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Dibyendu Kumar Ray, Chun Po Yen, Mary Lee Vance, Edward R. Laws, Beatriz Lopes and Jason P. Sheehan

Lymphocytic hypophysitis is a relatively uncommon autoimmune inflammatory disorder affecting the pituitary gland. It most frequently occurs in women of child-bearing age. The authors report on their experience with a patient who presented with diplopia and marked enlargement of the pituitary gland. She underwent transsphenoidal surgery, and histopathological analysis confirmed the diagnosis of lymphocytic hypophysitis. The disease proved refractory to resection, and any attempt at withdrawal of corticosteroid therapy resulted in a return of the patient's symptoms and enlargement of the sellar contents.

The patient underwent Gamma Knife surgery (GKS) to the sella and both cavernous sinuses. After GKS, the patient was able to discontinue steroid therapy without return of her symptoms. Follow-up MR images demonstrated no evidence of recurrence of lymphocytic hypophysitis.

For persistent lymphocytic hypophysitis, GKS is a reasonable treatment option.

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Bhuvaneswara R. Basina, Claire Olson, Dibyendu Kumar Roy, Chun-Po Yen, David Schlesinger, Kazuki Nagayama and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) is frequently used to treat patients with metastasis to the brain. Radiosurgery seeks to limit radiation to the brain tissue surrounding the metastatic deposits. In patients with such lesions, a low radiation dose to the eloquent brain may help to prevent adverse effects. In this study the authors aimed to quantify the radiosurgical dose delivered to the anterior temporal structures in cases of metastatic brain lesions. They also evaluated the incidence and timing of new metastases in the anterior temporal lobes (ATLs) in patient cohorts that underwent GKS with or without whole-brain radiation therapy (WBRT).

Methods

The authors retrospectively analyzed 100 patients with metastatic brain lesions treated with GKS at the University of Virginia Health System. The anterior 5 cm of the temporal lobes and the hippocampi within the ATLs were contoured on the Gamma Knife planning station. Using the dose-volume histogram function in GammaPlan, treatment parameters for the metastases as well as radiation doses to the contoured ATLs and hippocampi were measured. Patients had clinical and MR imaging follow-ups at 3-month intervals. The ATLs and hippocampal regions were evaluated for the formation of new metastases on follow-up imaging.

Results

The demographic data—age, sex, Karnofsky Performance Scale score, number of temporal metastases at the time of GKS, total volume of metastatic tumors per patient, and number of intracranial metastatic deposits—were similar in the 2 cohorts. In patients without an ATL metastasis at the time of GKS, the mean maximum, 50% volume, and integral doses of radiation to the anterior temporal structures were very low: 2.6 Gy, 0.6 Gy, and 36.3 mJ in the GKS cohort and 2.1 Gy, 0.6 Gy, and 40.9 mJ in the GKS+WBRT cohort, respectively. Among the ATLs that had not shown a brain metastasis at the time of GKS, 8 of 92 temporal lobes in the GKS cohort and 10 of 89 in the GKS+WBRT cohort demonstrated a new anterior temporal lesion on follow-up MR imaging.

Conclusions

Gamma Knife surgery delivered a low dose of background radiation to the ATLs and hippocampi. The incidence of a new ATL metastasis in the GKS cohort was not higher than in the GKS+WBRT cohort. Gamma Knife surgery in the management of brain metastases limits the delivery of radiation to eloquent brain tissue without evidence of an appreciable propensity to develop new metastatic disease in the ATLs or hippocampi. This therapeutic approach may help to avoid unintended neurological dysfunction due to nonspecific delivery of radiation to eloquent brain tissues.

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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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Editorial

Radiosurgery in cavernous malformations: anatomy of a controversy

Ladislau Steiner, Bengt Karlsson, Chun-Po Yen, James C. Torner, Christer Lindquist and David Schlesinger

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Jason P. Sheehan, Dibyendu Kumar Ray, Stephen Monteith, Chun Po Yen, James Lesnick, Ronald Kersh and David Schlesinger

Object

Trigeminal neuralgia is believed to be related to vascular compression of the affected nerve. Radiosurgery has been shown to be reasonably effective for treatment of medically refractory trigeminal neuralgia. This study explores the rate of occurrence of MR imaging–demonstrated vascular impingement of the affected nerve and the extent to which vascular impingement affects pain relief in a population of trigeminal neuralgia patients undergoing Gamma Knife radiosurgery (GKRS).

Methods

The authors performed a retrospective analysis of 106 cases involving patients treated for typical trigeminal neuralgia using GKRS. Patients with or without single-vessel impingement on CISS MR imaging sequences and with no previous surgery were included in the study. Pain relief was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at the last follow-up. Degree of impingement, nerve diameter preand post-impingement, isocenter placement, and dose to the point of maximum impingement were evaluated in relation to the improvement of BNI score.

Results

The overall median follow-up period was 31 months. Overall, a BNI pain score of 1 was achieved in 59.4% of patients at last follow-up. Vessel impingement was seen in 63 patients (59%). There was no significant difference in pain relief between those with and without vascular impingement following GKRS (p > 0.05).

