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Radiosurgery for dural carotid-cavernous sinus fistulas: Gamma Knife compared with XKnife radiosurgery

Clinical article

Hung-Chuan Pan, Ming-Hsi Sun, Jason Sheehan, Meei-Ling Sheu, Clayton Chi-Chang Chen, Hsu-Tung Lee, Wen-Ta Chiu, and Dar-Yu Yang

Object

In the modern era, stereotactic radiosurgery is an important part of the multidisciplinary and multimodality approach used to treat dural carotid-cavernous fistulas (DCCFs). Based on the ease of performance of techniques to fuse cerebral angiography studies with MR images or CT scans during the radiosurgical procedure, the Gamma Knife and XKnife are 2 of the most popular radiosurgical instruments for patients with DCCF. In this study, the authors compared the efficacy, neurological results, and complications associated with these 2 radiosurgical devices when used for DCCF.

Methods

Records for 41 patients with DCCF (15 treated using the XKnife and 26 with Gamma Knife surgery [GKS]) were retrieved from a radiosurgical database encompassing the period of September 2000 to August 2008. Among these patients, at least 2 consecutive MR imaging or MR angiography studies obtained after radiosurgery were available for determining radiological outcome of the fistula. All patients received regular follow-up to evaluate the neurological and ophthalmological function at an interval of 1–3 months. The symptomatology, obliteration rate, radiation dose, instrument accuracy, and adverse effects were determined for each group and compared between 2 groups. The data were analyzed using the Student t-test.

Results

The mean age of the patients was 63 ± 2.6 years, and the mean follow-up period was 63.1 ± 4.4 months (mean ± SD). Thirty-seven patients (90%) achieved an obliteration of the DCCF (93% in the XKnife cohort and 88% for the GKS cohort). In 34 of 40 patients (85%) with chemosis and proptosis of the eyes, these symptoms were resolved after treatment (4 had residual fistula and 2 had arterializations of sclera). All 5 patients with high intraocular pressure demonstrated clinical improvement. Ten (71%) of 14 patients with cranial nerve palsy demonstrated improvement following radiosurgery. Significant discrepancies of treatment modalities existed between the XKnife and GKS groups, such as radiation volume, conformity index, number of isocenters, instrument accuracy, peripheral isodose line, and maximum dosage. The XKnife delivered significantly higher radiation dosage to the lens, optic nerve, optic chiasm, bilateral temporal lobe, and brainstem. Few adverse events occurred, but included 1 patient with optic neuritis (GKS group), 1 intracranial hemorrhage (XKnife group), 1 brainstem edema (XKnife), and 3 temporal lobe radiation edemas (XKnife).

Conclusions

Radiosurgery affords a substantial chance of radiological and clinical improvement in patients with DCCFs. The Gamma Knife and XKnife demonstrated similar efficacy in the obliteration of DCCFs. However, a slightly higher incidence of complications occurred in the XKnife group.

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Editorial

Radiosurgery and cavernous malformations

Jason Sheehan and David Schlesinger

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Trans-sodium crocetinate enhancing survival and glioma response on magnetic resonance imaging to radiation and temozolomide

Laboratory investigation

Jason Sheehan, Christopher P. Cifarelli, Kasandra Dassoulas, Claire Olson, Jessica Rainey, and Shaojie Han

Object

Glioblastoma (GB) tumors typically exhibit regions of hypoxia. Hypoxic areas within the tumor can make tumor cells less sensitive to chemotherapy and radiation therapy. Trans-sodium crocetinate (TSC) has been shown to transiently increase oxygen to hypoxic brain tumors. The authors examined whether this improvement in intratumor oxygenation translates to a therapeutic advantage when delivering standard adjuvant treatment to GBs.

Methods

The authors used C6 glioma cells to create a hypoxic GB model. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Fifteen days later, MR imaging was used to confirm the presence of a glioma. The animals were randomly assigned to 1 of 3 groups: 1) temozolomide alone (350 mg/m2/day for 5 days); 2) temozolomide and radiation therapy (8 Gy); or 3) TSC (100 μg/kg for 5 days), temozolomide, and radiation therapy. Animals were followed through survival studies, and tumor response was assessed on serial MR images obtained at 15-day intervals during a 2-month period.

Results

Mean survival (± SEM) of the temozolomide-alone and the temozolomide/radiotherapy groups was 23.2 ± 0.9 and 29.4 ± 4.4 days, respectively. Mean survival in the TSC/temozolomide/radiotherapy group was 39.8 ± 6 days, a statistically significant improvement compared with either of the other groups (p < 0.05).

Although tumor size was statistically equivalent in all groups at the time of treatment initiation, the addition of TSC to temozolomide and radiotherapy resulted in a statistically significant reduction in the MR imaging–documented mean tumor size at 30 days after tumor implantation. The mean tumor size in the TSC/temozolomide/radiotherapy group was 18.9 ± 6.6 mm2 compared with 42.1 ± 2.7 mm2 in the temozolomide-alone group (p = 0.047) and 35.8 ± 5.1 mm2 in the temozolomide/radiation group (p = 0.004).

Conclusions

In a hypoxic GB model, TSC improves the radiological and clinical effectiveness of temozolomide and radiation therapy. Further investigation of this oxygen diffusion enhancer as a radiosensitizer for hypoxic brain tumors seems warranted.

