Faculty Bibliography

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.

OBJECTIVE For some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors. METHODS Nine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5-144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm3 (range 0.8-22.6 cm3), and the median margin dose was 12.5 Gy (range 10-18 Gy). Patients with neurofibromatosis were excluded from this study. RESULTS The median follow-up was 51 months (range 6-266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm3 (p = 0.037) and non-dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5-38 months). Six patients underwent repeat SRS at a median of 64 months (range 44-134 months). Four patients underwent resection at a median of 14 months after SRS (range 8-30 months). CONCLUSIONS Stereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early ( 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

OBJECTIVE Meningiomas are the most common benign extramedullary lesions of the foramen magnum; however, their optimal management remains undefined. Given their location, foramen magnum meningiomas (FMMs) can cause significant morbidity, and complete microsurgical removal can be challenging. Anterior and anterolateral FMMs carry greater risks with surgery, but they comprise the majority of these lesions. As an alternative to resection, stereotactic radiosurgery (SRS) has been used to treat FMMs in small case series. To more clearly define the outcomes of SRS and to delineate a rational management paradigm for these lesions, the authors analyzed the safety and efficacy of SRS for FMM in an international multicenter trial. METHODS Seven medical centers participating in the International Gamma Knife Research Foundation (IGKRF) provided data for this retrospective cohort study. Patients who were treated with Gamma Knife radiosurgery and whose clinical and radiological follow-up was longer than 6 months were eligible for study inclusion. Data from pre- and post-SRS radiological and clinical evaluations were analyzed. Stereotactic radiosurgery treatment variables were recorded. RESULTS Fifty-seven patients (39 females and 18 males, with a median age of 64 years) met the study inclusion criteria. Thirty-two percent had undergone prior microsurgical resection. Patients most frequently presented with cranial neuropathy (39%), headache (35%), numbness (32%), and ataxia (30%). Median pre-SRS tumor volume was 2.9 cm3. Median SRS margin dose was 12.5 Gy (range 10-16 Gy). At the last follow-up after SRS, 49% of tumors were stable, 44% had regressed, and 7% had progressed. Progression-free survival rates at 5 and 10 years were each 92%. A greater margin dose was associated with a significantly increased likelihood of tumor regression, with 53% of tumors treated with > 12 Gy regressing. Fifty-two percent of symptomatic patients noted some clinical improvement. Adverse radiation effects were limited to hearing loss and numbness in 1 patient (2%). CONCLUSIONS Stereotactic radiosurgery for FMM frequently results in tumor control or tumor regression, as well as symptom improvement. Margin doses > 12 Gy were associated with increased rates of tumor regression. Stereotactic radiosurgery was generally safe and well tolerated. Given its risk-benefit profile, SRS may be particularly useful in the management of small- to moderate-volume anterior and anterolateral FMMs.

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.

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: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.

BACKGROUND:Early encounters with palliative care (PC) can influence health-care utilization, clinical outcome, and cost. AIM/OBJECTIVE:To study the effect of timing of PC encounters on brain metastasis patients at an academic medical center. SETTING/PARTICIPANTS/METHODS:All patients diagnosed with brain metastases from January 2013 to August 2015 at a single institution with inpatient and/or outpatient PC records available for review (N = 145). DESIGN/METHODS:Early PC was defined as having a PC encounter within 8 weeks of diagnosis with brain metastases; late PC was defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts of early (n = 46) and late (n = 46) PC patients were compared to control for differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis. Details of the palliative encounter, patient outcomes, and health-care utilization were collected. RESULTS:Early PC versus late PC patients had no differences in baseline KPS, age, or gender. Early PC patients had significantly fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8 vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following inpatient admissions, early PC patients were more likely to be discharged home (59% vs 35%; P = .04). CONCLUSIONS:Timely PC consultations are advisable in this patient population and can reduce health-care utilization.

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.

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.