In those with vascular impingement on MR imaging, the median fraction of vessel impingement was 0.3 (range 0.04–0.59). The median dose to the site of maximum impingement was 42 Gy (range 2.9–79 Gy). Increased dose (p = 0.019) and closer proximity of the isocenter to the site of maximum vessel impingement (p = 0.012) correlated in a statistically significant fashion with improved BNI scores in those demonstrating vascular impingement on the GKRS planning MR imaging

Conclusions

Vascular impingement of the affected nerve was seen in the majority of patients with trigeminal neuralgia. Overall pain relief following GKRS was comparable in those with and without evidence of vascular compression on MR imaging. In subgroup analysis of those with MR imaging evidence of vessel impingement of the affected trigeminal nerve, pain relief correlated with a higher dose to the point of contact between the impinging vessel and the trigeminal nerve. Such a finding may point to vascular changes affording at least some degree of relief following GKRS for trigeminal neuralgia.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010

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Editorial

Arteriovenous malformations

Douglas Kondziolka

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Chun Po Yen, Stephen J. Monteith, James H. Nguyen, Jessica Rainey, David J. Schlesinger and Jason P. Sheehan

Object

The aim of this study was to evaluate the long-term imaging and clinical outcomes of intracranial arteriovenous malformations (AVMs) in children treated with Gamma Knife surgery (GKS).

Methods

Between 1989 and 2007, 200 patients with AVMs who were 18 years of age or younger were treated at the University of Virginia Health System. Excluding 14 patients who had not reached 2-year follow-up, 186 patients comprised this study. Hemorrhage was the most common presenting symptom leading to the diagnosis of AVMs (71.5%). The mean nidus volume was 3.2 cm3 at the time of GKS, and a mean prescription dose of 21.9 Gy was used.

Results

After initial GKS, 49.5% of patients achieved total angiographic obliteration. Forty-one patients whose AVM nidi remained patent underwent additional GKS. The obliteration rate increased to 58.6% after a second or multiple GKS. Subtotal obliteration was achieved in 9 patients (4.8%). Forty-nine patients (26.3%) still had a patent residual nidus. In 19 patients (10.2%), obliteration was confirmed on MR imaging only. Ten patients had 17 hemorrhages during the follow-up period. The hemorrhage rate was 5.4% within 2 years after GKS and 0.8% between 2 and 5 years. Six patients developed neurological deficits along with the radiation-induced changes. Two patients developed asymptomatic meningiomas 10 and 12 years after GKS. After a mean clinical follow-up of 98 months, less than 4% of patients had difficulty attending school or developing a career.

Conclusions

Gamma Knife surgery offers a reasonable chance of obliteration of an AVM in pediatric patients. The incidence of symptomatic radiation-induced changes is relatively low; however, long-term clinical and imaging follow-up is required to identify delayed cyst formation and secondary tumors.

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David J. Schlesinger, Faisal T. Sayer, Chun-Po Yen and Jason P. Sheehan

Object

Treatment planning for Gamma Knife surgery has traditionally been a forward planning (FP)–only approach with results that depend significantly on the experience of the user. Leksell GammaPlan version 10.0, currently in beta testing, introduces a new inverse planning (IP) engine that may allow more reproducible results across dosimetrists and individual institutions. In this study the authors compared the FP and IP approaches to Gamma Knife surgery.

Methods

Forty-three patients with pituitary adenomas were evaluated after dose planning was performed using FP and IP treatment approaches. Treatment plans were compared for target coverage, target selectivity, Paddick gradient index, number of isocenters, optic pathways dose, and treatment time. Differences between the forward and inverse treatment plans were evaluated in a statistical fashion.

Results

The IP software generated a dose plan within approximately 10 minutes. The FP approach delivered the prescribed isodose to a larger treatment volume than the IP system (p < 0.001). The mean (± SD) FP and IP coverage indices were 0.85 ± 0.23 and 0.85 ± 0.13, respectively (no significant difference). The mean FP and IP gradient indices were 2.78 ± 0.20 and 3.08 ± 0.37, respectively (p < 0.001). The number of isocenters did not appreciably differ between approaches. The maximum doses directed to the optic apparatus for the FP and IP methods were 8.67 ± 1.97 Gy and 12.33 ± 5.86 Gy, respectively (p < 0.001).

Conclusions

The Leksell GammaPlan IP system was easy to operate and provided a reasonable, first approximation dose plan. Particularly in cases in which there are eloquent structures at risk, experience and user-based optimization will be required to achieve an acceptable Gamma Knife dose plan.

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Jason P. Sheehan, Chun-Po Yen, James Nguyen, Jessica A. Rainey, Kasandra Dassoulas and David J. Schlesinger

Object

Stereotactic radiosurgery has been shown to afford a reasonable chance of local tumor control. However, new brain metastasis can arise following successful local tumor control from radiosurgery. This study evaluates the timing, number, and risk factors for development of subsequent new brain metastasis in a group of patients treated with stereotactic radiosurgery alone.

Methods

One hundred seventeen patients with histologically confirmed metastatic cancer underwent Gamma Knife surgery (GKS) to treat all brain metastases demonstrable on MR imaging. Patients were followed clinically and radiologically at approximately 3-month intervals for a median of 14.4 months (range 0.37–51.8 months). Follow-up MR images were evaluated for evidence of new brain metastasis formation. Statistical analyses were performed to determine the timing, number, and risk factors for development of new brain metastases.

Results

The median time to development of a new brain metastasis was 8.8 months. Patients with 3 or more metastases at the time of initial radiosurgery or those with cancer histologies other than non–small cell lung carcinoma were found to be at increased risk for early formation of new brain metastasis (p < 0.05). The mean number of new metastases per patient was 1.6 (range 0–11). Those with a higher Karnofsky Performance Scale score at the time of initial GKS were significantly more likely to develop a greater number of brain metastases by the last follow-up evaluation.

Conclusions

The timing and number of new brain metastases developing in patients treated with GKS alone is not inconsequential. Those with 3 or more metastases at the time of radiosurgery and those with cancer histology other than non–small cell lung carcinoma were at greater risk of early formation of new brain metastasis. Frequent follow-up evaluations, such as at 3-month intervals, appears appropriate in this patient population, particularly in high-risk patients. When detected early, salvage treatments including repeat radiosurgery can be used to treat new brain metastasis.