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Hideyuki Kano, L. Dade Lunsford, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Nasir R. Awan, Ajay Niranjan, Josef Novotny Jr. and Douglas Kondziolka

Object

The aim of this paper was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I and II arteriovenous malformations (AVMs).

Methods

Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs, including 217 patients with AVMs classified as Spetzler-Martin Grade I or II. The median maximum diameter and target volumes were 1.9 cm (range 0.5–3.8 cm) and 2.3 cm3 (range 0.1–14.1 cm3), respectively. The median margin dose was 22 Gy (range 15–27 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MR imaging in 148 patients and by angiography in 100 patients with a median follow-up of 64 months (range 6–247 months). The actuarial rates of total obliteration determined by angiography or MR imaging after 1 SRS procedure were 58%, 87%, 90%, and 93% at 3, 4, 5, and 10 years, respectively. The median time to complete MR imaging–determined obliteration was 30 months. Factors associated with higher AVM obliteration rates were smaller AVM target volume, smaller maximum diameter, and greater marginal dose. Thirteen patients (6%) suffered hemorrhages during the latency period, and 6 patients died. Cumulative rates of AVM hemorrhage 1, 2, 3, 5, and 10 years after SRS were 3.7%, 4.2%, 4.2%, 5.0%, and 6.1%, respectively. This corresponded to rates of annual bleeding risk of 3.7%, 0.3%, and 0.2% for Years 0–1, 1–5, and 5–10, respectively, after SRS. The presence of a coexisting aneurysm proximal to the AVM correlated with a significantly higher hemorrhage risk. Temporary symptomatic adverse radiation effects developed in 5 patients (2.3%) after SRS, and 2 patients (1%) developed delayed cysts.

Conclusions

Stereotactic radiosurgery is a gradually effective and relatively safe option for patients with smaller volume Spetzler-Martin Grade I or II AVMs who decline initial resection. Hemorrhage after obliteration did not occur in this series. Patients remain at risk for a bleeding event during the latency interval until obliteration occurs. Patients with aneurysms and an AVM warrant more aggressive surgical or endovascular treatment to reduce the risk of a hemorrhage in the latency period after SRS.

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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Nasir R. Awan, Ajay Niranjan, Josef Novotny Jr. and L. Dade Lunsford

Object

The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for pediatric arteriovenous malformations (AVMs).

Methods

Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 135 patients were younger than 18 years of age. The median maximum diameter and target volumes were 2.0 cm (range 0.6–5.2 cm) and 2.5 cm3 (range 0.1–17.5 cm3), respectively. The median margin dose was 20 Gy (range 15–25 Gy).

Results

The actuarial rates of total obliteration documented by angiography or MR imaging at 71.3 months (range 6–264 months) were 45%, 64%, 67%, and 72% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographically documented obliteration was 48.9 months. Of 81 patients with 4 or more years of follow-up, 57 patients (70%) had total obliteration documented by angiography. Factors associated with a higher rate of documented AVM obliteration were smaller AVM target volume, smaller maximum diameter, and larger margin dose. In 8 patients (6%) a hemorrhage occurred during the latency interval, and 1 patient died. The rates of AVM hemorrhage after SRS were 0%, 1.6%, 2.4%, 5.5%, and 10.0% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.8%. Larger volume AVMs were associated with a significantly higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects developed in 2 patients (1.5%) after SRS, and in 1 patient (0.7%) delayed cyst formation occurred.

Conclusions

Stereotactic radiosurgery is a gradually effective and relatively safe management option for pediatric patients in whom surgery is considered to pose excessive risks. Although hemorrhage after AVM obliteration did not occur in the present series, patients remain at risk during the latency interval until obliteration is complete. The best candidates for SRS are pediatric patients with smaller volume AVMs located in critical brain regions.

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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Nasir R. Awan, Ajay Niranjan, Josef Novotny Jr. and L. Dade Lunsford

Object

The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs).

Methods

Between 1987 and 2006, Gamma Knife surgery was performed in 996 patients with AVMs. During this period, repeat SRS was performed in 105 patients who had incompletely obliterated AVMs at a median of 40.9 months after initial SRS (range 27.5–139 months). The median AVM target volume was 6.4 cm3 (range 0.2–26.3 cm3) at initial SRS but was reduced to 2.3 cm3 (range 0.1–18.2 cm3) at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 18 Gy.

