Chun-Po Yen

A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients.

OBJECT The authors performed a study to review outcomes following Gamma Knife radiosurgery for cerebral arteriovenous malformations (AVMs) and to create a practical scale to predict long-term outcome. METHODS Outcomes were reviewed in 1012 patients who were followed up for more than 2 years. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent, symptomatic, radiation-induced complication. Preradiosurgery patient and AVM characteristics predictive of outcome in multivariate analysis were weighted according to their odds ratios to create the Virginia Radiosurgery AVM Scale. RESULTS The mean follow-up time was 8 years (range 2-20 years). Arteriovenous malformation obliteration occurred in 69% of patients. Postradiosurgery hemorrhage occurred in 88 patients, for a yearly incidence of 1.14%. Radiation-induced changes occurred in 387 patients (38.2%), symptoms in 100 (9.9%), and permanent deficits in 21 (2.1%). Favorable outcome was achieved in 649 patients (64.1%). The Virginia Radiosurgery AVM Scale was created such that patients were assigned 1 point each for having an AVM volume of 2-4 cm(3), eloquent AVM location, or a history of hemorrhage, and 2 points for having an AVM volume greater than 4 cm(3). Eighty percent of patients who had a score of 0-1 points had a favorable outcome, as did 70% who had a score of 2 points and 45% who had a score of 3-4 points. The Virginia Radiosurgery AVM Scale was still predictive of outcome after controlling for predictive Gamma Knife radiosurgery treatment parameters, including peripheral dose and number of isocenters, in a multivariate analysis. The Spetzler-Martin grading scale and the Radiosurgery-Based Grading Scale predicted favorable outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. CONCLUSIONS Gamma Knife radiosurgery can be used to achieve long-term AVM obliteration and neurological preservation in a predictable fashion based on patient and AVM characteristics.

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases.

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

High-intensity focused ultrasound surgery of the brain: part 1--A historical perspective with modern applications.

THE FIELD OF magnetic resonance imaging-guided high-intensity focused ultrasound surgery (MRgFUS) is a rapidly evolving one, with many potential applications in neurosurgery. The first of 3 articles on MRgFUS, this article focuses on the historical development of the technology and its potential applications in modern neurosurgery. The evolution of MRgFUS has occurred in parallel with modern neurological surgery, and the 2 seemingly distinct disciplines share many of the same pioneering figures. Early studies on focused ultrasound treatment in the 1940s and 1950s demonstrated the ability to perform precise lesioning in the human brain, with a favorable risk-benefit profile. However, the need for a craniotomy, as well as the lack of sophisticated imaging technology, resulted in limited growth of high-intensity focused ultrasound for neurosurgery. More recently, technological advances have permitted the combination of high-intensity focused ultrasound along with magnetic resonance imaging guidance to provide an opportunity to effectively treat a variety of central nervous system disorders. Although challenges remain, high-intensity focused ultrasound-mediated neurosurgery may offer the ability to target and treat central nervous system conditions that were previously extremely difficult to address. The remaining 2 articles in this series will focus on the physical principles of modern MRgFUS as well as current and future avenues for investigation.

Stereotactic radiosurgery for pituitary adenomas: a comprehensive review of indications, techniques and long-term results using the Gamma Knife

