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Cheng-Chia Lee and David Hung-Chi Pan

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Da Li and Jun-Ting Zhang

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Or Cohen-Inbar, Cheng-Chia Lee, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan

OBJECT

The authors review outcomes following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs) and their correlation to postradiosurgery adverse radiation effects (AREs).

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

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Cheng-Chia Lee, Chun-Po Yen, Zhiyuan Xu, David Schlesinger and Jason Sheehan

Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Mohana Rao Patibandla, Cheng-chia Lee, Athreya Tata, Gokul Chowdary Addagada and Jason P. Sheehan

OBJECTIVE

Research over the past 2 decades has been characterizing the role of stereotactic radiosurgery (SRS) in the treatment of benign intracranial tumors, including meningiomas. However, few studies have examined the long-term outcomes of SRS treatment for posterior fossa meningiomas (PFMs). Furthermore, previous studies have typically used single diameter measurements when reporting outcomes, which can yield misleading results. The authors describe the use of SRS in the treatment of benign WHO grade I PFMs and correlate volumetric analysis with long-term outcomes.

METHODS

This study is a retrospective analysis of a prospectively maintained IRB-approved database. Inclusion criteria were a diagnosis of WHO grade I PFM with subsequent treatment via single-session SRS and a minimum of 3 follow-up MRI studies available. Volumetric analysis was performed on the radiosurgical scan and each subsequently available follow-up scan by using slice-by-slice area calculations of the meningioma and numerical integration with the trapezoid rule.

RESULTS

The final cohort consisted of 120 patients, 76.6% (92) of whom were female, with a median age of 61 years (12–88 years). Stereotactic radiosurgery was the primary treatment for 65% (78) of the patients, whereas 28.3% (34) had 1 resection before SRS treatment and 6.7% (8) had 2 or more resections before SRS. One patient had prior radiotherapy. Tumor characteristics included a median volume of 4.0 cm3 (0.4–40.9 cm3) at treatment with a median margin dose of 15 Gy (8–20 Gy). The median clinical and imaging follow-ups were 79.5 (15–224) and 72 (6–213) months, respectively. For patients treated with a margin dose ≥ 16 Gy, actuarial progression-free survival rates during the period 2–10 years post-SRS were 100%. In patients treated with a margin dose of 13–15 Gy, the actuarial progression-free survival rates at 2, 4, 6, 8, and 10 years were 97.5%, 97.5%, 93.4%, 93.4%, and 93.4%, respectively. Those who were treated with ≤ 12 Gy had actuarial progression-free survival rates of 95.8%, 82.9%, 73.2%, 56.9%, and 56.9% at 2, 4, 6, 8, and 10 years, respectively. The overall tumor control rate was 89.2% (107 patients). Post-SRS improvement in neurological symptoms occurred in 23.3% (28 patients), whereas symptoms were stable in 70.8% (85 patients) and worsened in 5.8% (7 patients). Volumetric analysis demonstrated that a change in tumor volume at 3 years after SRS reliably predicted a volumetric change and tumor control at 5 years (R2 = 0.756) with a p < 0.001 and at 10 years (R2 = 0.421) with a p = 0.001. The authors also noted that the 1- to 5-year tumor response is predictive of the 5- to 10-year tumor response (R2 = 0.636, p < 0.001).

CONCLUSIONS

Stereotactic radiosurgery, as an either upfront or adjuvant treatment, is a durable therapeutic option for WHO grade I PFMs, with high tumor control and a low incidence of post-SRS neurological deficits compared with those obtained using alternate treatment modalities. Lesion volumetric response at the short-term follow-up of 3 years is predictive of the long-term response at 5 and 10 years.

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Or Cohen-Inbar, Athreya Tata, Shayan Moosa, Cheng-chia Lee and Jason P. Sheehan

OBJECTIVE

Parasellar meningiomas tend to invade the suprasellar, cavernous sinus, and petroclival regions, encroaching on adjacent neurovascular structures. As such, they prove difficult to safely and completely resect. Stereotactic radiosurgery (SRS) has played a central role in the treatment of parasellar meningiomas. Evaluation of tumor control rates at this location using simplified single-dimension measurements may prove misleading. The authors report the influence of SRS treatment parameters and the timing and volumetric changes of benign WHO Grade I parasellar meningiomas after SRS on long-term outcome.