Results

The actuarial rate of total obliteration by angiography or MR imaging after repeat SRS was 35%, 68%, 77%, and 80% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographic or MR imaging obliteration after repeat SRS was 39 months. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume (p = 0.038) and a volume reduction of 50% or more after the initial procedure (p = 0.014). Seven patients (7%) had a hemorrhage in the interval between initial SRS and repeat SRS. Seventeen patients (16%) had hemorrhage after repeat SRS and 6 patients died. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.9%, 8.1%, 10.1%, 10.1%, and 22.4% at 1, 2, 3, 5, and 10 years, respectively, which translate to annual hemorrhage rates of 4.05% and 1.79% of patients developing new post–repeat-SRS hemorrhages per year for Years 0–2 and 2–10 following repeat SRS. Factors associated with a higher risk of hemorrhage after repeat SRS were a greater number of prior hemorrhages (p = 0.008), larger AVM target volume at initial SRS (p = 0.010), larger target volume at repeat SRS (p = 0.002), initial AVM volume reduction less than 50% (p = 0.019), and a higher Pollock-Flickinger score (p = 0.010). Symptomatic adverse radiation effects developed in 5 patients (4.8%) after initial SRS and in 10 patients (9.5%) after repeat SRS. Prior embolization (p = 0.022) and a higher Spetzler-Martin grade (p = 0.004) were significantly associated with higher rates of adverse radiation effects after repeat SRS. Delayed cyst formation occurred in 5 patients (4.8%) at a median of 108 months after repeat SRS (range 47–184 months).

Conclusions

Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate. Hemorrhage after obliteration did not occur in this series. The best results for patients with incompletely obliterated AVMs were seen in patients with a smaller residual nidus volume and no prior hemorrhages.

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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Ajay Niranjan, Josef Novotny Jr. and L. Dade Lunsford

Object

The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the basal ganglia and thalamus.

Methods

Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 56 patients had AVMs of the basal ganglia and 77 had AVMs of the thalamus. In this series, 113 (85%) of 133 patients had a prior hemorrhage. The median target volume was 2.7 cm3 (range 0.1–20.7 cm3) and the median margin dose was 20 Gy (range 15–25 Gy).

Results

Obliteration of the AVM eventually was documented on MR imaging in 78 patients and on angiography in 63 patients in a median follow-up period of 61 months (range 2–265 months). The actuarial rates documenting total obliteration after radiosurgery were 57%, 70%, 72%, and 72% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration included AVMs located in the basal ganglia, a smaller target volume, a smaller maximum diameter, and a higher margin dose. Fifteen (11%) of 133 patients suffered a hemorrhage during the latency period and 7 patients died. The rate of post-SRS AVM hemorrhage was 4.5%, 6.2%, 9.0%, 11.2%, and 15.4% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 4.7%. When 5 patients with 7 hemorrhages occurring earlier than 6 months after SRS were removed from this analysis, the annual hemorrhage rate decreased to 2.7%. Larger volume AVMs had a higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 6 patients (4.5%), and in 1 patient a delayed cyst developed 56 months after SRS. No patient died of AREs. Factors associated with a higher risk of symptomatic AREs were larger target volume, larger maximum diameter, lower margin dose, and a higher Pollock-Flickinger score.

Conclusions

Stereotactic radiosurgery is a gradually effective and relatively safe management option for deep-seated AVMs in the basal ganglia and thalamus. Although hemorrhage after obliteration did not occur in the present series, patients remain at risk during the latency interval between SRS and obliteration. The best candidates for SRS are patients with smaller volume AVMs located in the basal ganglia.

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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Ajay Niranjan, Josef Novotny Jr. and L. Dade Lunsford

Object

In this paper, the authors' goal was to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the medulla, pons, and midbrain.

Methods

Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 67 patients had AVMs in the brainstem. In this series, 51 patients (76%) had a prior hemorrhage. The median target volume was 1.4 cm3 (range 0.1–13.4 cm3). The median margin dose was 20 Gy (range 14–25.6 Gy).

Results

Obliteration of the AVMs was eventually documented in 35 patients at a median follow-up of 73 months (range 6–269 months). The actuarial rates of documentation of total obliteration were 41%, 70%, 70%, and 76% at 3, 4, 5, and 10 years, respectively. Higher rates of AVM obliteration were associated only with a higher margin dose. Four patients (6%) suffered a hemorrhage during the latency period, and 2 patients died. The rate of AVM hemorrhage after SRS was 3.0%, 3.0%, and 5.8% at 1, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.9%. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 7 patients (10%) after SRS, and a delayed cyst developed in 2 patients (3%). One patient died at an outside institution with symptoms of AREs and unrecognized hydrocephalus. Higher 12-Gy volumes and higher Spetzler-Martin grades were associated with a higher risk of symptomatic AREs. Ten of 22 patients who had ocular dysfunction before SRS had improvement, 9 were unchanged, and 3 were worse due to AREs. Eight of 14 patients who had hemiparesis before SRS improved, 5 were unchanged, and 1 was worse.

Conclusions

Although hemorrhage after obliteration did not occur in this series, patients remained at risk during the latency interval until obliteration occurred. Thirty-eight percent of the patients who had neurological deficits due to prior hemorrhage improved. Higher dose delivery in association with conformal and highly selective SRS is required for safe and effective radiosurgery.

