Cheng-Chia Lee and David Hung-Chi Pan
Da Li and Jun-Ting Zhang
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.
Or Cohen-Inbar, Cheng-Chia Lee, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan
The authors review outcomes following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs) and their correlation to postradiosurgery adverse radiation effects (AREs).
From a prospective institutional review board–approved database, the authors identified patients with a minimum of 2 years of follow-up and thin-slice T2-weighted MRI sequences for volumetric analysis. A total of 105 AVM patients were included. The authors analyzed the incidence and quantitative changes in AREs as a function of time after GKRS. Statistical analysis was performed to identify factors related to ARE development and changes in the ARE index.
The median clinical follow-up was 53.8 months (range 24–212.4 months), and the median MRI follow-up was 36.8 months (range 24–212.4 months). 47.6% of patients had an AVM with a Spetzler-Martin grade ≥ III. The median administered margin and maximum doses were 22 and 40 Gy, respectively. The overall obliteration rate was 70.5%. Of patients who showed complete obliteration, 74.4% developed AREs within 4–6 months after GKRS. Late-onset AREs (i.e., > 12 months) correlated to a failure to obliterate the nidus. 58.1% of patients who developed appreciable AREs (defined as ARE index > 8) proceeded to have a complete nidus obliteration. Appreciable AREs were found to be influenced by AVM nidus volume > 3 ml, lobar location, number of draining veins and feeding arteries, prior embolization, and higher margin dose. On the other hand, a minimum ARE index > 8 predicted obliteration (p = 0.043).
ARE development after radiosurgery follows a temporal pattern peaking at 7–12 months after stereotactic radiosurgery. The ARE index serves as an important adjunct tool in patient follow-up and outcome prediction.
Cheng-Chia Lee, Ching-Jen Chen, Benjamin Ball, David Schlesinger, Zhiyuan Xu, Chun-Po Yen and Jason Sheehan
Onyx, an ethylene-vinyl alcohol copolymer mixed in a dimethyl sulfoxide solvent, is currently one of the most widely used liquid materials for embolization of intracranial arteriovenous malformations (AVMs). The goal of this study was to define the risks and benefits of stereotactic radiosurgery (SRS) for patients who have previously undergone partial AVM embolization with Onyx.
Among a consecutive series of 199 patients who underwent SRS between January 2007 and December 2012 at the University of Virginia, 25 patients had Onyx embolization prior to SRS (the embolization group). To analyze the obliteration rates and complications, 50 patients who underwent SRS without prior embolization (the no-embolization group) were matched by propensity score method. The matched variables included age, sex, nidus volume before SRS, margin dose, Spetzler-Martin grade, Virginia Radiosurgery AVM Scale score, and median imaging follow-up period.
After Onyx embolization, 18 AVMs were reduced in size. Total obliteration was achieved in 6 cases (24%) at a median of 27.5 months after SRS. In the no-embolization group, total obliteration was achieved in 20 patients (40%) at a median of 22.4 months after SRS. Kaplan-Meier analysis demonstrated obliteration rates of 17.7% and 34.1% in the embolization group at 2 and 4 years, respectively. In the no-embolization group, the corresponding obliteration rates were 27.0% and 55.9%. The between-groups difference in obliteration rates after SRS did not achieve statistical significance. The difference in complications, including adverse radiation effects, hemorrhage episodes, seizure control, and patient mortality also did not reach statistical significance.
Onyx embolization can effectively reduce the size of many AVMs. This case-control study did not show any statistically significant difference in the rates of embolization or complications after SRS in patients who had previously undergone Onyx embolization and those who had not.
Jason P. Sheehan, Cheng-Chia Lee, Zhiyuan Xu, Colin J. Przybylowski, Patrick D. Melmer and David Schlesinger
Stereotactic radiosurgery (SRS) has been shown to offer a high probability of tumor control for Grade I meningiomas. However, SRS can sometimes incite edema or exacerbate preexisting edema around the targeted meningioma. The current study evaluates the incidence, timing, and degree of edema around parasagittal or parafalcine meningiomas following SRS.
A retrospective review was undertaken of a prospectively maintained database of patients treated with Gamma Knife radiosurgery at the University of Virginia Health System. All patients with WHO Grade I parafalcine or parasagittal meningiomas with at least 6 months of clinical follow-up were identified, resulting in 61 patients included in the study. The median radiographic follow-up was 28 months (range 6–158 months). Rates of new or worsening edema were quantitatively assessed using volumetric analysis; edema indices were computed as a function of time following radiosurgery. Statistical methods were used to identify favorable and unfavorable prognostic factors for new or worsening edema.
