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David Schlesinger, John Snell and Jason Sheehan

Object

The relative performances of two plugging strategies commonly used for pituitary adenoma dose plans were evaluated in terms of factors that influence dose plan quality.

Methods

Dose plans and clinical treatment data were obtained in 108 patients treated with the Model C Gamma Knife at the University of Virginia. These data were analyzed to determine factors (including plugging strategy) influencing the quality of the dose plans in terms of beam time, conformity, dose to the optic apparatus, and plugging burden.

For both secretory and nonsecreory adenomas, beam time (psecretory < 0.001, pnonsecretory = 0.015) and plugging burden (psecretory = 0.007, pnonsecretory = 0.038) were reduced when using the customized plugging strategy. The choice of plugging strategy was found to play no significant role in conformity or dose to the optic apparatus. Other factors found to play a significant role in adenoma dose plan quality included tumor volume, prescription dose, and distance from the target to the optic pathways.

Conclusions

While both plugging strategies were effective at providing the required protection to the optic pathways, the authors found that the customized plugging strategy provided more efficient performance in pituitary adenoma treatments.

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Christopher P. Cifarelli, David J. Schlesinger and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) has become a significant component of neurosurgical treatment for recurrent secretory and nonsecretory pituitary adenomas. Although the long-term risks of visual dysfunction following microsurgical resection of pituitary adenomas has been well studied, the comparable risk following radiosurgery is not well defined. This study evaluates the long-term risks of ophthalmological dysfunction following GKS for recurrent pituitary adenomas.

Methods

An analysis of 217 patients with recurrent secretory (n = 131) and nonsecretory (n = 86) pituitary adenomas was performed to determine the incidence of and risk factors for subsequent development of visual dysfunction. Patients underwent ophthalmological evaluation as part of post-GKS follow-up to assess for new or worsened cranial nerve II, III, IV, or VI palsies. The median follow-up duration was 32 months. The median maximal dose was 50 Gy, and the median peripheral dose was 23 Gy. A univariate analysis was performed to assess for risk factors of visual dysfunction post-GKS.

Results

Nine patients (4%) developed new visual dysfunctions, and these occurred within 6 hours to 34 months following radiosurgery. None of these 9 patients had tumor growth on post-GKS neuroimaging studies. Three of these patients had permanent deficits whereas in 6 the deficits resolved. Five of the 9 patients had prior GKS or radiotherapy, which resulted in a significant increase in the incidence of cranial nerve dysfunction (p = 0.0008). An increased number of isocenters (7.1 vs 5.0, p = 0.048) was statistically related to the development of visual dysfunction. Maximal dose, margin dose, optic apparatus dose, tumor volume, cavernous sinus involvement, and suprasellar extension were not significantly related to visual dysfunction (p >0.05).

Conclusions

Neurological and ophthalmological assessment in addition to routine neuroimaging and endocrinological follow-up are important to perform following GKS. Patients with a history of radiosurgery or radiation therapy are at higher risk of cranial nerve deficits. Also, a reduction in the number of isocenters delivered, along with volume treated, particularly in the patients with secretory tumors, appears to be the most reasonable strategy to minimize the risk to the visual system when treating recurrent pituitary adenomas with stereotactic radiosurgery.

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Claire Olson, Chun-Po Yen, David Schlesinger and Jason Sheehan

Object

Intracranial hemangiopericytoma is a rare CNS tumor that exhibits a high incidence of local recurrence and distant metastasis. The purpose of this study was to evaluate the role of Gamma Knife surgery (GKS) in the management of intracranial hemangiopericytomas.

Methods

In a review of the University of Virginia radiosurgery database between 1989 and 2008, the authors found recurrent or residual hemangiopericytomas after resection in 21 patients in whom radiosurgery was performed to treat 28 discrete tumors. The median age of this population was 47 years (range 31–61 years) at the time of the initial GKS. Prior treatments included embolization (6), transcranial resection (39), transsphenoidal resection (2), and fractionated radiotherapy (8). The mean prescription and maximum radiosurgical doses to the tumors were 17.0 and 40.3 Gy, respectively. Repeat radiosurgery was used to treat 13 tumors. The median follow-up period was 68 months (range 2–138 months).

Results

At last follow-up, local tumor control was demonstrated in 47.6% of the patients (10 of 21 patients) with hemangiopericytomas. Of the 28 tumors treated, 8 decreased in size on follow-up imaging (28.6%), 5 remained unchanged (17.9%), and 15 ultimately progressed (53.6%). The progression-free survival rates were 90, 60.3, and 28.7% at 1, 3, and 5 years after initial GKS. The progression-free survival rate improved to 95, 71.5, and 71.5% at 1, 3, and 5 years after multiple GKS treatments. The 5-year survival rate after radiosurgery was 81%. Prior fractionated irradiation or radiosurgical prescription dose did not correlate with tumor control. In 4 (19%) of 21 patients extracranial metastases developed.

Conclusions

Radiosurgery is a reasonable treatment option for recurrent hemangiopericytomas. Long-term close clinical and imaging follow-up is necessary because of the high probability of local recurrence and distant metastases. Repeat radiosurgery may be used to treat new or recurrent hemangiopericytomas over a long follow-up course.

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Mohamed Elsharkawy, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan

Object

Most intracranial schwannomas arise from cranial nerve (CN) VIII. Stereotactic radiosurgery is a mainstay of treatment for vestibular schwannomas. Intracranial schwannomas arising from other CNs are much less common. We evaluate the efficacy of Gamma Knife surgery on nonvestibular schwannomas including trigeminal, hypoglossal, abducent, facial, trochlear, oculomotor, glossopharyngeal, and jugular foramen tumors.

