Dale Ding, Chun-Po Yen, Zhiyuan Xu, Robert M. Starke and Jason P. Sheehan
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.
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.
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 cm3 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.
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.
Dale Ding, Chun-Po Yen, Robert M. Starke, Zhiyuan Xu and Jason P. Sheehan
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.
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 cm3 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.
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.
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.
Cheng-Chia Lee, Chun-Po Yen, Zhiyuan Xu, David Schlesinger and Jason Sheehan
The use of radiosurgery has been well accepted for treating small to medium-size metastatic brain tumors (MBTs). However, its utility in treating large MBTs remains uncertain due to potentially unfavorable effects such as progressive perifocal brain edema and neurological deterioration. In this retrospective study the authors evaluated the local tumor control rate and analyzed possible factors affecting tumor and brain edema response.
The authors defined a large brain metastasis as one with a measurement of 3 cm or more in at least one of the 3 cardinal planes (coronal, axial, or sagittal). A consecutive series of 109 patients with 119 large intracranial metastatic lesions were treated with Gamma Knife surgery (GKS) between October 2000 and December 2012; the median tumor volume was 16.8 cm3 (range 6.0–74.8 cm3). The pre-GKS Karnofsky Performance Status (KPS) score for these patients ranged from 70 to 100. The most common tumors of origin were non–small cell lung cancers (29.4% of cases in this series). Thirty-six patients (33.0%) had previously undergone a craniotomy (1–3 times) for tumor resection. Forty-three patients (39.4%) underwent whole-brain radiotherapy (WBRT) before GKS. Patients were treated with GKS and followed clinically and radiographically at 2- to 3-month intervals thereafter.
The median duration of imaging follow-up after GKS for patients with large MBTs in this series was 6.3 months. In the first follow-up MRI studies (performed within 3 months after GKS), 77 lesions (64.7%) had regressed, 24 (20.2%) were stable, and 18 (15.1%) were found to have grown. Peritumoral brain edema as defined on T2-weighted MRI sequences had decreased in 79 lesions (66.4%), was stable in 21 (17.6%), but had progressed in 19 (16.0%). In the group of patients who survived longer than 6 months (76 patients with 77 MBTs), 88.3% of the MBTs (68 of 77 lesions) had regressed or remained stable at the most recent imaging follow-up, and 89.6% (69 of 77 lesions) showed regression of perifocal brain edema volume or stable condition. The median duration of survival after GKS was 8.3 months for patients with large MBTs. Patients with small cell lung cancer and no previous WBRT had a significantly higher tumor control rate as well as better brain edema relief. Patients with a single metastasis, better KPS scores, and no previous radiosurgery or WBRT were more likely to decrease corticosteroid use after GKS. On the other hand, higher pre-GKS KPS score was the only factor that showed a statistically significant association with longer survival.
Treating large MBTs using either microsurgery or radiosurgery is a challenge for neurosurgeons. In selected patients with large brain metastases, radiosurgery offered a reasonable local tumor control rate and favorable functional preservation. Exacerbation of underlying edema was rare in this case series. Far more commonly, edema and steroid use were lessened after radiosurgery. Radiosurgery appears to be a reasonable option for some patients with large MBTs.
David Schlesinger, Zhiyuan Xu, Frances Taylor, Chun-Po Yen and Jason Sheehan
The Extend system for the Gamma Knife Perfexion makes possible multifractional Gamma Knife treatments. The Extend system consists of a vacuum-monitored immobilization frame and a positioning measurement system used to determine the location of the patient's head within the frame at the time of simulation imaging and before each treatment fraction. The measurement system consists of a repositioning check tool (RCT), which attaches to the Extend frame, and associated digital measuring gauges. The purpose of this study is to evaluate the performance of the Extend system for patient repositioning before each treatment session (fraction) and patient immobilization between (interfraction) and during (intrafraction) each session in the first 10 patients (36 fractional treatments) treated at the University of Virginia.
The RCT was used to acquire a set of reference measurements for each patient position at the time of CT simulation. Repositioning measurements were acquired before each fraction, and the patient position was adjusted until the residual radial difference from the reference position measurements was less than 1 mm. After treatment, patient position measurements were acquired, and the difference between those measurements and the ones obtained for patient position before the fraction was calculated as a measure of immobilization capability.
Analysis of patient setup and immobilization performance included calculation of the group mean, standard deviation (SD), and distribution of systematic (components affecting all fractions) and random (per fraction) uncertainty components.
Across all patients and fractions, the mean radial setup difference from the reference measurements was 0.64 mm, with an SD of 0.24 mm. The distribution of systematic uncertainty (Σ) was 0.17 mm, and the distribution of random uncertainty (σ) was 0.16 mm. The root mean square (RMS) differences for each plate of the RCT were as follows: right = 0.35 mm; left = 0.41 mm; superior = 0.28 mm; and anterior = 0.20 mm.
The mean intrafractional positional difference across all treatments was 0.47 mm, with an SD of 0.30 mm. The distribution of systematic uncertainty was 0.18 mm, and the distribution of random uncertainty was 0.22 mm. The RMS differences for each plate of the RCT were 0.24 mm for the right plate, 0.22 mm for the left plate, 0.24 mm for the superior plate, and 0.34 mm for the anterior plate. Data from 1 fraction were excluded from the analysis because the vacuum-monitoring interlock detected patient motion, which in turn required repositioning in the middle of the fraction.
The Extend system can be used to reposition and immobilize patients in a radiosurgical setting. However, care should be taken to acquire measurements that can implicitly account for rotations of the patient's head. Further work is required to determine the sensitivity of the vacuum interlock to detect patient motion.