Progression-free survival at 2 and 5 years was 98% and 90%, respectively, according to Kaplan-Meier analysis. After SRS, new peritumoral edema occurred or preexisting edema worsened in 40% of treated meningiomas. The median time to onset of peak edema was 36 months post-SRS. Persistent and progressive edema was associated with 11 tumors, and resection was undertaken for these lesions. However, 20 patients showed initial edema progression followed by regression at a median of 18 months after radiosurgery (range 6–24 months). Initial tumor volume greater than 10 cm3, absence of prior resection, and higher margin dose were significantly (p < 0.05) associated with increased risk of new or progressive edema after SRS.
Stereotactic radiosurgery offers a high rate of tumor control in patients with parasagittal or parafalcine meningiomas. However, it can lead to worsening peritumoral edema in a minority of patients. Following radiosurgery, transient edema occurs earlier than persistent and progressive edema. Longitudinal follow-up of meningioma patients after SRS is required to detect and appropriately treat transient as well as progressive edema.
Cheng-Chia Lee, Hsiu-Mei Wu, Wen-Yuh Chung, Ching-Jen Chen, David Hung-Chi Pan and Sanford P. C. Hsu
Resection of vestibular schwannoma (VS) after Gamma Knife surgery (GKS) is infrequently performed. The goals of this study were to analyze and discuss the neurological outcomes and technical challenges of VS resection and to explore strategies for treating tumors that progress after GKS.
In total, 708 patients with VS underwent GKS between 1993 and 2012 at Taipei Veterans General Hospital. The post-GKS clinical courses, neurological presentations, and radiological changes in these patients were analyzed. Six hundred patients with imaging follow-up of at least 1 year after GKS treatment were included in this study.
Thirteen patients (2.2%) underwent microsurgery on average 36.8 months (range 3–107 months) after GKS. The indications for the surgery included symptomatic adverse radiation effects (in 4 patients), tumor progression (in 6), and cyst development (in 3). No morbidity or death as a result of the surgery was observed. At the last follow-up evaluation, all patients, except 1 patient with a malignant tumor, had stable or near-normal facial function.
For the few VS cases that require resection after radiosurgery, maximal tumor resection can be achieved with modern skull-based techniques and refined neuromonitoring without affecting facial nerve function.
Yi-Chieh Hung, Cheng-Chia Lee, Kang-Du Liu, Wen-Yuh Chung, David Hung-Chi Pan and Huai-Che Yang
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).
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).
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).
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.
Adeel Ilyas, Ching-Jen Chen, Dale Ding, Davis G. Taylor, Shayan Moosa, Cheng-Chia Lee, Or Cohen-Inbar and Jason P. Sheehan
Several recent studies have improved our understanding of the outcomes of volume-staged (VS) and dose-staged (DS) stereotactic radiosurgery (SRS) for the treatment of large (volume > 10 cm3) brain arteriovenous malformations (AVMs). In light of these recent additions to the literature, the aim of this systematic review is to provide an updated comparison of VS-SRS and DS-SRS for large AVMs.
A systematic review of the literature was performed using PubMed to identify cohorts of 5 or more patients with large AVMs who had been treated with VS-SRS or DS-SRS. Baseline data and post-SRS outcomes were extracted for analysis.
A total of 11 VS-SRS and 10 DS-SRS studies comprising 299 and 219 eligible patients, respectively, were included for analysis. The mean obliteration rates for VS-SRS and DS-SRS were 41.2% (95% CI 31.4%–50.9%) and 32.3% (95% CI 15.9%–48.8%), respectively. Based on pooled individual patient data, the outcomes for patients treated with VS-SRS were obliteration in 40.3% (110/273), symptomatic radiation-induced changes (RICs) in 13.7% (44/322), post-SRS hemorrhage in 19.5% (50/256), and death in 7.4% (24/323); whereas the outcomes for patients treated with DS-SRS were obliteration in 32.7% (72/220), symptomatic RICs in 12.2% (31/254), post-SRS hemorrhage in 10.6% (30/282), and death in 4.6% (13/281).
Volume-staged SRS appears to afford higher obliteration rates than those achieved with DS-SRS, although with a less favorable complication profile. Therefore, VS-SRS or DS-SRS may be a reasonable treatment approach for large AVMs, either as stand-alone therapy or as a component of a multimodality management strategy.