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

Radiosurgery for ruptured intracranial arteriovenous malformations

OBJECT Ruptured intracranial arteriovenous malformations (AVMs) are at a significantly greater risk for future hemorrhage than unruptured lesions, thereby necessitating treatment in the majority of cases. In a retrospective, single-center study, the authors describe the outcomes after radiosurgery in a large cohort of patients with ruptured AVMs. METHODS From an institutional review board-approved, prospectively collected AVM radiosurgery database, the authors identified all patients with a history of AVM rupture. They analyzed obliteration rates in all patients in whom radiological follow-up data were available (n = 639). However, to account for the latency period associated with radiosurgery, only those patients with more than 2 years of radiological follow-up and those with earlier AMV obliteration were included in the analysis of prognostic factors related to obliteration and complications. This resulted in a cohort of 565 patients with ruptured AVMs for whom data were analyzed; these patients had a median radiological follow-up of 57 months and a median age of 29 years. Twenty-one percent of the patients underwent preradiosurgery embolization. The median volume and prescription dose were 2.1 cm(3) and 22 Gy, respectively. The Spetzler-Martin grade was III or higher in 56% of patients, the median radiosurgery-based AVM score was 1.08, and the Virginia Radiosurgery AVM Scale (RAS) score was 3 to 4 points in 44%. Survival and regression analyses were performed to determine obliteration rates over time and predictors of obliteration and complications. RESULTS In the overall population of 639 patients with ruptured AVMs, the obliteration rate was 11.1% based on MRI only (71 of 639 patients), 56.0% based on angiography (358 of 639), and 67.1% based on combined modalities (429 of 639 patients). In the cohort of patients with 2 years of follow-up or an earlier AVM obliteration, the cumulative obliteration rate was 76% and the actuarial obliteration rates were 41% and 64% at 3 and 5 years, respectively. Multivariate analysis identified the absence of preradiosurgery embolization (p < 0.001), increased prescription dose (p = 0.001), the presence of a single draining vein (p = 0.046), no postradiosurgery-related hemorrhage (p = 0.007), and lower Virginia RAS score (p = 0.020) as independent predictors of obliteration. The annual risk of a hemorrhage occurring during the latency period was 2.0% and the rate of hemorrhage-related morbidity and mortality was 1.6%. Multivariate analysis showed that decreased prescription dose (p < 0.001) and multiple draining veins (p = 0.003) were independent predictors of postradiosurgery hemorrhage. The rates of symptomatic and permanent radiation-induced changes were 8% and 2.7%, respectively. In the multivariate analysis, a single draining vein (p < 0.001) and higher Virginia RAS score (p = 0.005) were independent predictors of radiation-induced changes following radiosurgery. CONCLUSIONS Radiosurgery effectively treats ruptured AVMs with an acceptably low risk-to-benefit ratio. For patients with ruptured AVMs, favorable outcomes are more likely when preradiosurgical embolization is avoided and a higher prescription dose can be delivered.

Radiosurgery for low-grade intracranial arteriovenous malformations

OBJECT Low-grade, or Spetzler-Martin (SM) Grades I and II, arteriovenous malformations (AVMs) are associated with lower surgical morbidity rates than higher-grade lesions. While radiosurgery is now widely accepted as an effective treatment approach for AVMs, the risks and benefits of the procedure for low-grade AVMs, as compared with microsurgery, remain poorly understood. The authors of this study present the outcomes for a large cohort of low-grade AVMs treated with radiosurgery. METHODS From an institutional radiosurgery database comprising approximately 1450 AVM cases, all patients with SM Grade I and II lesions were identified. Patients with less than 2 years of radiological follow-up, except those with complete AVM obliteration, were excluded from analysis. Univariate and multivariate Cox proportional-hazards and logistic regression analyses were used to determine factors associated with obliteration, radiation-induced changes (RICs), and hemorrhage following radiosurgery. RESULTS Five hundred two patients harboring low-grade AVMs were eligible for analysis. The median age was 35 years, 50% of patients were male, and the most common presentation was hemorrhage (47%). The median AVM volume and prescription dose were 2.4 cm(3) and 23 Gy, respectively. The median radiological and clinical follow-up intervals were 48 and 62 months, respectively. The cumulative obliteration rate was 76%. The median time to obliteration was 40 months, and the actuarial obliteration rates were 66% and 80% at 5 and 10 years, respectively. Independent predictors of obliteration were no preradiosurgery embolization (p < 0.001), decreased AVM volume (p = 0.005), single draining vein (p = 0.013), lower radiosurgery-based AVM scale score (p = 0.016), and lower Virginia Radiosurgery AVM Scale (Virginia RAS) score (p = 0.001). The annual postradiosurgery hemorrhage rate was 1.4% with increased AVM volume (p = 0.034) and lower prescription dose (p = 0.006) as independent predictors. Symptomatic and permanent RICs were observed in 8.2% and 1.4% of patients, respectively. No preradiosurgery hemorrhage (p = 0.011), a decreased prescription dose (p = 0.038), and a higher Virginia RAS score (p = 0.001) were independently associated with postradiosurgery RICs. CONCLUSIONS Spetzler-Martin Grade I and II AVMs are very amenable to successful treatment with stereotactic radiosurgery. While patient, physician, and institutional preferences frequently dictate the final course of treatment, radiosurgery offers a favorable risk-to-benefit profile for the management of low-grade AVMs.

