Successful treatment of glomus jugulare tumours with gamma knife radiosurgery: clinical and physical aspects of management and review of the literature

PURPOSE: To demonstrate the feasibility of treatment and early outcomes for patients treated with gamma knife radiosurgery (GKR), with or without surgical resection, for glomus jugulare tumours. METHODS: Between January 2007 and November 2008, 10 patients with glomus jugulare tumours were treated with GKR. Eight had prior surgical resection, seven subtotal resection and one total resection. In two cases GKR was the only definitive therapy. Baseline neurological deficits were prospectively recorded and present in 90% prior to GKR. The median tumour size and volume were 4 cc (0.7-10.9 cc). The median marginal tumour dose was 14 Gy (12-16 Gy). Clinical and radiographic outcomes are reported with a median follow-up of 9.7 months. RESULTS: Stereotactic frame placement allowed treatment of all 10 lesions, although 3-point fixation was sometimes required to avoid collisions. No patients developed worsening of symptoms or new neurological complaints after GKR; symptom relief was achieved in 50% of cases. No cases of clinical or radiographic progression were identified. Radiographically, 80% of lesions were stable and 20% showed significant shrinkage. CONCLUSIONS: GKR is an excellent option for patients with glomus jugulare tumours after complete or subtotal resection or at recurrence. Appropriately planned frame placement allows successful treatment delivery without difficulty. GKR improved symptoms, prevented neurological progression and achieved radiographic stability or regression in all cases (AU)

Gamma Knife radiosurgery for occipital condyle metastasis

We present a 45 year old female with right occipital condylar metastases who was treated at William Beaumont Hospital in the Gamma Knife Unit. Clinical results at 17 months follow-up and MRI are expose (AU)

Gamma Knife radiosurgery as a primary treatment option for solitary brain metastases from ovarian carcinoma.

We present three patients with brain metastasis cases from ovarian carcinoma (BMOC) treated at William Beaumont Hospital with a median follwow-up of 77 months and a mean survival after brain involvement of 23.66 months (range 5-44). Clinical and physical aspects are presented. Between December 2006 and August 2008, three cases of BMOC were treated using Gamma Knife (GK) radiosurgery. All patients had FIGO Stage III primary disease at initial diagnosis. Treatment sequences and features are described. GK achieves excellent local control of BMOC. Other parameters could be considered as biologically effective.

Gamma Knife radiosurgery as a primary treatment option for solitary brain metastases from ovarian carcinoma

We present three patients with brain metastasis cases from ovarian carcinoma (BMOC) treated at William Beaumont Hospital with a median follwow-up of 77 months and a mean survival after brain involvement of 23.66 months (range 5-44). Clinical and physical aspects are presented. Between December 2006 and August 2008, three cases of BMOC were treated using Gamma Knife (GK) radiosurgery. All patients had FIGO Stage III primary disease at initial diagnosis. Treatment sequences and features are described. GK achieves excellent local control of BMOC. Other parameters could be considered as biologically effective (AU)

Radiosurgery techniques and current devices.

Radiosurgery is a minimally invasive technique designed to elicit a specific radiobiologic response at the target tissue using focused ionizing radiation delivered in single procedure. Radiosurgery was originally devised to treat intracranial lesions by delivering a high dose of radiation precisely at the intracranial target using stereotactic guidance. The term was coined and the field defined by Lars Leksell, a visionary leader of neurosurgery at the Karolinska Institute in Stockholm. Refinements in stereotactic methodologies, major improvements in dose planning software, and advances in neurodiagnostic imaging, all facilitated the increasingly broad application of brain radiosurgical methodologies. New technologies have continued to evolve and are still emerging. A variety of different radiosurgery techniques have been developed during the past 4 decades. Radiosurgery is now being used even for extracranial lesions such as spinal tumors, lung, liver, and prostate pathologies. Numerous studies have examined the benefits and risks of radiosurgery performed with various devices. The long-term results of radiosurgery are now available and have established it as an effective noninvasive management strategy for many brain disorders. Radiosurgery is now considered a mainstream neurosurgical modality for treatment of vascular malformations, tumors, trigeminal neuralgia, movement disorders, and perhaps epilepsy. Its role as a tool for spine and body surgery is also under evaluation.

Tube angulation improves angiographic targeting of arteriovenous malformations during stereotactic radiosurgery.