METHODS

Patients with WHO Grade I parasellar meningiomas treated with single-session SRS and a minimum of 6 months of follow-up were selected. A total of 189 patients (22.2% males, n = 42) form the cohort. The median patient age was 54 years (range 19–88 years). SRS was performed as a primary upfront treatment for 44.4% (n = 84) of patients. Most (41.8%, n = 79) patients had undergone 1 resection prior to SRS. The median tumor volume at the time of SRS was 5.6 cm3 (0.2–54.8 cm3). The median margin dose was 14 Gy (range 5–35 Gy). The volumes of the parasellar meningioma were determined on follow-up scans, computed by segmenting the meningioma on a slice-by-slice basis with numerical integration using the trapezoidal rule.

RESULTS

The median follow-up was 71 months (range 6–298 months). Tumor volume control was achieved in 91.5% (n = 173). Tumor progression was documented in 8.5% (n = 16), equally divided among infield recurrences (4.2%, n = 8) and out-of-field recurrences (4.2%, n = 8). Post-SRS, new or worsening CN deficits were observed in 54 instances, of which 19 involved trigeminal nerve dysfunction and were 18 related to optic nerve dysfunction. Of these, 90.7% (n = 49) were due to tumor progression and only 9.3% (n = 5) were attributable to SRS. Overall, this translates to a 2.64% (n = 5/189) incidence of direct SRS-related complications. These patients were treated with repeat SRS (6.3%, n = 12), repeat resection (2.1%, n = 4), or both (3.2%, n = 6). For patients treated with a margin dose ≥ 16 Gy, the 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progression-free survival rates are 100%, 100%, 95.7%, 95.7%, 95.7%, 95.7%, and 95.7%, respectively. Patients treated with a margin dose < 16 Gy, had 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progression-free survival rates of 99.4%, 97.7%, 95.1%, 88.1%, 82.1%, 79.4%, and 79.4%, respectively. This difference was deemed statistically significant (p = 0.043). Reviewing the volumetric patient-specific measurements, the early follow-up volumetric measurements (at the 3-year follow-up) reliably predicted long-term volume changes and tumor volume control (at the 10-year follow-up) (p = 0.029).

CONCLUSIONS

SRS is a durable and minimally invasive treatment modality for benign parasellar meningiomas. SRS offers high rates of growth control with a low incidence of neurological deficits compared with other treatment modalities for meningiomas in this region. Volumetric regression or stability during short-term follow-up of 3 years after SRS was shown to be predictive of long-term tumor control.

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Jason P. Sheehan, Cheng-Chia Lee, Zhiyuan Xu, Colin J. Przybylowski, Patrick D. Melmer and David Schlesinger

OBJECT

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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Cheng-Chia Lee, Ching-Jen Chen, Benjamin Ball, David Schlesinger, Zhiyuan Xu, Chun-Po Yen and Jason Sheehan

OBJECT

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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Dylan Russell, Travis Peck, Dale Ding, Ching-Jen Chen, Davis G. Taylor, Robert M. Starke, Cheng-Chia Lee and Jason P. Sheehan

OBJECTIVE

Embolization of brain arteriovenous malformations (AVMs) prior to stereotactic radiosurgery (SRS) has been reported to negatively affect obliteration rates. The goal of this systematic review and meta-analysis was to compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and those of AVMs treated with SRS alone (SRS group).

METHODS

A literature review was performed using PubMed to identify studies with 10 or more AVM patients and obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to compare obliteration rates between the E+SRS and SRS groups.

RESULTS

Twelve articles comprising 1716 patients were eligible for analysis. Among the patients with radiological follow-up data, complete obliteration was achieved in 48.4% of patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978) in the SRS group. A meta-analysis of the pooled data revealed that the obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI 0.41–0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in 6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups, respectively. The annual post-SRS hemorrhage rate was 2.0%–6.5% and 0%–2.0% for the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%–6.7% and 0%–13.5% for the E+SRS and SRS groups, respectively.

CONCLUSIONS

Arteriovenous malformation treatment with combined embolization and SRS is associated with lower obliteration rates than those with SRS treatment alone. However, this comparison does not fully account for differences in the initial AVM characteristics in the E+SRS group as compared with those in the SRS group. Further studies are warranted to address these limitations.