainstem metastases treated with radiosurgery were used to determine local control and disease progression. Median survival was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model, respectively., Results: Thirty-two consecutive patients with brainstem metastasis underwent Gamma Knife radiosurgery. Median age was 50 years. Median tumor volume was 0.71 cm3 and median tumor margin dose was 13 Gy. Seventeen of 32 patients received WBRT prior to stereotactic radiosurgery. Median survival was 5.2 months. There was a statistically significant difference in survival based on RTOG recursive partition analysis (RPA) class. Median survival of patients categorized as RPA class I was 19.2 months, RPA class II was 8.4 months, and RPA class III was 1.9 months. The overall local tumor control rate was 87.5%. There were no acute complications following stereotactic radiosurgery and no evidence of radiation necrosis noted on post-treatment MRI scans., Conclusion: Stereotactic radiosurgery is an effective treatment for brainstem metastases and should be considered especially for patients with good performance status., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: The causes of failure after an initial Gamma procedure were studied, along with imaging and clinical outcomes, in a series of 140 patients with cerebral arteriovenous malformations (AVMs) treated with repeat Gamma Knife surgery (GKS)., Methods: Causes of initial treatment failure included inaccurate nidus definition in 14 patients, failure to fill part of the nidus as a result of hemodynamic factors in 16, recanalization of embolized AVM compartments in 6, and suboptimal dose (<20 Gy) in 23. Nineteen patients had repeat GKS for subtotal obliteration of AVMs. In 62 patients, the AVM failed to obliterate despite correct target definition and adequate dose. At the time of retreatment, the nidus volume ranged from 0.1 to 6.9 cm3 (mean, 1.4 cm3), and the mean prescription dose was 20.3 Gy., Results: Repeat GKS yielded a total angiographic obliteration in 77 patients (55%) and subtotal obliteration in 9 (6.4%). In 38 patients (27.1%), the AVMs remained patent, and in 16 patients (11.4%), no flow voids were observed on magnetic resonance imaging. Clinically, 126 patients improved or remained stable, and 14 experienced deterioration (8 resulting from a rebleed, 2 caused by persistent arteriovenous shunting, and 4 related to radiation-induced changes)., Conclusion: By using repeat GKS, we achieved a 55% angiographic cure rate. Although radiation-induced changes as visualized on magnetic resonance imaging occurred in 48 patients (39%), only 4 patients (3.6%) developed permanent neurological deficits. These findings may be useful in deciding the management of AVMs in whom total obliteration after initial GKS was not achieved.

Objective: This study evaluates the tumor histopathology and clinical characteristics of patients who underwent resection of their brain metastasis after failed gamma knife radiosurgery., Methods: This study was a retrospective review from a prospective database. A total of 1200 brain metastases in 912 patients were treated by gamma knife radiosurgery during a 7-year period. Fifteen patients (1.6% of patients, 1.2% of all brain metastases) underwent resective surgery for either presumed tumor progression (6 patients) or worsening neurological symptoms associated with increased mass effect (9 patients). Radiographic imaging, radiosurgical and surgical treatment parameters, histopathological findings, and long-term outcomes were reviewed for all patients., Results: The mean age at the time of radiosurgery was 57 years (age range, 32-65 years). Initial pathological diagnoses included metastatic non-small cell lung carcinoma in 8 patients (53%), melanoma in 4 patients (27%), renal cell carcinoma in 2 patients (13%), and squamous cell carcinoma of the tongue in 1 patient (7%). The mean time interval between radiosurgery and surgical extirpation was 8.5 months (range, 3 weeks to 34 months). The mean treatment volume for the resected lesion at the time of radiosurgery was 4.4 cm(3) (range, 0.6-8.4 cm(3)). The mean dose to the tumor margin was 21Gy (range, 18-24 Gy). In addition to the 15 tumors that were eventually resected, a total of 32 other metastases were treated synchronously, with a 78% control rate. The mean volume immediately before surgery for the 15 resected lesions was 7.5 cm(3) (range, 3.8-10.2 cm(3)). Histological findings after radiosurgery varied from case to case and included viable tumor, necrotic tumor, vascular hyalinization, hemosiderin-laden macrophages, reactive gliosis in surrounding brain tissue, and an elevated MIB-1 proliferation index in cases with viable tumor. The mean survival for patients in whom viable tumor was identified (9.4 months) was significantly lower than that of patients in whom only necrosis was seen (15.1 months; Fisher's exact test, P < 0.05)., Conclusion: Radiation necrosis and tumor radioresistance are the most common causes precipitating a need for surgical resection after radiosurgery in patients with brain metastasis.

