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.

Potential human error in setting stereotactic coordinates for radiosurgery: implications for quality assurance.

PURPOSE: The error frequency in setting stereotactic coordinates for gamma knife radiosurgery was investigated to determine what quality assurance safeguards are necessary. METHODS AND MATERIALS: A prospective study of 200 consecutive isocenter settings for gamma knife radiosurgery was analyzed to identify the frequency of spontaneous errors in setting and checking stereotactic coordinates (corrected prior to treatment). An additional 25 coordinate errors were introduced at random among the next 200 consecutive isocenter settings to provide additional data on identification of errors. RESULTS: Stereotactic coordinates required resetting in 12% (24/200) of the isocenters treated due to errors of 0.25-0.50 mm (8%) and 1-20 mm (4%). This comprised 2.2% (26/1200) of the individual coordinate settings. The frequency of these errors was significantly related to the specific directional coordinate set (p = 0.0004) and experience (p = 0.016). Errors were identified by 83.5% (91/109) of the observers checking the settings (60.0% of 0.25 mm errors, 94.6% of errors > or = 0.5 mm, p = 0.0000). Verification of stereotactic coordinates by two observers reduces the probability of an undetected error > or = 0.25 mm to 1/1,392 and to 1/154,712 for errors > or = 1 mm. CONCLUSION: Errors in setting stereotactic coordinates are common (12% prior to checking) but are corrected with a high degree of confidence by a quality assurance policy requiring coordinate verification by a minimum of two observers.

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.

Treatment planning for gamma knife radiosurgery with multiple isocenters.

Many arteriovenous malformations and tumors suitable for radiosurgical treatment have non-spherical or irregular shapes. Forty-eight percent of the first 156 patients treated with the gamma unit at the University of Pittsburgh required treatment with two or more isocenters to optimize dose distributions. Dose distributions for combining gamma knife treatments to two or more isocenters were systematically investigated. High speed computerized dosimetry was performed using specially developed software and dose distributions were confirmed with film densitometry. We have developed guidelines for treatment to two or more isocenters which help reduce treatment planning time, and facilitate selection of treatment doses and optimum dose distributions. These guidelines include maintaining an account of the distances between all isocenters, using a catalogue of sample two-isocenter isodose plans, comparing dose volume histograms, and calculating complication probabilities using the integrated logistic formula.

Shielding requirements on-site loading and acceptance testing on the Leksell gamma knife.

On August 14, 1987, the first stereotactic radiosurgical procedure using the gamma knife was performed in North America. Located in a self-contained radiosurgical suite in the basement of Presbyterian-University Hospital in Pittsburgh, Pennsylvania. This device uses 201 highly focused beams 60Co for the single-treatment closed-skull irradiation of brain lesions localized by stereotactic techniques (radiosurgery). One hundred and fifty-two patients with intracranial arteriovenous malformations or brain tumors were treated in the first year of operation. The Presbyterian University Hospital of Pittsburgh gamma knife is the first such unit in which the 60Co sources were loaded on-site. This effort required us to solve some difficult and unusual problems encountered during site preparation, delivery, and loading of the unit in a busy hospital setting. The solutions developed enabled installation and use of the gamma knife with minimal disruption of hospital activities while maintaining acceptable levels of exposure to radiation. Environmental surveys performed during the loading of the 201 radioactive sources (total, 219 TBq) confirmed that on-site loading is possible and practical. Our experience in the design, construction, and implementation of the first North American gamma knife supports the practicality and safety of on-site loading and may be of value in the planning and development of future gamma knife installations.

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.

Quality assurance for gamma knife stereotactic radiosurgery.

