Faculty Bibliography

OBJECTIVE Due to the complexity of Spetzler-Martin (SM) Grade IV-V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV-V AVMs and determine predictive factors. METHODS The authors retrospectively pooled data from 233 patients (mean age 33 years) with SM Grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at 8 participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm³, 17.3 Gy, and 84.5 months, respectively. Statistical analyses were performed to identify factors associated with post-SRS outcomes. RESULTS At a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (p = 0.04) was found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM Grade IV-V AVMs compared with ruptured ones (p = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (p = 0.024) and radiologically evident RIC (p = 0.05) in the respective multivariate analyses. CONCLUSIONS In this multi-institutional study, single-session SRS had limited efficacy in the management of SM Grade IV-V AVMs. Favorable outcome was only achieved in a minority of unruptured SM Grade IV-V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume-staged SRS approach for large AVMs represents an alternative approach for high-grade AVMs, but it requires further investigation.

BACKGROUND:The effect of age on adult brain arteriovenous malformations (AVM) outcomes after stereotactic radiosurgery (SRS) remains unclear. The study aim is to compare AVM outcomes between elderly (age ≥60 years) and non-elderly adult patients. METHODS:We retrospectively reviewed pooled data comprising patients who underwent SRS for AVMs between 1987 and 2014 at eight centers participating in the International Gamma Knife Research Foundation. Adult (age ≥18 years) patients with ≥12 months follow-up were dichotomized into elderly and non-elderly cohorts, and matched in a 1:1 ratio. Favorable outcome was AVM obliteration without permanent symptomatic radiation-induced changes (RIC) or post-SRS hemorrhage. RESULTS:The study cohort consisted of 1,845 patients (elderly n=188 vs. nonelderly n=1,657) who met the inclusion criteria, and subsequent matching resulted in 181 patients in each cohort. In the matched cohorts, rates of obliteration (54.7% vs. 64.6%, p=0.054) favorable outcome (51.4% vs. 61.3%, p=0.056) were no different between the elderly and nonelderly cohorts. The rates of post-SRS hemorrhage (9.9% vs. 5.5%, p=0.115), RIC (26.5% vs. 30.9%, p=0.353), symptomatic RIC (9.4% vs. 9.4%, p=1.000), and permanent symptomatic RIC (3.3% vs. 2.2%, p=0.750) were also not significantly different between the elderly and non-elderly cohorts. Elderly AVM patients did have a significantly higher rate of all-cause mortality (27.7% vs. 5.5%, p<0.001). CONCLUSION/CONCLUSIONS:Advanced age does not appear to significantly impact obliteration or complication rates after SRS for AVMs. Although the decision to recommend intervention for AVMs in the elderly population is multifactorial, SRS may be a viable modality when treatment is deemed appropriate.

BACKGROUND: The utility of radiosurgery is not well documented for pilocytic astrocytoma. We analyzed the efficacy and prognostic factors associated with Gamma Knife radiosurgery (GKRS) for pilocytic astrocytoma in an international multicenter trial. METHODS: Nine medical centers from the International Gamma Knife Research Foundation provided data. Patients treated with single session GKRS with histologic diagnosis of pilocytic astrocytoma were eligible. Patient, tumor, and treatment variables were analyzed. RESULTS: 141 patients with a median age 13.9 years (range: 2-84) were included. Median follow up was 67.3 months. Twenty-one (15%) had radiotherapy (RT) and 11 (8%) had chemotherapy prior to GKRS. Median margin dose: 14 Gy (range: 4-22.5). Median tumor volume:3.45cc (range: 0.17-33.7). Overall survival at 3, 5 and 10 years from GKRS was 96.8%, 95.7% and 92.5%, respectively. Thirty-four patients progressed resulting in progression-free survival (PFS) at 3, 5, and 10 years of 80.8%, 74.0%, and 69.7%, respectively. For patients <18 years old, 3, 5, and 10 year PFS was 88.3%, 81.3%, and 77.0%, respectively. This was significantly improved (p=0.008) compared to patients >=18 years old (3, 5, and 10 year PFS of 67.3%, 60.9%, and 56.8%, respectively). Similarly, patients without prior RT (p=0.001), or prior chemotherapy (p=0.003), and with tumor volume <4.5cc (p=0.012) had significantly better PFS. On multivariable analysis, only prior RT impacted PFS (p=0.001, HR=3.705, CI: 1.76-7.80). CONCLUSIONS: GKRS for pilocytic astrocytoma results in excellent long term survival and good local control. GKRS may be a particularly useful minimally invasive tool for younger patients with smaller tumor volumes