Stereotactic radiosurgery using the 201 Cobalt-60 source Gamma Knife has been an effective method for obliterating selected cerebral arteriovenous malformations (AVMs). For more than 20,000 patients worldwide, angiography under stereotactic conditions has been the main imaging modality for defining and targeting the AVM nidus. The role of angulation of the X-ray tube for angiographic localization of the AVM during stereotactic Gamma Knife radiosurgery was studied with a phantom. Using current dose-planning software, tube angulation facilitated target visualization, improved three-dimensional dose planning, and has been consistent with the increased probability of complete nidus obliteration.

Dose reduction improves hearing preservation rates after intracanalicular acoustic tumor radiosurgery.

OBJECTIVE: To assess the potential for long-term serviceable hearing preservation in intracanalicular acoustic tumor patients who underwent stereotactic radiosurgery. METHODS: Between August 1987 and December 1997, 29 patients with intracanalicular acoustic tumors underwent stereotactic radiosurgery at our center using the Leksell gamma knife (Elekta Instruments, Inc., Atlanta, GA). Fifteen assessable patients had serviceable preradiosurgery hearing (pure tone average, < or = 50 dB; speech discrimination score, > or = 50%). We retrospectively analyzed our hearing results and compared hearing preservation in patients who received a minimal tumor dose of 14 Gy or less versus those who received more than 14 Gy to the tumor margin. RESULTS: No perioperative patient morbidity or mortality was observed. Serviceable hearing was preserved in 11 (73%) of 15 assessable patients (actuarial rate, 65%). Long-term follow-up demonstrated serviceable hearing preservation in 10 (100%) of 10 patients who received marginal tumor doses of 14 Gy or less but in only one of five patients who received more than 14 Gy. Preradiosurgery Gardner-Robertson class was preserved in 49%, and testable hearing was present in 68% of patients who had any testable hearing at presentation. Five patients demonstrated improvement in hearing (three had serviceable and two had nonserviceable hearing before radiosurgery). No patient developed a facial or trigeminal neuropathy. Seven of 13 patients with preoperative tinnitus continued to experience tinnitus in follow-up. Episodic vertigo continued in 3 of the 11 patients who presented with vertigo. CONCLUSION: Gamma knife radiosurgery (using conformal dose planning, small-beam geometry, and < or = 14 Gy to the margin) prevents tumor growth and achieves excellent hearing preservation rates.

A novel 675.2 nm diode laser densitometer for use with GafChromic films.

In this article we compare the accuracy of a diode laser densitometer emitting 675.2 nm to that of a commercial He-Ne laser densitometer emitting 632.8 nm for GafChromic MD-55 film readout. A Leksell gamma unit (AB Elekta Stockholm, Sweden) Model B with a 14 and 8 mm collimator at the same isocenter (combined 11 mm collimator) was used to irradiate GafChromic MD-55 films. Dose response curves, dose cross profile and FWHM were measured with a custom-designed diode laser scanning device, emitting light at 675.2 nm. The same data were recorded with a commercial He-Ne laser densitometer (PTW FIPS Plus, Freiburg, Germany), emitting light at 632.8 nm. Both measurements were compared to dose cross profiles of a radiosurgery dose planning program (GammaPlan 5.12, Elekta, Sweden). Compared to the commercial He-Ne laser densitometer, the custom-designed diode laser scanning device showed better agreement with the calculated dose cross profile. For two axes, the full width half maxima (FWHM) of the diode laser scanning device was within 0.1 mm deviation compared to the data calculated by the dose planning program. The FWHM of the commercial He-Ne laser densitometer was less accurate (1.6 and 2.1 mm deviation). Our data show that a diode laser scanning device using a light source emitting 675.2 nm increases the accuracy of a GafChromic MD-55 film readout. This greater accuracy may be related to the diode laser measuring the optical density close to maximum absorption of the GafChromic film MD-55 (671-675 nm).

Stereotactic radiosurgery in the management of acoustic neuromas associated with neurofibromatosis Type 2.