Despite a randomized trial showing no benefit of stereotactic radiosurgery (SRS) prior to radiation therapy (RT), the benefits of SRS after RT and at the time of progression require further characterization. We retrospectively reviewed 48 patients with histopathological diagnoses of glioblastoma (GBM) that were treated with SRS over a 16-year period (1991-2007). Twenty-two were treated as part of their initial treatment paradigm and 26 were treated at the time of progression. The primary endpoints studied were overall survival (OS), survival after SRS and time-to-progression (TTP). Patients treated at the time of progression had significantly longer OS than those treated on initial presentation (17.4 vs. 15.1 months, P = 0.003). On multivariate analysis, Radiation Therapy Oncology Group (RTOG) class III patients, those with more extensive resections, and those who were not on steroids at the time of SRS had significantly improved OS. SRS margin dose was a significant prognostic factor for TTP on multivariate analysis (HR = 0.78, 95% CI: 0.62-0.98). In the subgroup of patients treated with GKS as part of their initial treatment, an increasing number of weeks between surgical resection and GKS was a poor prognostic factor on multivariate analysis (HR = 1.11, 95% CI: 1.01-1.23). In patients who were treated with SRS at the time of progression, chemotherapy was associated with a longer TTP (P = 0.028). Our results suggest that SRS provides a survival advantage when delivered after RT. This benefit may be best appreciated in RTOG class III patients. Moreover, SRS may be a viable alternative to open surgery for aggressive management of GBM at the time of recurrence. Prospective studies of SRS for GBM should focus on these two groups of patients.

Object: This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis., Methods: A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2-115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75-35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery., Results: The mean radiographic follow-up duration was 14 months (median 10 months, range 4-37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p=0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p=0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40-100)., Conclusion: Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Object: This study reviews the long-term clinical results of stereotactic radiosurgery in the treatment of pituitary adenoma patients., Methods: We reviewed the outcomes of 298 patients who underwent Gamma Knife radiosurgery for recurrent or residual pituitary adenomas. These results are compared to other contemporary radiosurgical series., Results: Pituitary tumors are well-suited for radiosurgery, since radiation can be focused on a well circumscribed region, while adjacent neural structures in the suprasellar and parasellar regions are spared. The overall rate of volume reduction following stereotactic radiosurgery is 85% for non-secretory adenomas that are followed for more than 1-year. The rates of hormonal normalization in patients with hypersecretory adenomas can vary considerably, and tends to be higher in patients with Cushing's Disease and acromegaly (remission rate of approximately 53% and 54%, respectively) when compared with patients who have prolactinomas (24% remission) and Nelson's syndrome (29%) remission. Advances in dose delivery and modulation of adenoma cells at the time of radiosurgery may further improve results., Conclusions: Although the effectiveness of radiosurgery varies considerably depending on the adenoma histopathology, volume, and radiation dose, most studies indicate that radiosurgery when combined with microsurgery is effective in controlling pituitary adenoma growth and hormone hypersecretion. Long-term follow-up is essential to determine the rate of endocrinopathy, visual dysfunction, hormonal recurrence, and adenoma volume control.