PURPOSE: This quality assurance program is designed for stereotactic radiosurgical units, gamma knife, to check and maintain the unit to preclude accidents and comply with current regulations. MATERIALS AND METHODS: Over 58 stereotactic radiosurgical units using 201 focused 60Co beams have been installed in the last 7 years and are in use at hospitals throughout the world, with at least 11 additional units being prepared to come on-line in the next year. This system has been in use at the University of Pittsburgh Medical Center (UPMC) for 7 years. A comprehensive quality assurance program has been developed. It includes the physics and dosimetry parameters and safety checks required by regulatory agencies. The program, based on over 7 years of experience in measurements, and used during the treatment of over 1500 patients, is separated into three aspects, namely physics, dosimetry, and safety. The UPMC program hopefully will indicate out-of-tolerance problems. Some quality assurance items are checked on a daily basis prior to patient treatment, while other aspects are checked on a weekly, monthly, and/or annual basis. A complete list of items with their respective time tables and tolerances is provided. RESULTS: Although experience shows very small margins of error, larger values were chosen to account for variations in equipment and techniques. CONCLUSIONS: Items included in this quality assurance program should indicate and/or preclude problems encountered in the use of this unit.

Treatment volume shaping with selective beam blocking using the Leksell gamma unit.

The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.

Physics of gamma knife approach on convergent beams in stereotactic radiosurgery.

The Presbyterian-University Hospital of Pittsburgh installed the first clinically designated Leksell gamma knife in the U.S. in August 1987. Gamma knife radiosurgery involves stereotactic target localization with the Leksell frame and subsequent closed-skull single-treatment session irradiation of a lesion with multiple highly focused gamma ray beams produced from 60Co sources. The hemispherical array of sources, the large number of small-diameter beams, and the steep dose gradients surrounding a targeted lesion make physical characterization of the radiation field complex. This paper describes the physical features and the operation of the gamma knife as well as the calibration procedures of the very small, well-collimated beams. The results of studies using in-phantom ion chamber, diode, film, and lithium fluoride thermoluminescent dosimetry were all in close agreement. Both single-beam and multiple-beam dose profiles were measured and reported for the interchangeable helmets, which have 4-, 8-, 14-, and 18-mm-diameter collimators. We also describe the dose calculation and treatment planning algorithm in the treatment planning system. Measurements of the accuracy of mechanical and radiation alignment are also performed and discussed.

Radiosurgery and brain tolerance: an analysis of neurodiagnostic imaging changes after gamma knife radiosurgery for arteriovenous malformations.

In order to analyze complications and the factors responsible for the development of serial imaging changes after stereotactic radiosurgery for intracranial arteriovenous malformations, we reviewed serial post-treatment magnetic resonance imaging scans in 72 patients. Median follow-up was 23 months (range 12 to 35 months). Twenty patients developed post-radiosurgical imaging changes consisting of new regions of increased T2 signal on magnetic resonance imaging in brain surrounding the arteriovenous malformation (two year actuarial incidence of 31%). Imaging changes were associated with headache or new neurological deficits in nine of these 20 (45%) and remained asymptomatic in 11 (55%). Symptoms developed in three of 13 patients with imaging changes in the cerebral cortex or cerebellum, in contrast to six of seven patients who had symptoms with imaging changes in the brainstem (p = .028). The onset of imaging changes varied from five to 18 months after radiosurgery (median, 12 months). Serial follow-up scans four to 25 months after the onset of imaging changes were available for review in 16 patients. Post-radiosurgical imaging changes completely resolved within 4 to 19 months in ten patients and have not yet completely resolved after 6 to 25 months in six patients. The projected actuarial rate for resolution of imaging changes was 88%, 19 months after onset; the median time for resolution was 14 months. Univariate analysis revealed that the development of imaging changes was significantly associated with treatment volume (p = .025), the risk predicted from the integrated logistic formula (p = .042), and the number of isocenters treated (p = .042). In multivariate analysis, volume was the only factor significantly associated with the development of imaging changes.

Separation of dose-gradient effect from beam-hardening effect on wedge factors in photon fields.

It is known experimentally that a wedge transmission factor depends upon the field size and depth of measurement in particular. Dependence of the transmission upon depth has been attributed to a hardening of the incident beam through the filter, which preferentially absorbs the low-energy photon of the bremsstrahlung component of that beam. We have attempted to separate this hardening effect from that of increased phantom scatter due to dose gradient induced by the wedge filter. Using an experimental wedge machined from cerrobend, the filter transmission at depth is measured and redefined relative to an "equally hardened" beam, obtained by filtering through a flat slab of equal thickness at the center of the wedge. Results of the Co-60, 4-, and 8-MV wedged beams indicate that nearly half of the increase in the transmission at depth is due to the effect of dose-gradient scatter in polystyrene phantom. Based on a simple relationship between primary and scattering radiation, an algebraic presentation is indeed in support of the dose gradient resulting in apparent increase in the wedge factors, at depth.