Radiosurgery for Spetzler-Martin Grade III arteriovenous malformations.

OBJECT Intracranial arteriovenous malformations (AVMs) are most commonly classified based on their Spetzler-Martin grades. Due to the composition of the Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous, comprising 4 distinct lesion subtypes. The management of this class of AVMs and the optimal treatment approach when intervention is indicated remain controversial. The authors report their experience with radiosurgery for the treatment of Grade III AVMs in a large cohort of patients. METHODS All patients with Spetzler-Martin Grade III AVMs treated with radiosurgery at the University of Virginia over the 20-year span from 1989 to 2009 were identified. Patients who had less than 2 years of radiological follow-up and did not have evidence of complete obliteration during that period were excluded from the study, leaving 398 cases for analysis. The median patient age at treatment was 31 years. The most common presenting symptoms were hemorrhage (59%), seizure (20%), and headache (10%). The median AVM volume was 2.8 cm(3), and the median prescription dose was 20 Gy. The median radiological and clinical follow-up intervals were 54 and 68 months, respectively. Univariate and multivariate Cox proportional hazards and logistic regression analysis were used to identify factors associated with obliteration, postradiosurgery radiation-induced changes (RIC), and favorable outcome. RESULTS Complete AVM obliteration was observed in 69% of Grade III AVM cases at a median time of 46 months after radiosurgery. The actuarial obliteration rates at 3 and 5 years were 38% and 60%, respectively. The obliteration rate was higher in ruptured AVMs than in unruptured ones (p < 0.001). Additionally, the obliteration rate for Grade III AVMs with small size (< 3 cm diameter), deep venous drainage, and location in eloquent cortex was higher than for the other subtypes (p < 0.001). Preradiosurgery AVM rupture (p = 0.016), no preradiosurgery embolization (p = 0.003), increased prescription dose (p < 0.001), fewer isocenters (p = 0.006), and a single draining vein (p = 0.018) were independent predictors of obliteration. The annual risk of postradiosurgery hemorrhage during the latency period was 1.7%. Two patients (0.5%) died of hemorrhage during the radiosurgical latency period. The rates of symptomatic and permanent RIC were 12% and 4%, respectively. Absence of preradiosurgery AVM rupture (p < 0.001) and presence of a single draining vein (p < 0.001) were independent predictors of RIC. Favorable outcome was observed in 63% of patients. Independent predictors of favorable outcome were no preradiosurgery hemorrhage (p = 0.014), increased prescription dose (p < 0.001), fewer isocenters (p = 0.014), deep location (p = 0.014), single draining vein (p = 0.001), and lower Virginia radiosurgery AVM scale score (p = 0.016). CONCLUSIONS Radiosurgery for Spetzler-Martin Grade III AVMs yields relatively high rates of obliteration with a low rate of adverse procedural events. Small and ruptured lesions are more likely to become obliterated after radiosurgery than large and unruptured ones.

Volume-staged versus dose-staged radiosurgery outcomes for large intracranial arteriovenous malformations

OBJECT The aim in this paper was to compare the outcomes of dose-staged and volume-staged stereotactic radio-surgery (SRS) in the treatment of large (> 10 cm(3)) arteriovenous malformations (AVMs). METHODS A systematic literature review was performed using PubMed. Studies written in the English language with at least 5 patients harboring large (> 10 cm(3)) AVMs treated with dose- or volume-staged SRS that reported post-treatment outcomes data were selected for review. Demographic information, radiosurgical treatment parameters, and post-SRS outcomes and complications were analyzed for each of these studies. RESULTS The mean complete obliteration rates for the dose- and volume-staged groups were 22.8% and 47.5%, respectively. Complete obliteration was demonstrated in 30 of 161 (18.6%) and 59 of 120 (49.2%) patients in the dose- and volume-staged groups, respectively. The mean rates of symptomatic radiation-induced changes were 13.5% and 13.6% in dose- and volume-staged groups, respectively. The mean rates of cumulative post-SRS latency period hemorrhage were 12.3% and 17.8% in the dose- and volume-staged groups, respectively. The mean rates of post-SRS mortality were 3.2% and 4.6% in dose- and volume-staged groups, respectively. CONCLUSIONS Volume-staged SRS affords higher obliteration rates and similar complication rates compared with dose-staged SRS. Thus, volume-staged SRS may be a superior approach for large AVMs that are not amenable to single-session SRS. Staged radiosurgery should be considered as an efficacious component of multimodality AVM management.