Objective: This study evaluates the safety and efficacy of gamma knife radiosurgery (GKRS) in patients with a growth hormone-secreting adenoma., Methods: A retrospective review of data collected from a prospective database of GKRS patients between January 1988 and September 2006 was performed in patients with acromegaly. Successful endocrine outcome was defined as normalization of the insulin-like growth factor level. Tumor volume was also assessed. At least 18 months of follow-up was available in 95 patients who received radiosurgery during the study period. Mean endocrine follow-up was 57 months (range, 18-168 mo)., Results: Normal insulin-like growth factor levels were achieved in 50 patients (53%) at an average time of 29.8 months after radiosurgery (median, 23.5 mo). A decrease in tumor volume control was achieved in 83 (92%) of 90 patients. Five patients (6%) had no change in tumor volume, and two patients (2%) had an increase in tumor volume. New endocrine deficiencies developed in 32 patients (34%). Four patients developed new-onset partial visual acuity deficits; three of these patients had received previous conventional fractionated radiation therapy., Conclusion: GKRS is a complementary treatment for recurrent or residual growth hormone-secreting pituitary adenomas. Although infrequent, tumor growth, new-onset pituitary hormone deficiency, recurrence, and neurological dysfunction require careful clinical, radiological, and endocrinological follow-up.

Intracranial radiosurgery has been proved effective for the treatment of brain metastasis. The treatment of paraspinal and spinal metastasis with spinal radiosurgery represents a natural extension of the principles of intracranial radiosurgery. However, spinal radiosurgery is a far more complicated process than intracranial radiosurgery. Larger treatment volumes, numerous organs at risk, and the inability to utilize rigid, frame-based immobilization all contribute to the substantially more complex process of spinal radiosurgery. Beyond the convenience of a shorter duration of treatment for the patient, spinal radiosurgery affords a greater biological equivalent dose to a metastatic lesion than conventional radiotherapy fractionation schemes. This appears to translate into a high rate of tumor control and fast pain relief for patients. The minimally invasive nature of this approach is consistent with trends in open spinal surgery and helps to maintain or improve a patient's quality of life. Spinal radiosurgery has expanded the neurosurgical treatment armamentarium for patients with spinal and paraspinal metastasis.

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.

Stereotactic radiosurgery is a neurosurgical modality in which a target lesion can be irradiated while sparing normal brain tissue. In some respects, brain metastasis is well suited for radiosurgery, as metastatic lesions tend to be small and well circumscribed and displace (but do not infiltrate) normal brain tissue, facilitating the delivery of radiation. Advances in stereotactic radiosurgical planning, such as blocking patterns and beam shaping, have allowed further targeting of discrete lesions while minimizing the effect of radiation toxicity on the central nervous system. In this paper the authors review the radiobiology of brain metastases and stereotactic radiosurgical approaches that can be used to treat these tumors safely.

Objective: Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas., Methods: We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up., Results: Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%)., Conclusion: Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

Pituitary adenomas are not just one of the most common intracranial tumors but also one of the most difficult to cure. Neurosurgeons have adapted their tools to include precise ionizing radiation in the form of the gamma knife to treat pituitary adenomas. The use of the gamma knife in the management of pituitary adenomas following microsurgery or in selected cases as a primary treatment is safe. The combined application of transsphenoidal surgery and Gamma Knife surgery is beneficial in many difficult cases. However in some patients, optimal control of tumor growth and normalization of hypersecretory states are not achieved. Innovative improvements in operative and radiosurgical techniques are required to avoid pituitary insufficiency and to reduce the number of the cases in which optimal radiosurgery is not feasible because of close tumor proximity to the optic pathways.

In this paper, we studied factors related to long-term survival after gamma knife radiosurgery (GKS) for primary and metastatic brain tumors. We examined all cases of brain metastases and malignant glioma treated with GKS between September 1994 and December 1998. All patients with survival exceeding 2 years were studied retrospectively using prospectively acquired data. A total of 22 patients, with an average age of 56, were identified, which accounts for 11% of the total patients treated during this time interval. Seventeen of 22 are still alive with a mean follow-up of 48 months. Sixteen patients had metastatic tumors, whereas 6 had a malignant glioma. Thirteen of 15 patients with metastases had a controlled primary site, and the other 2 patients did not have a primary site identified. These 2 patients were among the 3 that died during the follow-up period. Fourteen patients developed symptomatic radiation necrosis by MRI criteria with 4 confirmed by biopsy. Quality-of-life factors were assessed in 20 of 22 patients using a modified Spitzer scale, which showed a high level of functioning in all of the long-term survivors (mean score 8.65 of 10), and only 1 patient had a Karnofsky Performance Score of less than 70. We conclude that radiosurgery provides a noninvasive and effective way of controlling brain tumors, while preserving quality of life.