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).

The use of a radiochromic detector for the determination of stereotactic radiosurgery dose characteristics.

The measurement of absorbed dose as well as dose distributions (profiles and isodose curves) for small radiation fields (as encountered in stereotactic surgery) has been difficult due to the usual large detector size or densitometer aperture (> 1 mm) relative to the radiation field (as small as 4 mm). The radiochromic direct-imaging film, when read with a scanning laser microdensitometer (laser beam diameter 0.1 mm), overcomes this difficulty and has advantages over conventional film in providing improved precision, better tissue equivalence, greater dynamic range, higher spatial resolution, and room light handling. As a demonstration of suitability, the calibrated radiochromic film has been used to measure the dose characteristics for the 18-, 14-, 8-, and 4-mm fields from the gamma-ray stereotactic surgery units at Mayo Clinic and the University of Pittsburgh. Intercomparisons of radiochromic film with conventional methods of dosimetry and vendor-supplied computational dose planning system values indicate agreement to within +/- 2%. The dose, dose profiles, and isodose curves obtained with radiochromic film can provide high-spatial-resolution information of value for acceptance testing and quality control of dose measurement and/or calculation.

Stereotactic radiosurgery of the brain using the first United States 201 cobalt-60 source gamma knife.

The first United States 201 cobalt-60 source gamma knife for stereotactic radiosurgery of brain tumors and arteriovenous malformations became operational at the University of Pittsburgh on August 14, 1987. Four and one-half years of intensive planning, regulatory agency review, and analysis of published results preceded the first radiosurgical procedure. Installation of this 18,000-kg device and loading of the 201 cobalt-60 sources posed major challenges in engineering, architecture, and radiophysics. In the first 4 months of operation, we treated 52 patients (29 with arteriovenous malformations, 19 with extra-axial neoplasms of the skull base, and 4 with intra-axial malignant tumors). Most patients either had lesions considered "inoperable" or had residual lesions after attempted surgical resection. Neither surgical mortality nor significant morbidity was associated with gamma knife radiosurgery. As compared with treatment by conventional intracranial surgery (craniotomy), the average length of stay for radiosurgery was reduced by 4 to 14 days, and hospital charges were reduced by as much as 65%. Based on both the previously published results of treatment of more than 2,000 patients worldwide and on our initial clinical experience, we believe that gamma knife stereotactic radiosurgery is a therapeutically effective and economically sound alternative to more conventional neurosurgical procedures, in selected cases.

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.

Radiobiology of radiosurgery: Part I. The normal rat brain model.

Because limited histological information is available from clinical radiosurgical experience, animal investigations are needed to answer questions regarding the biological response of both normal and pathological tissues. To determine the radiosurgical dose-response relationship of normal brain, we irradiated the right frontal lobe of 18 rats with a single 4-mm isocenter of stereotactic irradiation using the 201-source 60Co gamma unit. Maximal single-fraction doses varied from 30 to 200 Gy (2 rats per dose). All animals were observed for 90 days, killed, and histologically examined. No animal developed neurological dysfunction during that interval, regardless of dose. Animals that received 30, 40, 50, or 60 Gy had no pathological changes. In those given 70 Gy, we found occasional shrunken neurons, and at 80 Gy, rare arteriolar wall thickening. One animal that received 100 Gy had marked capillary endothelial cell degeneration and protein extravasation in the target volume, and the other had a 4-mm diameter necrotic region. Circumscribed cerebral necrosis also was identified in all 4 rats treated with either 150 or 200 Gy; astrocytosis, edema, and microhemorrhage were noted within the surrounding 1 to 2 mm of adjacent brain, and tissue outside that volume had a more normal appearance. We constructed a dose-response relationship based on the cellular, spatial, and temporal effects of focused single-fraction irradiation of the rat brain. To determine the temporal evolution of a known necrotic lesion (200 Gy), 12 other animals were killed (2 each) 1, 7, 14, 21, 30, or 60 days after radiosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Preservation of cranial nerve function after radiosurgery for nonacoustic schwannomas.