Chun-Po Yen, Joshua M. Beckman, Andrew C. Vivas, Konrad Bach and Juan S. Uribe
The authors investigated whether the presence of intradiscal vacuum phenomenon (IVP) results in greater correction of disc height and restoration of segmental lordosis (SL).
A retrospective chart review was performed on every patient at the University of South Florida's Department of Neurosurgery treated with lateral lumbar interbody fusion between 2011 and 2015. From these charts, preoperative plain radiographs and CT images were reviewed for the presence of IVP. Preoperative and postoperative posterior disc height (PDH), anterior disc height (ADH), and SL were measured at disc levels with IVP and compared with those at disc levels without IVP using the t-test. Linear regression was used to evaluate the factors that predict changes in PDH, ADH, and SL.
One hundred forty patients with 247 disc levels between L-1 and L-5 were treated with lateral lumbar interbody fusion. Among all disc levels treated, the mean PDH increased from 3.69 to 6.66 mm (p = 0.011), the mean ADH increased from 5.45 to 11.53 mm (p < 0.001), and the mean SL increased from 9.59° to 14.55° (p < 0.001). Significantly increased PDH was associated with the presence of IVP, addition of pedicle screws, and lack of cage subsidence; significantly increased ADH was associated with the presence of IVP, anterior longitudinal ligament (ALL) release, addition of pedicle screws, and lack of subsidence; and significantly increased SL was associated with the presence of IVP and ALL release.
IVP in patients with degenerative spinal disease remains grossly underreported. The data from the present study suggest that the presence of IVP results in increased restoration of disc height and SL.
Mohamed Samy Elhammady and Roberto C. Heros
Chun-Po Yen, Dale Ding, Ching-Hsiao Cheng, Robert M. Starke, Mark Shaffrey and Jason Sheehan
A relatively benign natural course of unruptured cerebral arteriovenous malformations (AVMs) has recently been recognized, and the decision to treat incidentally found AVMs has been questioned. This study aims to evaluate the long-term imaging and clinical outcomes of patients with asymptomatic, incidentally discovered AVMs treated with Gamma Knife surgery (GKS).
Thirty-one patients, each with an incidentally diagnosed AVM, underwent GKS between 1989 and 2009. The nidus volumes ranged from 0.3 to 11.1 cm3 (median 3.2 cm3). A margin dose between 15 and 26 Gy (median 20 Gy) was used to treat the AVMs. Four patients underwent repeat GKS for still-patent AVM residuals after the initial GKS procedure. Clinical follow-up ranged from 24 to 196 months, with a mean of 78 months (median 51 months) after the initial GKS.
Following GKS, 19 patients (61.3%) had a total AVM obliteration on angiography. In 7 patients (22.6%), no flow voids were observed on MRI but angiographic confirmation was not available. In 5 patients (16.1%), the AVMs remained patent. A small nidus volume was significantly associated with increased AVM obliteration rate. Thirteen patients (41.9%) developed radiation-induced imaging changes: 11 were asymptomatic (35.5%), 1 had only headache (3.2%), and 1 developed seizure and neurological deficits (3.2%). Two patients each had 1 hemorrhage during the latency period (116.5 risk years), yielding an annual hemorrhage rate of 1.7% before AVM obliteration.
The decision to treat asymptomatic AVMs, and if so, which treatment approach to use, remain the subject of debate. GKS as a minimally invasive procedure appears to achieve a reasonable outcome with low procedure-related morbidity. In those patients with incidental AVMs, the benefits as well as the risks of radiosurgical intervention will only be fully defined with long-term follow-up.
Dale Ding, Mark Quigg, Robert M. Starke, Zhiyuan Xu, Chun-Po Yen, Colin J. Przybylowski, Blair K. Dodson and Jason P. Sheehan
The temporal lobe is particularly susceptible to epileptogenesis. However, the routine use of anticonvulsant therapy is not implemented in temporal lobe AVM patients without seizures at presentation. The goals of this case-control study were to determine the radiosurgical outcomes for temporal lobe AVMs and to define the effect of temporal lobe location on postradiosurgery AVM seizure outcomes.
From a database of approximately 1400 patients, the authors generated a case cohort from patients with temporal lobe AVMs with at least 2 years follow-up or obliteration. A control cohort with similar baseline AVM characteristics was generated, blinded to outcome, from patients with non-temporal, cortical AVMs. They evaluated the rates and predictors of seizure freedom or decreased seizure frequency in patients with seizures or de novo seizures in those without seizures.
A total of 175 temporal lobe AVMs were identified based on the inclusion criteria. Seizure was the presenting symptom in 38% of patients. The median AVM volume was 3.3 cm3, and the Spetzler-Martin grade was III or higher in 39% of cases. The median radiosurgical prescription dose was 22 Gy. At a median clinical follow-up of 73 months, the rates of seizure control and de novo seizures were 62% and 2%, respectively. Prior embolization (p = 0.023) and lower radiosurgical dose (p = 0.027) were significant predictors of seizure control. Neither temporal lobe location (p = 0.187) nor obliteration (p = 0.522) affected seizure outcomes. The cumulative obliteration rate was 63%, which was significantly higher in patients without seizures at presentation (p = 0.046). The rates of symptomatic and permanent radiation-induced changes were 3% and 1%, respectively. The annual risk of postradiosurgery hemorrhage was 1.3%.
Radiosurgery is an effective treatment for temporal lobe AVMs. Furthermore, radiosurgery is protective against seizure progression in patients with temporal lobe AVM–associated seizures. Temporal lobe location does not affect radiosurgery-induced seizure control. The low risk of new-onset seizures in patients with temporal or extratemporal AVMs does not seem to warrant prophylactic use of anticonvulsants.