Methods

Thirty-six patients with nonvestibular schwannomas were treated at the University of Virginia Gamma Knife center from 1989 to 2008. The median patient age was 48 years (mean 45.6 years, range 10–72 years). Schwannomas arose from the following CNs: CN III (in 1 patient), CN IV (in 1), CN V (in 25), CN VI (in 2), CN VII (in 1), CN IX (in 1), and CN XII (in 3). In 2 patients, tumors arose from the jugular foramen. The median tumor volume was 2.9 cm3 (mean 3.3 cm3, range 0.07–8.8 cm3). The median margin dose was 13.5 Gy (range 9.3–20 Gy); the median maximum dose was 30 Gy (range 21.7–50.0 Gy).

Results

The mean and median follow-up times of 36 patients were 54 and 37 months, respectively (range 2–180 months). At the last radiological follow-up, the tumor size had decreased in 20 patients, remained stable in 9 patients, and increased in 7 patients. The 2-year actuarial progression-free survival was 91%. Higher maximum dose was statistically related to tumor control (p = 0.027).

Thirty-three patients had adequate clinical follow-up. Among them, 21 patients had improvement in their presenting symptoms, 8 patients were stable after treatment with no worsening of their presenting symptoms, 2 patients developed new symptoms, and 1 patient experienced symptom deterioration. Notably, 1 patient with neurofibromatosis Type 2 developed new symptoms that were unrelated to the tumor treated with Gamma Knife surgery.

Conclusions

Gamma Knife surgery is a reasonably effective treatment option for patients with nonvestibular schwannomas. Patients require careful follow-up for tumor progression and signs of neurological deterioration.

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Mohamed Samy Elhammady and Roberto C. Heros

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Jason P. Sheehan, Gregory Patterson, David Schlesinger and Zhiyuan Xu

Object

Obsessive-compulsive disorder (OCD) is a challenging psychiatric condition associated with anxiety and ritualistic behaviors. Although medical management and psychiatric therapy are effective for many patients, severe and extreme cases may prove refractory to these approaches. The authors evaluated their experience with Gamma Knife (GK) capsulotomy in treating patients with severe OCD.

Methods

A retrospective review of an institutional review board–approved prospective clinical GK database was conducted for patients treated for severe OCD. All patients were evaluated preoperatively by at least one psychiatrist, and their condition was deemed refractory to pharmacological and psychiatric therapy.

Results

Five patients were identified. Gamma Knife surgery with the GK Perfexion unit was used to target the anterior limb of the internal capsule bilaterally. A single 4-mm isocenter was used; maximum radiation doses of 140–160 Gy were delivered. All 5 patients were preoperatively and postoperatively assessed for clinical response by using both subjective and objective metrics, including the Yale-Brown Obsessive Compulsive Scale (YBOCS); 4 of the 5 patients had postoperative radiological follow-up. The median clinical follow-up was 24 months (range 6–33 months). At the time of radiosurgery, all patients had YBOCS scores in the severe or extreme range (median 32, range 31–34). At the last follow-up, 4 (80%) of the 5 patients showed marked clinical improvement; in the remaining patient (20%), mild improvement was seen. The median YBOCS score was 13 (range 12–31) at the last follow-up. Neuroimaging studies at 6 months after GK treatment demonstrated a small area of enhancement corresponding to the site of the isocenter and some mild T2 signal changes in the internal capsule. No adverse clinical effects were noted from the radiosurgery.

Conclusions

For patients with severe OCD refractory to medications and psychiatric therapy, GK capsulotomy afforded clinical improvement. Further study of this approach seems warranted.

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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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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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Adomas Bunevicius, Darrah Sheehan, Mary Lee Vance, David Schlesinger and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is used for the management of residual or recurrent Cushing’s disease (CD). Increasing experience and technological advancements of Gamma Knife radiosurgery (GKRS) systems can impact the outcomes of CD patients. The authors evaluated the association of their center’s growing experience and the era in which GKRS was performed with treatment success and adverse events in patients with CD.

METHODS

The authors studied consecutive patients with CD treated with GKRS at the University of Virginia since installation of the first Gamma Knife system in March 1989 through August 2019. They compared endocrine remission and complication rates between patients treated before 2000 (early cohort) and those who were treated in 2000 and later (contemporary cohort).

RESULTS

One hundred thirty-four patients with CD underwent GKRS during the study period: 55 patients (41%) comprised the early cohort, and 79 patients (59%) comprised the contemporary cohort. The contemporary cohort, compared with the early cohort, had a significantly greater treatment volume, radiation prescription dose, maximal dose to the optic chiasm, and number of isocenters, and they more often had cavernous sinus involvement. Endocrine remission rates were higher in the contemporary cohort when compared with the early cohort (82% vs 66%, respectively; p = 0.01). In a Cox regression analysis adjusted for demographic, clinical, and SRS characteristics, the contemporary GKRS cohort had a higher probability of endocrine remission than the early cohort (HR 1.987, 95% CI 1.234–3.199; p = 0.005). The tumor control rate, incidence of cranial nerve neuropathy, and new anterior pituitary deficiency were similar between the two groups.

CONCLUSIONS

Technological advancements over the years and growing center experience were important factors for improved endocrine remission rates in patients with CD. Technological aspects and results of contemporary Gamma Knife systems should be considered when counseling patients, planning treatment, and reporting treatment results. Studies exploring the learning curve for GKRS are warranted.

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David Schlesinger, Zhiyuan Xu, Frances Taylor, Chun-Po Yen and Jason Sheehan

Object

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.

Methods

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.

Results

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.

Conclusions

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.