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Greg Bowden, Hideyuki Kano, Huai-che Yang, Ajay Niranjan, John Flickinger and L. Dade Lunsford

Object

The outcomes of stereotactic radiosurgery for arteriovenous malformations (AVMs) within or adjacent to the ventricular system are largely unknown. This study assessed the long-term outcomes and hemorrhage risks for patients with AVMs within this region who underwent Gamma Knife surgery (GKS) at the University of Pittsburgh.

Methods

The authors retrospectively identified 188 patients with ventricular-region AVMs who underwent a single-stage GKS procedure during a 22-year interval. The median patient age was 32 years (range 3–80 years), the median target volume was 4.6 cm3 (range 0.1–22 cm3), and the median marginal dose was 20 Gy (range 13–27 Gy).

Results

Arteriovenous malformation obliteration was confirmed by MRI or angiography in 89 patients during a median follow-up of 65 months (range 2–265 months). The actuarial rates of total obliteration were 32% at 3 years, 55% at 4 years, 60% at 5 years, and 64% at 10 years. Higher rates of AVM obliteration were obtained in the 26 patients with intraventricular AVMs. Twenty-five patients (13%) sustained a hemorrhage during the initial latency interval after GKS, indicating an annual hemorrhage rate of 3.4% prior to AVM obliteration. No patient experienced a hemorrhage after AVM obliteration was confirmed by imaging. Permanent neurological deficits due to adverse radiation effects developed in 7 patients (4%).

Conclusions

Although patients in this study demonstrated an elevated hemorrhage risk that remained until complete obliteration, GKS still proved to be a generally safe and effective treatment for patients with these high-risk intraventricular and periventriclar AVMs.

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Yi-Chieh Hung, Cheng-Chia Lee, Kang-Du Liu, Wen-Yuh Chung, David Hung-Chi Pan and Huai-Che Yang

Object

The authors evaluated individual anatomical variations in the trigeminal nerves of patients with medically intractable trigeminal neuralgia and clarified the relationships among the variations, radiosurgical target locations, and the clinical outcomes after high-dose Gamma Knife surgery (GKS).

Methods

From 2006 through 2011, the authors conducted a retrospective review of 106 cases of primary or secondary trigeminal neuralgia consecutively treated with GKS targeting the dorsal root entry zone (DREZ) for which a maximal dose of 90 Gy and a 20% isodose line to the brainstem were used. A questionnaire was used to evaluate patients' pre- and post-GKS clinical conditions. To evaluate individual anatomical variations among trigeminal nerves, the authors used 3 parameters: the length of the trigeminal nerve in the cistern (nerve length), the length of the target between the radiation shot and the brainstem (targeting length), and the ratio between nerve length and targeting length (targeting ratio).

Results

The median length of the trigeminal nerves in the 106 patients was 9.6 mm (range 6.04−20.74 mm), the median targeting length was 3.8 mm (range 1.81−10.84 mm), and the median targeting ratio was 38% (range 13%− 80%). No statistically significant differences in pain relief and pain recurrence were detected among patients with these various nerve characteristics. However, radiation-induced facial hypesthesia correlated with nerve length and targeting ratio (p < 0.05) but not with absolute distance from the brainstem (targeting length).

Conclusions

In trigeminal neuralgia patients who received DREZ-targeted GKS, the rate of pain relief did not differ according to anatomical nerve variations. However, the frequency of facial hypesthesia was higher among patients in whom the nerve was longer (> 11 mm) or the targeting ratio was lower (< 36%). Adjusting the target according to the targeting ratio, especially for patients with longer nerves, can reduce facial hypesthesia and enable maintenance of effective pain control.

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Hideyuki Kano, John C. Flickinger, Huai-che Yang, Thomas J. Flannery, Daniel Tonetti, Ajay Niranjan and L. Dade Lunsford

Object

The purpose of this study was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs).

Methods

Between 1987 and 2009, SRS was performed in 474 patients with SM Grade III AVMs. The AVMs were categorized by scoring the size (S), drainage (D), and location (L): IIIa was a small AVM (S1D1L1, N = 282); IIIb was a medium/deep AVM (S2D1L0, N = 44); and IIIc was a medium/eloquent AVM (S2D0L1, N = 148). The median target volume was 3.8 ml (range 0.1–26.3 ml) and the margin dose was 20 Gy (range 13–25 Gy). Eighty-one patients (17%) underwent prior embolization, and 58 (12%) underwent prior resection.

Results

At a mean follow-up of 89 months, the total obliteration rates documented by angiography or MRI for all SM Grade III AVMs increased from 48% at 3 years to 69% at 4 years, 72% at 5 years, and 77% at 10 years. The SM Grade IIIa AVMs were more likely to obliterate than other subgroups. The cumulative rate of hemorrhage was 2.3% at 1 year, 4.4% at 2 years, 5.5% at 3 years, 6.4% at 5 years, and 9% at 10 years. The SM Grade IIIb AVMs had a significantly higher cumulative rate of hemorrhage. Symptomatic adverse radiation effects were detected in 6%.

Conclusions

Treatment with SRS was an effective and relatively safe management option for SM Grade III AVMs. Although patients with residual AVMs remained at risk for hemorrhage during the latency interval, the cumulative 10-year 9% hemorrhage risk in this series may represent a significant reduction compared with the expected natural history.