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Hideyuki Kano, Douglas Kondziolka, John C. Flickinger, Kyung-Jae Park, Phillip V. Parry, Huai-che Yang, Sait Sirin, Ajay Niranjan, Josef Novotny Jr. and L. Dade Lunsford

Object

The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery.

Methods

In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm3. Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8–13.8 months). The median target volume was 11.5 cm3 (range 4.0–26 cm3) in the first-stage SRS and 9.5 cm3 in the second-stage SRS. The median margin dose was 16 Gy (range 13–18 Gy) for both stages.

Results

In 17 patients, AVM obliteration was confirmed after 2–4 SRS procedures at a median follow-up of 87 months (range 0.4–209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33–113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0–1, 1–5, and 5–10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS.

Conclusions

Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

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Huai-che Yang, Hideyuki Kano, Nasir Raza Awan, L. Dade Lunsford, Ajay Niranjan, John C. Flickinger, Josef Novotny Jr., Jagdish P. Bhatnagar and Douglas Kondziolka

Object

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium-sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods

Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results

The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions

Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

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Yoshio Arai, Hideyuki Kano, L. Dade Lunsford, Josef Novotny Jr., Ajay Niranjan, John C. Flickinger and Douglas Kondziolka

Object

The object of this study was to determine whether the radiation dose rate affects clinical outcomes in patients who undergo stereotactic Gamma Knife surgery (GKS) to manage typical trigeminal neuralgia (TN).

Methods

The authors retrospectively studied pain relief in 165 patients with medically intractable TN, who underwent 80-Gy GKS using a single 4-mm collimator between 1994 and 2005. No patient had received prior radiation treatment. The measured relative helmet output factor of the Gamma Knife was 0.8 throughout this interval, and the dose rate varied from 1.21 Gy/minute to 3.74 Gy/minute (median 2.06 Gy/minute). Irradiation time varied from 26.73 to 95.11 minutes. The authors divided patients into a low-dose-rate (LDR) group, in which the dose rate varied from 1.21 to 2.05 Gy/minute, and a high-dose-rate (HDR) group, in which the dose rate varied from 2.06 to 3.74 Gy/minute. Post-GKS, the patients' pain control was determined using the Barrow Neurological Institute (BNI) pain scale.

There was no statistically significant difference between groups with respect to history of prior microvascular decompression (p = 0.410) or peripheral neuroablative procedures (p = 0.583). The length of symptoms in patients varied from 3 to 414 months with a median of 84 months (p = 0.698). Median follow-up was 26 months with a maximum of 139 months.

Results

Initial pain relief was obtained in 71% of patients in the LDR group and 78% in the HDR group (p = 0.547). Patients who initially obtained improved pain relief (BNI Scores I–IIIa) after GKS maintained pain control for median durations of 52 months (LDR group) and 54 months (HDR group) (p = 0.403). New or increased facial sensory dysfunction was found in 14.5% of patients in the LDR group and in 19.3% of patients in the HDR group (p = 0.479).

Conclusions

The authors found that the GKS dose rate did not affect pain control or morbidity within the range of 1.21–3.74 Gy/minute. Cobalt 60 source decay did not affect outcomes of GKS for TN pain management, even for dose rates approximating a 2-half-life decay of the isotope.

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Josef Novotny Jr., Jagdish P. Bhatnagar, Ajay Niranjan, Mubina A. Quader, M. Saiful Huq, Greg Bednarz, John C. Flickinger, Douglas Kondziolka and L. Dade Lunsford

Object

The recently introduced Leksell Gamma Knife (LGK) Perfexion is an entirely new system with a different beam geometry compared with the LGK 4C. The new Perfexion system has 192 cobalt-60 sources that are fixed on 8 sectors (each sector has 24 sources). Each sector can be moved independently of the others and can be set to 1 of 5 different positions: 3 positions defining collimator sizes of 4, 8, and 16 mm; an off position (sources are blocked); and a home position. The purpose of this study is to compare the dosimetric characteristics of the GK 4C and the Perfexion models. This comparison is important especially for the treatment of functional disorders when only a single shot with the 4- or 8-mm collimator is used.

Methods

A 160-mm-diameter spherical polystyrene phantom was used for all measurements and calculations. The irradiation geometry consisted of the placement of a single shot at the center of this phantom. Comparisons were made among different dosimetric parameters obtained from calculations performed using Leksell GammaPlan v. 8.0 and measurements performed using film dosimetry. The dosimetric parameters investigated were dose profiles for all collimators in all 3 stereotactic planes (x, y, and z) including the full width at half maximum and the penumbra for each profile, cumulative dose–volume histograms, the volume encompassed by the 50% isodose surface, the mean doses delivered to a defined matrix volume, and relative output factors for all collimator sizes.

Results

There was excellent agreement between the dosimetric parameters of GK 4C and Perfexion for the 4- and 8-mm collimators.

Conclusions

The results of this study suggest that consistent treatments of functional disorders will be delivered using either GK 4C or Perfexion.