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David J. Schlesinger, Håkan Nordström, Anders Lundin, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

Patients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models.

METHODS

Leksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine–radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm.

RESULTS

Overall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = −0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = −0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm.

CONCLUSIONS

Onyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.

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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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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.

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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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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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Arnaldo Neves Da Silva, Kazuki Nagayama, David J. Schlesinger and Jason P. Sheehan

Object

Brain metastases from gastrointestinal cancers are rare. However, the incidence is increasing because patients with gastrointestinal carcinoma tend to live longer due to earlier diagnosis and more effective treatment of systemic disease. The purpose of this study was to evaluate the efficacy of Gamma Knife surgery (GKS) for the treatment of brain metastases from gastrointestinal cancers.

Methods

The authors performed a retrospective review of 40 patients (18 women and 22 men) who had undergone GKS to treat a total of 118 metastases from gastrointestinal cancers between January 1996 and December 2006. The mean patient age was 58.7 years, and the mean Karnofsky Performance Scale (KPS) score was 70. There were 7 patients with esophageal cancer, 25 with colon cancer, 5 with rectal cancer, 2 with pancreatic cancer, and 1 with gastric cancer. Nineteen patients were treated with whole-brain radiotherapy and/or local brain radiotherapy before GKS. Twenty-four patients had extracranial metastases, and 3 had an additional primary cancer. The mean metastatic brain tumor volume was 4.3 cm3, and the mean maximum tumor dose varied from 17.1 to 76.7 Gy (mean 41.8 Gy).

Results

Follow-up imaging studies were available in 25 patients with a total of 90 treated metastases. The results demonstrate a tumor control rate of 91%. The median survival time was 6.7 months, and the 6-month and 1-year survival rates were 55 and 25%, respectively. A univariate analysis revealed that the KPS score (≤ 70 vs ≥ 80) was significant (p = 0.018) for improved survival.

Conclusions

Results in this series suggest that GKS can be an effective tool for the treatment of brain metastases from gastrointestinal cancer.