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Editorial

Radiation oncology partnership and its impact on neurosurgery

Jason Sheehan

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Radiosurgery for intracranial hemangiopericytomas: outcomes after initial and repeat Gamma Knife surgery

Clinical article

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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Stereotactic radiosurgery: quo vadis?

Jason Sheehan and Nader Pouratian

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Editorial

Gamma Knife surgery and brain metastases

Fredric B. Meyer

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Effect of trans sodium crocetinate on brain tumor oxgenation

Laboratory investigation

Jason Sheehan, Jonathan Sherman, Christopher Cifarelli, Jay Jagannathan, Kasandra Dassoulas, Claire Olson, Jessica Rainey, and Shaojie Han

Object

Glioblastoma multiforme tumors typically exhibit regions of hypoxia. Hypoxic regions within the tumor make cells less sensitive to radiosurgery and radiation therapy. Trans sodium crocetinate (TSC) has been shown to be a radiosensitizer. The goal of this research was to elucidate the underlying mechanism of TSC's radiosensitizing effect.

Methods

A rat C6 glioma model was used. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Two weeks later, MR imaging was used to confirm the presence of a glioma. Following demonstration on MR imaging of a brain tumor, animals were randomized into 1 of 2 groups: 1) TSC alone (100 μg/kg), or 2) saline control. Licox probes were inserted into the brain tumor and contralateral cerebral hemisphere. Tissue oxygenation measurements were recorded before and after intravenous infusion of either TSC or saline.

Results

Not surprisingly, tissue oxygenation measurements revealed that the brain tumor was hypoxic relative to the contralateral cerebral hemisphere brain tissue. Two to 8 minutes after TSC was infused, tissue oxygenation measurements in the brain tumor increased above baseline by as much as 60%. After this temporary elevation following TSC infusion, tumor oxygenation measurements returned to baseline. No significant elevations in tissue oxygenation were seen on the contralateral side. Similarly, the saline vehicle was not observed to increase tissue oxygenation in either the brain tumor or the contralateral brain tissue.

Conclusions

Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.

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Gamma Knife surgery: past to Perfexion

Jason Sheehan

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Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery

Hung-Chuan Pan, Ming-Hsih Sun, Clayton Chi-Chang Chen, Chun-Jung Chen, Chen-Hui Lee, and Jason Sheehan

Object

Gamma Knife surgery (GKS) has been shown to be effective for treating many patients with brain metastasis. Some brain metastases demonstrate significant peritumoral edema; radiation may induce cerebral edema or worsening preexisting edema. This study was conducted to evaluate the imaging and neurobehavioral outcomes in patients with preexisting peritumoral edema who then undergo GKS.

Methods

Between August 2003 and January 2008, 63 cases of brain metastasis with significant peritumoral edema (> 20 cm3) were prospectively studied. The study inclusion criteria were as follows: 1) a single metastatic lesion with significant edema (perilesional edema signal volume on FLAIR > 20 cm3); and 2) inclusion of only 1 lesion > 20 cm3 in the study (in cases of multiple lesions noted on FLAIR images). All patients received MR imaging with pulse sequences including T1-weighted imaging and FLAIR with or without contrast and T2-weighted imaging at an interval of 3 months. A neurological assessment and Brain Cancer Module (BCM-20) questionnaire were obtained every 2–3 months. Kaplan–Meier, Cox regression, and logistic regression were used for analysis of survival and associated factors.

Results

At the time of GKS, the median Karnofsky Performance Scale (KPS) score was 70 (range 50–90), and the mean BCM-20 score was 45.5 ± 6.1. The mean tumor volume (± standard deviation) was 5.2 ± 4.6 cm3 with corresponding T2-weighted imaging and FLAIR volumes of 59.25 ± 37.3 and 62.1 ± 38.8 cm3, respectively (R2 = 0.977, p < 0.001). The mean edema index (volume of peritumoral edema/tumor volume) was 17.5 ± 14.5. The mean peripheral and maximum GKS doses were 17.4 ± 2.3 and 35 ± 4.7 Gy, respectively. The median survival was 11 months. The longer survival was related to KPS scores ≥ 70 (p = 0.008), age < 65 years (p = 0.022), and a reduction of > 6 in BCM-20 score (p = 0.007), but survival was not related to preexisting edema or tumor volume. A reduction in BCM-20 score of > 6 was related to decreased volume in T1-weighted and FLAIR imaging (p < 0.001). Thirty-eight (79.2%) of 48 patients demonstrated decreased tumor volume and accompanied by decreased T2-weighted imaging and FLAIR volume. Eight (16.7%) of the 48 patients exhibited increased or stable tumor volume. A margin dose > 18 Gy was more likely to afford tumor reduction and resolution of peritumoral edema (p = 0.005 and p = 0.006, respectively). However, prior external-beam radiation therapy correlated with worsened preexisting peritumoral edema (p = 0.013) and longer maintenance of corticosteroids (p < 0.001).

Conclusions

Patients demonstrating a reduction in the BCM-20 score > 6, age < 65 years, and KPS score ≥ 70 exhibited longer survival. Significant preexisting edema did not influence the tumor response or clinical outcome. The resolution of edema was related to better quality of life but not to longer survival.