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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan J. McShane, John Lee, Mohana Rao Patibandla, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Christopher P. Cifarelli, Gabriella Paisan, John Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Nanthiya Sujijantarat, Charles Matouk, Veronica Chiang, Judith Hess, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).

METHODS

Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.

RESULTS

A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2–3 dAVFs and Borden type 2–3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).

CONCLUSIONS

Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.

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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan McShane, John Lee, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Mohana Rao Patibandla, Christopher P. Cifarelli, Gabriella Paisan, John A. Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome.

METHODS

Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose.

RESULTS

A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5–18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration.

CONCLUSIONS

GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

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Kyung-Jae Park, Hideyuki Kano, Aditya Iyer, Xiaomin Liu, Daniel A. Tonetti, Craig Lehocky, Andrew Faramand, Ajay Niranjan, John C. Flickinger, Douglas Kondziolka, and L. Dade Lunsford

OBJECTIVE

The authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).

METHODS

The authors retrospectively assessed treatment outcomes 5–18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22–83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1–37.3 cm3), and the median margin dose was 13.0 Gy (range 10–20 Gy).

RESULTS

Tumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year follow-ups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8–120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438–12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041–0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3–85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026–12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.

CONCLUSIONS

This long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

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Hideyuki Kano, John C. Flickinger, Aya Nakamura, Rachel C. Jacobs, Daniel A. Tonetti, Craig Lehocky, Kyung-Jae Park, Huai-che Yang, Ajay Niranjan, and L. Dade Lunsford

OBJECTIVE

The management of large-volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains challenging. The authors retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percentage volume of an AVM that receives a minimal threshold dose of radiation.

METHODS

In 1992, the authors prospectively began to stage anatomical components in order to deliver higher single doses to AVMs > 15 cm3 in volume. Since that time 60 patients with large AVMs have undergone volume-staged SRS (VS-SRS). The median interval between the first stage and the second stage was 4.5 months (2.8–13.8 months). The median target volume was 11.6 cm3 (range 4.3–26 cm3) in the first-stage SRS and 10.6 cm3 (range 2.8–33.7 cm3) in the second-stage SRS. The median margin dose was 16 Gy (range 13–18 Gy) for both SRS stages.

RESULTS

AVM obliteration after the initial two staged volumetric SRS treatments was confirmed by MRI alone in 4 patients and by angiography in 11 patients at a median follow-up of 82 months (range 0.4–206 months) after VS-SRS. The post–VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and 27% at 10 years. In multivariate analysis, only ≥ 20-Gy volume coverage was significantly associated with higher total obliteration rates confirmed by angiography. When the margin dose is ≥ 17 Gy and the 20-Gy SRS volume included ≥ 63% of the total target volume, the angiographically confirmed obliteration rates increased to 61% at 5 years and 70% at 10 years.

CONCLUSIONS

The outcomes of prospective VS-SRS for large AVMs can be improved by prescribing an AVM margin dose of ≥ 17 Gy and adding additional isocenters so that ≥ 63% of the internal AVM dose receives more than 20 Gy.

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Daniel A. Tonetti, Bradley A. Gross, Brian T. Jankowitz, Hideyuki Kano, Edward A. Monaco III, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

Aggressive dural arteriovenous fistulas (dAVFs) with cortical venous drainage (CVD) are known for their relatively high risk of recurrent neurological events or hemorrhage. However, recent natural history literature has indicated that nonaggressive dAVFs with CVD have a significantly lower prospective risk of hemorrhage. These nonaggressive dAVFs are typically diagnosed because of symptomatic headache, pulsatile tinnitus, or ocular symptoms, as in low-risk dAVFs. Therefore, the viability of stereotactic radiosurgery (SRS) as a treatment for this lesion subclass should be investigated.

METHODS

The authors evaluated their institutional experience with SRS for dAVFs with CVD for the period from 1991 to 2016, assessing angiographic outcomes and posttreatment hemorrhage rates. They subsequently pooled their results with those published in the literature and stratified the results based on the mode of clinical presentation.

RESULTS

In an institutional cohort of 42 dAVFs with CVD treated using SRS, there were no complications or hemorrhages after treatment in 19 patients with nonaggressive dAVFs, but there was 1 radiation-induced complication and 1 hemorrhage among the 23 patients with aggressive dAVFs. In pooling these cases with 155 additional cases from the literature, the authors found that the hemorrhage rate after SRS was significantly lower among the patients with nonaggressive dAVFs (0% vs 6.8%, p = 0.003). Similarly, the number of radiation-related complications was 0/124 in nonaggressive dAVF cases versus 6/73 in aggressive dAVF cases (p = 0.001). The annual rate of hemorrhage after SRS for aggressive fistulas was 3.0% over 164.5 patient-years, whereas none of the nonaggressive fistulas bled after radiosurgery over 279.4 patient-years of follow-up despite the presence of CVD.

CONCLUSIONS

Cortical venous drainage is thought to be a significant risk factor in all dAVFs. In the institutional experience described here, SRS proved to be a low-risk strategy associated with a very low risk of subsequent hemorrhage or radiation-related complications in nonaggressive dAVFs with CVD.

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Daniel A. Tonetti, Bradley A. Gross, Kyle M. Atcheson, Brian T. Jankowitz, Hideyuki Kano, Edward A. Monaco III, Ajay Niranjan, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

The authors of this study found that, given the latency period required for arteriovenous malformation (AVM) obliteration after stereotactic radiosurgery (SRS), a study with limited follow-up cannot assess the benefit of SRS for unruptured AVMs.

METHODS

The authors reviewed their institutional experience with “ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)–eligible” AVMs treated with SRS between 1987 and 2016, with the primary outcome defined as stroke (ischemic or hemorrhagic) or death (AVM related or AVM unrelated). Patients with at least 3 years of follow-up in addition to those who experienced stroke or died during the latency period were included. Secondary outcome measures included obliteration rates, patients with new seizure disorders, and those with new focal deficits without stroke.

RESULTS

Of 233 patients included in this study, 32 had a stroke or died after SRS over the mean 8.4-year follow-up (14%). Utilizing the 10% stroke or death rate at a mean 2.8-year follow-up for untreated AVMs in ARUBA, the rate in the authors’ study is significantly lower than that anticipated at the 8.4-year follow-up for an untreated cohort (14% vs 30%, p = 0.0003). Notwithstanding obliteration, in this study, annualized rates of hemorrhage and stroke or death after 3 years following SRS were 0.4% and 0.8%, respectively. The overall obliteration rate was 72%; new seizure disorders, temporary new focal deficits without stroke, and permanent new focal deficits without stroke occurred in 2% of patients each.

CONCLUSIONS

After a sensible follow-up period exceeding the latency period, there is a lower rate of stroke/death for patients with treated, unruptured AVMs with SRS than for patients with untreated AVMs.