OBJECT: Stereotactically guided radiosurgery is one of the primary treatment modalities for patients with acoustic neuromas (vestibular schwannomas). The goal of radiosurgery is to arrest tumor growth while preserving neurological function. Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2) represent a special challenge because of the risk of complete deafness. To define better the tumor control rate and long-term functional outcome, the authors reviewed their 10-year experience in treating these lesions. METHODS: Forty patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35 of them for solitary tumors. The other five underwent staged procedures for bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors) had undergone a median of two prior resections. The mean tumor volume at radiosurgery was 4.8 ml, and the mean tumor margin dose was 15 Gy (range 12-20 Gy). The overall tumor control rate was 98%. During the median follow-up period of 36 months, 16 tumors (36%) regressed, 28 (62%) remained unchanged, and one (2%) grew. In the 10 patients for whom more than 5 years of clinical and neuroimaging follow-up results were available (median 92 months), five tumors were smaller and five remained unchanged. Surgical resection was performed in three patients (7%) after radiosurgery; only one showed radiographic evidence of progression. Useful hearing (Gardner-Robertson Class I or II) was preserved in six (43%) of 14 patients, and this rate improved to 67% after modifications made in 1992. Normal facial nerve function (House-Brackmann Grade 1) was preserved in 25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34 (94%) of 36 patients. CONCLUSIONS: Stereotactically guided radiosurgery is a safe and effective treatment for patients with acoustic tumors in the setting of NF2. The rate of hearing preservation may be better with radiosurgery than with other available techniques.

Can hearing improve after acoustic tumor radiosurgery?

Advances in noninvasive diagnostic techniques have enabled physicians to diagnose acoustic tumors early, while hearing is still present. Applications of advanced operative techniques have allowed surgeons to decrease progressively the operative mortality to virtually zero, to save facial nerve function in a large number of patients, and even to preserve serviceable hearing in selected patients. Documented improvement in hearing after acoustic tumor surgery is rare. During the last decade, stereotactic radiosurgery has evolved as a noninvasive surgical option for acoustic tumors. Hearing improvement after radiosurgery has not been reported. The authors observed hearing improvement in 21 out of 487 patients who had radiosurgery during a 10-year interval. This article reviews their experience of hearing improvement after radiosurgery and suggests possible reasons that hearing can not only be retained but also improved in selected patients.

Treatment planning of stereotactic convergent gamma-ray irradiation using Co-60 sources.

The basic features of the convergent Co-60 gamma-ray unit, known as Gamma Knife and the standard procedures of treatment planning for various cases in general have been described in details. The new generation of the rotating gamma system and the future clinical applications are briefly mentioned.

Black holes, white dwarfs and supernovas: imaging after radiosurgery.

PURPOSE: To evaluate the imaging and pathological correlates of successful or risk-related stereotactic radiosurgery (SR). Methods and Materials. The ten-year Gamma Knife experience in 2,344 patients at the University of Pittsburgh was reviewed. In addition, the results or radiosurgery primate, rat, and mouse models were analyzed. Successful results and untoward complications were evaluated. RESULTS: Dose, volume, location and histology affected the imaging changes seen after SR. Imaging changes range from central loss of contrast ('black holes'), shrinkage with diffuse contrast uptake ('white dwarfs'), or stabilization or growth arrest. Limited pathological data indicates that the prevention of cell division coupled with vascular obliteration results in tumor control, whereas a progressive endothelial proliferative and obliterative response results in arteriovenous malformation (AVM) obliteration. Perilesional imaging changes, especially in vascular malformations, may reflect flow phenomena, interstitial edema, or profound reactive astrocytosis ('supernovas'). CONCLUSION: Imaging changes correlate with both success and risks of stereotactic radiosurgery; however, pathological correlates are limited. High resolution neurodiagnostic imaging provides the best quality control available to assess the response to stereotactic radiosurgery. In the future, additional molecular probes are necessary to assess the radiobiological effects of radiosurgery.

Factors associated with successful arteriovenous malformation radiosurgery.

OBJECTIVE: To analyze the clinical and angiographic variables that affect the results of arteriovenous malformation (AVM) radiosurgery and to propose a new method of reporting patient outcomes after AVM radiosurgery. This method incorporates both the obliteration status of the AVMs and the postoperative neurological condition of the patient. METHODS: Patient outcomes were defined as excellent (nidus obliteration and no new deficits), good (nidus obliteration with a new minor deficit), fair (nidus obliteration with a new major deficit), unchanged (incomplete nidus obliteration without a new deficit), poor (incomplete nidus obliteration with any new deficit), and dead. Two hundred twenty patients who underwent AVM radiosurgery at our center before 1992 were subjected to a multivariate analysis with patient outcomes as the dependent variable. RESULTS: Multivariate analysis determined four factors associated with successful AVM radiosurgery: smaller AVM volume (P=0.003), number of draining veins (P=0.001), younger patient age (P=0.0003), and hemispheric AVM location (P=0.002). Preradiosurgical embolization was a negative predictor of successful AVM radiosurgery (P=0.02). CONCLUSION: AVM obliteration without new neurological deficits can be achieved in at least 80% of patients with small volume, hemispheric AVMs after single-session AVM radiosurgery. Future studies on AVM radiosurgery should report patient outcomes in a fashion that incorporates all the factors involved in successful AVM radiosurgery.