Radiosurgery for primary motor and sensory cortex arteriovenous malformations: outcomes and the effect of eloquent location.

BACKGROUND Eloquent intracranial arteriovenous malformations (AVMs) located in the primary motor or somatosensory cortex (PMSC) carry a high risk of microsurgical morbidity. OBJECTIVE To evaluate the outcomes of radiosurgery on PMSC AVMs and compare them with radiosurgery outcomes in a matched cohort of noneloquent lobar AVMs. METHODS Between 1989 and 2009, 134 patients with PMSC AVMs underwent Gamma Knife radiosurgery with a median radiographic and clinical follow-up of 64 and 80 months, respectively. Seizure (40.3%) and hemorrhage (28.4%) were the most common presenting symptoms. Pre-radiosurgery embolization was performed in 33.6% of AVMs. Median AVM volume was 4.1 mL (range, 0.1-22.6 mL), and prescription dose was 20 Gy (range, 7-30 Gy). Cox regression analysis was performed to identify factors associated with obliteration. RESULTS The overall obliteration rate, including magnetic resonance imaging and angiography, after radiosurgery was 63%. Obliteration was achieved in 80% of AVMs with a volume less than 3 mL compared with 55% for AVMs larger than 3 mL. No previous embolization (P = .002) and a single draining vein (P = .001) were independent predictors of obliteration on multivariate analysis. The annual post-radiosurgery hemorrhage risk was 2.5%. Radiosurgery-related morbidity was temporary and permanent in 14% and 6% of patients, respectively. Comparing PMSC AVMs with matched noneloquent lobar AVMs, the obliteration rates and clinical outcomes after radiosurgery were not statistically different. CONCLUSION For patients harboring PMSC AVMs, radiosurgery offers a reasonable chance of obliteration with a relatively low complication rate. Eloquent location does not appear to confer the same negative prognostic value for radiosurgery that it does for microsurgery.

Outcomes following single-session radiosurgery for high-grade intracranial arteriovenous malformations.

Abstract Introduction. The management of Spetzler–Martin Grade-IV and -V arteriovenous malformations (AVMs) is controversial due to their uncertain natural history, the high rate of morbidity and mortality associated with microsurgical resection, and the relatively low rate of successful obliteration from less invasive approaches such as radiosurgery and embolization. We present our radiosurgical results for high-grade AVMs. Methods. We identified all patients with Spetzler–Martin Grade-IV and -V AVMs treated with single-session radiosurgery at the University of Virginia between 1989 and 2009. Patients with less than 2 years of follow-up without obliteration were excluded. This yielded 110 patients with a median age 27.6 years. The median AVM volume was 5.7 cc and prescription dose was 19 Gy. The median radiographic and clinical follow-up intervals were 88 and 97 months, respectively. Results. Complete AVM obliteration was identified on MRI only in 11 patients (10%) and confirmed by DSA in 38 patients (34%) for a cumulative obliteration rate of 44%. The actuarial rates of obliteration at 3 and 5 years were 10% and 23%, respectively. The mean and median times to obliteration were 60 months and 43 months, respectively. Significant independent predictors of obliteration were no pre-radiosurgery embolization (P = 0.008), superficial location (P = 0.001), and higher prescription dose (P = 0.028). The annual rate of post-radiosurgery hemorrhage was 3.0%, and symptomatic RIC was observed in 12% of patients. Unruptured AVMs were more likely to have RIC (P = 0.005). The rates of temporary and permanent post-radiosurgery clinical deterioration were 9% and 10%, respectively. Conclusion. Single-session radiosurgery is an acceptable treatment option for select patients harboring high-grade AVMs for which microsurgery or conservative management are associated with an unacceptably high risk of adverse outcomes.