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Hideyuki Kano, Huai-che Yang, Douglas Kondziolka, Ajay Niranjan, Yoshio Arai, John C. Flickinger and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in patients with recurrent or residual intracranial ependymomas after resection and fractionated radiation therapy (RT), the authors assessed overall survival, distant tumor relapse, progression-free survival (PFS), and complications.

Methods

The authors retrospectively reviewed the records of 21 children with ependymomas who underwent SRS for 32 tumors. There were 17 boys and 4 girls with a median age of 6.9 years (range 2.9–17.2 years) in the patient population. All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases was confirmed) RT. Eleven patients had adjuvant chemotherapy. Twelve patients had low-grade ependymomas (17 tumors), and 9 patients had anaplastic ependymomas (15 tumors). The median radiosurgical target volume was 2.2 cm3 (range 0.1–21.4 cm3), and the median dose to the tumor margin was 15 Gy (range 9–22 Gy).

Results

Follow-up imaging demonstrated therapeutic control in 23 (72%) of 32 tumors at a mean follow-up period of 27.6 months (range 6.1–72.8 months). Progression-free survival after the initial SRS was 78.4%, 55.5%, and 41.6% at 1, 2, and 3 years, respectively. Factors associated with a longer PFS included patients without spinal metastases (p = 0.033) and tumor volumes < 2.2 cm3 (median tumor volume 2.2 cm3, p = 0.029). An interval ≥18 months between RT and SRS was also associated with longer survival (p = 0.035). The distant tumor relapse rate despite RT and SRS was 33.6%, 41.0%, and 80.3% at 1, 2, and 3 years, respectively. Factors associated with a higher rate of distant tumor relapse included patients who had spinal metastases before RT (p = 0.037), a fourth ventricle tumor location (p = 0.002), and an RT to SRS interval < 18 months (p = 0.015). The median survival after SRS was 27.6 months (95% CI 19.33–35.87 months). Overall survival after SRS was 85.2%, 53.2%, and 23.0% at 1, 2, and 3 years, respectively. Adverse radiation effects developed in 2 patients (9.5%).

Conclusions

Stereotactic radiosurgery offers an additional option beyond repeat surgery or RT in pediatric patients with residual or recurrent ependymomas after initial management. Patients with smaller-volume tumors and a later recurrence responded best to radiosurgery.

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Cheng-Chia Lee, David Hung-Chi Pan, Wen-Yuh Chung, Kang-Du Liu, Huai-Che Yang, Hsiu-Mei Wu, Wan-Yuo Guo and Yang-Hsin Shih

Object

The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention.

Methods

Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance.

Results

The mean size of the CMs at the time of GKS was 3.2 cm3 (range 0.1–14.6 cm3). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0–150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group.

Conclusions

Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

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Chih-Chun Wu, Wan-Yuo Guo, Wen-Yuh Chung, Hisu-Mei Wu, Chung-Jung Lin, Cheng-Chia Lee, Kang-Du Liu and Huai-che Yang

OBJECTIVE

Gamma Knife surgery (GKS) is a promising treatment modality for patients with vestibular schwannomas (VSs), but a small percentage of patients have persistent postradiosurgical tumor growth. The aim of this study was to determine the clinical and quantitative MRI features of VS as predictors of long-term tumor control after GKS.

METHODS

The authors performed a retrospective study of all patients with VS treated with GKS using the Leksell Gamma Knife Unit between 2005 and 2013 at their institution. A total of 187 patients who had a minimum of 24 months of clinical and radiological assessment after radiosurgery were included in this study. Those who underwent a craniotomy with tumor removal before and after GKS were excluded. Study patients comprised 85 (45.5%) males and 102 (54.5%) females, with a median age of 52.2 years (range 20.4–82.3 years). Tumor volumes, enhancing patterns, and apparent diffusion coefficient (ADC) values were measured by region of interest (ROI) analysis of the whole tumor by serial MRI before and after GKS.

RESULTS

The median follow-up period was 60.8 months (range 24–128.9 months), and the median treated tumor volume was 3.54 cm3 (0.1–16.2 cm3). At last follow-up, imaging studies indicated that 150 tumors (80.2%) showed decreased tumor volume, 20 (10.7%) had stabilized, and 17 (9.1%) continued to grow following radiosurgery. The postradiosurgical outcome was not significantly correlated with pretreatment volumes or postradiosurgical enhancing patterns. Tumors that showed regression within the initial 12 months following radiosurgery were more likely to have a larger volume reduction ratio at last follow-up than those that did not (volume reduction ratio 55% vs 23.6%, respectively; p < 0.001). Compared with solid VSs, cystic VSs were more likely to regress or stabilize in the initial postradiosurgical 6–12-month period and during extended follow-up. Cystic VSs exhibited a greater volume reduction ratio at last follow-up (cystic vs solid: 67.6% ± 24.1% vs 31.8% ± 51.9%; p < 0.001). The mean preradiosurgical maximum ADC (ADCmax) values of all VSs were significantly higher for those with tumor regression or stabilization at last follow-up compared with those with progression (2.391 vs 1.826 × 10−3 mm2/sec; p = 0.010).

CONCLUSIONS

Loss of central enhancement after radiosurgery was a common phenomenon, but it did not correlate with tumor volume outcome. Preradiosurgical MRI features including cystic components and ADCmax values can be helpful as predictors of treatment outcome.

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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 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.