Management of petroclival meningiomas by stereotactic radiosurgery.

OBJECTIVE: To evaluate the role of stereotactic radiosurgery in the management of petroclival meningiomas, we retrospectively reviewed our experience with 62 patients managed at the University of Pittsburgh during an 8-year period. METHODS: All patients had cranial base meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. Some tumors extended into the cavernous sinus. Each of 39 patients (63%) had previously undergone one or more attempts at surgical resection. Seven patients (11%) had received fractionated external beam radiation therapy. Using the gamma knife, conformal multiple isocenter radiosurgery was performed with tumor margin doses of 11 to 20 Gy. RESULTS: During the median follow-up period of 37 months, neurological statuses improved in 13 patients (21%), remained stable in 41 patients (66%), and eventually worsened in 8 patients (13%). Tumor volumes decreased in 14 patients (23%), remained stable in 42 patients (68%), and increased in 5 patients (8%). Despite the proximity of these tumors to critical neural and vascular structures, complications resulting from radiosurgery were rare. Five patients (8%) developed new cranial nerve deficits within 24 months of radiosurgery, although none had evidence of tumor progression. These deficits resolved completely in two patients within 6 months of onset. CONCLUSION: Although an even longer follow-up period is desirable, we conclude that stereotactic radiosurgery provides a safe and effective management strategy for petroclival meningiomas, both as a primary procedure and as an adjunct to incomplete resection.

Analysis of neurological sequelae from radiosurgery of arteriovenous malformations: how location affects outcome.

PURPOSE/OBJECTIVE: To elucidate how the risks of developing temporary and permanent neurological sequelae from radiosurgery for arteriovenous malformations (AVM) are related to AVM location, the addition of stereotactic magnetic resonance (MR) imaging to angiographic targeting, and prior hemorrhage or neurological deficits. MATERIALS AND METHODS: We evaluated follow-up imaging and clinical data in 332 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1994. All patients had regular clinical or imaging follow-up for a minimum of 2 years (range: 24-96 months, median = 45 months). There were 83 patients with MR-assisted planning, 187 with prior hemorrhages, and 143 with prior neurological deficits. RESULTS: Symptomatic postradiosurgery sequelae (any neurological problem including headache) developed in 30 (9%) of 332 patients. Symptoms resolved in 58% of patients within 27 months with a significantly greater proportion (p = 0.006) resolving in patients with Dmin < 20 Gy vs. > or = 20 Gy (89 vs. 36%). The 7-year actuarial rate for developing persistent symptomatic sequelae was 3.8%. We first evaluated the relative risks for different locations to construct a postradiosurgery injury expression (PIE) score for AVM location. Multivariate logistic regression analysis of symptomatic postradiosurgery sequelae identified independent significant correlations with PIE location score (p = 0.0007) and 12 Gy volume (p = 0.008), but with none of the other factors tested (p > 0.3), including the addition of MR targeting, average radiation dose in 20 cc, prior hemorrhage, or neurological deficit. We used these results to construct a risk prediction model for symptomatic postradiosurgery sequelae. The risk of radiation necrosis was significantly correlated with PIE score (p < 0.048), but not with 12-Gy volume. CONCLUSION: The risks of developing complications from AVM radiosurgery can be predicted according to location with the PIE score, in conjunction with the 12-Gy treatment volume. Further study of factors affecting persistence of these sequelae (progression to radiation necrosis) is needed.

Radioprotective effects of the 21-aminosteroid U-74389G for stereotactic radiosurgery.