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.

BACKGROUND AND PURPOSE/OBJECTIVE:The aim of this international, multicenter, retrospective matched cohort study is to directly compare the outcomes after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM) in pediatric versus adult patients. METHODS:We performed a retrospective review of patients with AVM who underwent SRS at 8 institutions participating in the International Gamma Knife Research Foundation from 1987 to 2014. Patients were categorized into pediatric (<18 years of age) and adult (≥18 years of age) cohorts and matched in a 1:1 ratio using propensity scores. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. RESULTS:=0.003). CONCLUSIONS:The outcomes after SRS for comparable AVMs in pediatric versus adult patients were not found to be appreciably different. SRS remains a reasonable treatment option for appropriately selected pediatric patients with AVM, who harbor a high cumulative lifetime hemorrhage risk. Age seems to be a poor predictor of AVM outcomes after SRS.

BACKGROUND:Stereotactic radiosurgery (SRS) is used to manage patients with Cushing disease (CD) who have failed surgical/medical management. Because many patients with recurrent/persistent CD lack an identifiable adenoma on neuroimaging, whole-sellar SRS has been increasingly used. Thus, we sought to define the outcomes of patients undergoing whole-sellar SRS. METHODS:An international, multicenter, retrospective cohort design was used to define clinical/endocrine outcomes for patients undergoing whole-sellar SRS for CD. Propensity-score matching was used to compare patients undergoing whole-sellar SRS and patients who underwent discreet adenoma-targeted SRS. RESULTS:were associated with shorter times to remission (P < 0.05). The 5-year recurrence-free survival rate was 86.0%. Decreased margin and maximum treatment doses were associated with recurrence (P < 0.05). New pituitary hormone deficiency occurred in 15 patients (22.7%). An additional 210 patients were identified who underwent adenoma-targeted SRS. There was no difference in remission rate, time to remission, recurrence-free survival or new endocrinopathy development between patients who underwent whole-sellar SRS and those who underwent discreet adenoma-targeted SRS. CONCLUSIONS:Whole-sellar GKRS is effective in controlling CD when an adenoma is not clearly defined on imaging or when an invasive adenoma is suspected at the time of initial surgery. Patients who undergo whole-sellar SRS have outcomes and rates of new pituitary hormone deficiency similar to those of patients who undergo discrete adenoma-targeted GKRS.

PURPOSE/OBJECTIVE:Recent advances in sodium brain MRI have allowed for increased signal-to-noise ratio, faster imaging, and the ability of differentiating intracellular from extracellular sodium concentration, opening a new window of opportunity for clinical application. In gliomas, there are significant alterations in sodium metabolism, including increase in the total sodium concentration and extracellular volume fraction. The purpose of this study is to assess the feasibility of using sodium MRI quantitative measurements to evaluate gliomas. METHODS:), apparent intracellular sodium concentration (aISC), and apparent total sodium concentration (aTSC). Measurements were made within the contralateral normal-appearing putamen, contralateral normal-appearing white matter (NAWM), and solid tumor regions (area of T2-FLAIR abnormality, excluding highly likely areas of edema, cysts, or necrosis). Paired samples t test were performed comparing NAWM and putamen and between NAWM and solid tumor. RESULTS:(p = 0.19). CONCLUSION/CONCLUSIONS:Quantitative sodium measurements can be done in glioma patients and also has provided further evidence that total sodium and extracellular volume fraction are increased in gliomas.