Microsurgical resection is the primary management approach for patients with intracranial schwannomas. Recent studies have demonstrated that stereotactic radiosurgery is an effective therapeutic modality for patients with acoustic schwannomas. To define the role of radiosurgery in the management of patients with nonacoustic schwannomas, we reviewed the results of gamma unit stereotactic radiosurgery in six patients with trigeminal and five patients with jugular foramen region schwannomas. No patient with a trigeminal schwannoma demonstrated tumor growth during a mean follow-up of 21 months (range, 7-35 mo), whereas one patient with a jugular foramen region schwannoma had an increase in tumor size 7 months after radiosurgery. No new cranial nerve or brain stem deficits were noted in either patient group after radiosurgery. In this early experience, radiosurgery proved an effective primary or adjuvant technique for selected patients with schwannomas of the trigeminal, glossopharyngeal, or vagus nerves. Using our described method, the safety of radiosurgery was demonstrated on the brain stem, regional cranial nerves, and especially those cranial nerves intimately associated with the tumor.

Radiobiology of radiosurgery: Part II. The rat C6 glioma model.

We developed an experimental animal model to evaluate the potential role of stereotactic radiosurgery for glial neoplasms. Rats were randomized to control or treatment groups after implantation of C6 glioma cells into the right frontal region; 14 days later, 19 rats underwent stereotactic radiosurgical treatment of the induced tumor, using the 4-mm collimator of the gamma unit. Both groups were observed for up to 65 days after implantation. Treated animals had a mean survival of 39.2 days; the 22 control animals lived a mean of 29.4 days before death from tumor growth (P = 0.07). Six treated animals (32%), but only one control animal, survived the full observation period (P = 0.07). The mean tumor diameter in the control group was 9.64 mm; in the radiosurgery group, it was 6.47 mm (P = 0.001). Compared with tumors in control animals, treated tumors had a hypocellular appearance (P less than 0.001) and demonstrated cellular edema (P less than 0.005) under light microscopy, indicating a direct cytotoxic response to treatment. No difference was identified in the amount of tumor necrosis, intratumor hemorrhage, or degree of brain invasion between the two groups. Variations in the maximum treatment dose (30, 40, 50, 70, or 100 Gy) did not result in observed differences in tumor response. This in vivo rat malignant glioma model is a valuable tool to evaluate the tumoricidal effects of single-fraction, focused irradiation. Additional studies are warranted to evaluate dose-response relationships, radiation sensitizers, and use of radiosurgery with other adjuvant treatments.

Patient outcomes after stereotactic radiosurgery for "operable" arteriovenous malformations.

To define the outcomes after stereotactic radiosurgery performed for smaller volume arteriovenous malformations (AVMs) that are potentially suitable for surgical removal, we retrospectively reviewed our 4-year experience in 65 patients who declined microsurgery. All 65 patients had Spetzler-Martin Grade I or II AVMs and a minimum follow-up of 24 months (median, 29 mo). Symptomatic improvement after radiosurgery occurred in 52% of patients with seizures and in 63% of patients with headaches. The annual risk of AVM hemorrhage during the latency interval after radiosurgery was 3.7%. Five patients (7.7%) had a subsequent hemorrhage (all within 8 mo of radiosurgery); two died, and three recovered (one after hematoma evacuation and two with conservative management). Forty-seven patients (72%) returned to their previous employment status or activity level within 1 week of radiosurgery (92% within 1 yr). No patient suffered radiation-related complications. Twenty-seven (84%) of 32 patients evaluated by postradiosurgical angiography had complete AVM obliteration. Radiosurgery is an effective and less invasive management strategy for Grade I or II AVM patients who are either medically unsuitable for or unwilling to undergo surgical removal. The risk of AVM hemorrhage during the latency interval until obliteration occurs appears to be no different than the natural history of untreated AVMs. These results (including hemorrhage prevention and symptom amelioration) indicate that the conservative management of small AVMs can rarely be justified.