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  • Author or Editor: Robert M. Starke x
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Or Cohen-Inbar, Robert M. Starke, Gabriella Paisan, Hideyuki Kano, Paul P. Huang, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, David Mathieu, Danilo Silva, Mahmoud Abbassy, Symeon Missios, John Y. K. Lee, Gene H. Barnett, Douglas Kondziolka, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM.

METHODS

Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7–324.7 months).

RESULTS

Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems.

CONCLUSIONS

Early obliteration (≤ 18 months post-SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy.

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Or Cohen-Inbar, Robert M. Starke, Hideyuki Kano, Gregory Bowden, Paul Huang, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, David Mathieu, Danilo Silva, Mahmoud Abbassy, Symeon Missios, John Y. K. Lee, Gene H. Barnett, Douglas Kondziolka, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS).

METHODS

Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7–325 months).

RESULTS

The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome.

CONCLUSIONS

SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

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Robert M. Starke, Hideyuki Kano, Dale Ding, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Chun-Po Yen, Caleb Feliciano, Rafael Rodgriguez-Mercado, Luis Almodovar, Daniel R. Pieper, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up.

METHODS

Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed.

RESULTS

The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1–20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.

CONCLUSIONS

GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.

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Dale Ding, Robert M. Starke, Hideyuki Kano, David Mathieu, Paul P. Huang, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients.

METHODS

The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs.

RESULTS

A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001).

CONCLUSIONS

Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

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Robert M. Starke, Dale Ding, Hideyuki Kano, David Mathieu, Paul P. Huang, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs.

METHODS

We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors.

RESULTS

The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8–17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5–35 Gy), and the mean follow-up was 92 months (range 12–266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs.

CONCLUSIONS

Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.

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Dale Ding, Robert M. Starke, Hideyuki Kano, John Y. K. Lee, David Mathieu, John Pierce, Paul P. Huang, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Douglas Kondziolka, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes.

METHODS

The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses.

RESULTS

The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis.

CONCLUSIONS

Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

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Mohana Rao Patibandla, Dale Ding, Hideyuki Kano, Robert M. Starke, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.

METHODS

The authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988–2000) or modern (2001–2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).

RESULTS

The study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.

CONCLUSIONS

Despite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.