OBJECTIVE: Future improvements in the results of stereotactic radiosurgery will be related to better patient selection, dose planning, radiosensitization of the target, and, possibly, protection of the brain surrounding the target. 21-Aminosteroids may provide protection against brain radiation injury by inhibition of lipid peroxidation and a selective action on vascular endothelium. We hypothesized that the 21-aminosteroid U-74389G would reduce radiosurgery-related brain injury without attenuating the target volume response. METHODS: One hundred and forty-five rats were divided into four experimental groups before undergoing radiosurgery: control (n = 47); low-dose U-74389G (5 mg/kg of body weight, n = 30); high-dose U-74389G (15 mg/kg, n = 20); and methylprednisolone (2 mg/kg, n = 48). The drug was administered 1 hour before radiosurgery (4-mm gamma knife collimator) of the normal rat frontal lobe (single-fraction maximum doses of 50, 100, or 150 Gy) was performed. All brains underwent histological examination at 90 or 150 days to evaluate the diameters of necrosis and the findings of radiation-induced vasculopathy, brain edema, and gliosis. RESULTS: None of the animals that received 50-Gy radiation developed histological changes, whereas all of the animals that received 150-Gy radiation developed radiation necrosis without drug-induced protection from vascular changes or edema. In animals receiving 100-Gy radiation, high-dose aminosteroid reduced radiation-induced vasculopathy at 90 days (P = 0.06) and at 150 days (P = 0.02) and prevented regional edema at 90 days (P = 0.01) and at 150 days (P = 0.03). Low-dose aminosteroid and corticosteroid provided no protection. CONCLUSION: The 21-aminosteroid U-74389G provided protection after a single intravenously administered dose of 15 mg/kg against radiation-induced vasculopathy and edema. High-dose 21-aminosteroids seem to have optimal properties for radiosurgery, surrounding brain protection without reducing the therapeutic effect desired within the target volume.

Complications from arteriovenous malformation radiosurgery: multivariate analysis and risk modeling.

PURPOSE/OBJECTIVE: To assess the relationships of radiosurgery treatment parameters to the development of complications from radiosurgery for arteriovenous malformations (AVM). METHODS AND MATERIALS: We evaluated follow-up imaging and clinical data in 307 AVM patients who received gamma knife radiosurgery at the University of Pittsburgh between 1987 and 1993. All patients had regular clinical or imaging follow up for a minimum of 2 years (range: 24-96 months, median = 44 months). RESULTS: Post-radiosurgical imaging (PRI) changes developed in 30.5% of patients with regular follow-up magnetic resonance imaging, and were symptomatic in 10.7% of all patients at 7 years. PRI changes resolved within 3 years developed significantly less often (p = 0.0274) in patients with symptoms (52.8%) compared to asymptomatic patients (94.8%). The 7-year actuarial rate for developing persistent symptomatic PRI changes was 5.05%. Multivariate logistic regression modeling found that the 12 Gy volume was the only independent variable that correlated significantly with PRI changes (p < 0.0001) while symptomatic PRI changes were correlated with both 12 Gy volume (p = 0.0013) and AVM location (p = 0.0066). CONCLUSION: Complications from AVM radiosurgery can be predicted with a statistical model relating the risks of developing symptomatic post-radiosurgical imaging changes to 12 Gy treatment volume and location.

Hemangioblastoma of the posterior fossa. The role of multimodality treatment.

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.

Radiosurgery and fractionated radiation therapy: comparison of different techniques in an in vivo rat glioma model.

To identify histological changes and effects on survival in rats harboring C6 gliomas, the authors compared radiosurgery to different fractionated radiation therapy regimens including doses of calculated biological equivalence. Rats were randomized to control (54 animals) or treatment groups after implantation of C6 glioma cells into the right frontal brain region. At 14 days, treated rats underwent stereotactic radiosurgery (35 Gy to tumor margin; 22 animals), whole-brain radiation therapy (WBRT) (20 Gy in five fractions; 18 animals), radiosurgery plus WBRT (13 animals), hemibrain radiation therapy (85 Gy in 10 fractions; 16 animals) or single-fraction hemibrain irradiation (35 Gy; 10 animals). When compared to the control group (median survival 22 days), prolonged survival was identified after radiosurgery (p < 0.0001), radiosurgery plus WBRT (p < 0.0001), WBRT alone (p = 0.0002), hemibrain radiation therapy to 85 Gy (p < 0.0001), and 35-Gy hemibrain single-fraction irradiation (p = 0.004). Compared to the control group (mean tumor diameter, 6.8 mm), the tumor size was reduced in all treatment groups except WBRT alone. Reduced tumor cell density was exhibited in rats that underwent radiosurgery (p = 0.006) and radiosurgery plus WBRT (p = 0.009) when compared with rats in the control group, a finding not observed after any fractionated regimen. Increased intratumoral edema was identified after radiosurgery (p = 0.03) and combined treatment (p = 0.05), but not after fractionated radiation therapy or 35-Gy single-fraction hemibrain irradiation. In this animal model, the addition of radiosurgery significantly increased tumor cytotoxicity, potentially at the expense of radiation effects to regional brain. We found no difference in survival benefit or tumor diameter in animals that underwent radiosurgery compared to the calculated biologically equivalent regimen of 10-fraction radiation therapy to 85 Gy. The histological responses after radiosurgery were generally greater than those achieved with biologically equivalent doses of fractionated radiation therapy.