Faculty Bibliography

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: 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

BACKGROUND:Hearing preservation is a goal for many patients with vestibular schwannoma. We examined pretreatment magnetic resonance imaging (MRI) and posttreatment hearing outcome after stereotactic radiosurgery. METHODS:From 2004 to 2014, a cohort of 125 consecutive patients with vestibular schwannoma (VS) treated via stereotactic radiosurgery (SRS) were retrospectively reviewed. MRIs containing three-dimensional constructive interference in steady state or equivalent within 1 year before treatment were classified by two radiologists for pretreatment characteristics. "Good" hearing was defined as American Academy of Otolaryngology-Head and Neck Surgery class A. Poor hearing outcome was defined as loss of good pretreatment hearing after stereotactic radiosurgery. RESULTS:Sixty-one patients met criteria for inclusion. Most had tumors in the distal internal auditory canal (55%), separated from the brainstem (63%), oval shape (64%) without cysts (86%), and median volume of 0.85 ± 0.55 cm. Pretreatment audiograms were performed a median of 108 ± 173 days before stereotactic radiosurgery; 38% had good pretreatment hearing. Smaller tumor volume (p < 0.005) was the only variable associated with good pretreatment hearing. 49 (80%) patients had posttreatment audiometry, with median follow-up of 197 ± 247 days. Asymmetrically decreased pretreatment cochlear CISS signal on the side of the VS was the only variable associated with poor hearing outcome (p = 0.001). Inter-rater agreement on cochlear three-dimensional constructive interference in steady state preservation was 91%. CONCLUSIONS:Decreased cochlear CISS signal may indicate a tumor's association with the cochlear neurovascular bundle, influencing endolymph protein concentration and creating an inability to preserve hearing. This important MRI characteristic can influence planning, counseling, and patient selection for vestibular schwannoma treatment.

The use of "big data" in neurosurgical research has become increasingly popular. However, using this type of data comes with limitations. This study aimed to shed light on this new approach to clinical research. We compiled a list of commonly used databases that were not specifically created to study neurosurgical procedures, conditions, or diseases. Three North American journals were manually searched for articles published since 2000 utilizing these and other non-neurosurgery-specific databases. A number of data points per article were collected, tallied, and analyzed.A total of 324 articles were identified since 2000 with an exponential increase since 2011 (257/324, 79%). The Journal of Neurosurgery Publishing Group published the greatest total number (n = 200). The National Inpatient Sample was the most commonly used database (n = 136). The average study size was 114,841 subjects (range, 30-4146,777). The most prevalent topics were vascular (n = 77) and neuro-oncology (n = 66). When categorizing study objective (recognizing that many papers reported more than 1 type of study objective), "Outcomes" was the most common (n = 154). The top 10 institutions by primary or senior author accounted for 45%-50% of all publications. Harvard Medical School was the top institution, using this research technique with 59 representations (31 by primary author and 28 by senior).The increasing use of data from non-neurosurgery-specific databases presents a unique challenge to the interpretation and application of the study conclusions. The limitations of these studies must be more strongly considered in designing and interpreting these studies.

BACKGROUND: Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus >/=5 brain metastases treated with radiosurgery. METHODS: We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with >/=5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. RESULTS: On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P<0.001). Patients with 1 to 4 metastases had a median OS of 10.8 months (95% confidence interval, 6.1-15.6 mo), compared with a median OS of 8.5 months (95% confidence interval, 4.4-12.6 mo) for patients with >/=5 metastases (P=0.143). The actuarial 6 month local failure rate was 5% for patients with 1 to 4 metastases versus 3.2% for patients with >/=5 metastases (P=0.404). There was a significant difference in systemic disease status between the 2 groups; 30% of patients had controlled systemic disease in the <5 lesions group, versus 8% controlled systemic disease in the >/=5 lesions group (P=0.005). Patients with 1 to 4 metastases did not have significantly improved OS in a multivariable model adjusting for systemic disease status, systemic extracranial metastases, and other key variables. The Chi-squared Automated Interaction Detection tree (machine learning technique) algorithm consistently identified performance status and systemic disease status as key to disease classification, but not intracranial metastases. CONCLUSIONS: Although the number of brain metastases has previously been accepted as an independent prognostic indicator, our multicenter analysis demonstrates that the number of intracranial metastases is highly correlated with overall disease burden and clinical status. Proper matching and controlling for these other determinants of survival demonstrates that the number of intracranial metastases alone is not an independent predictive factor, but rather a surrogate for other clinical factors.

OBJECTIVE The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiological conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both of which may contribute to ocular dysmotility. The purpose of this study was to assess the impact of elevated ICP on eye-tracking performed while patients were watching a short film clip. METHODS Awake patients requiring placement of an ICP monitor for clinical purposes underwent eye tracking while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye-tracking metrics with changes in ICP. RESULTS Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in 23 patients (12 women, 11 men, mean age 46.8 years) on 55 separate occasions. Eye-tracking measures correlating with CN function linearly decreased with increasing ICP (p < 0.001). Measures for CN VI were most prominently affected. The area under the curve (AUC) for eye-tracking metrics to discriminate between ICP < 12 and >/= 12 mm Hg was 0.798. To discriminate an ICP < 15 from >/= 15 mm Hg the AUC was 0.833, and to discriminate ICP < 20 from >/= 20 mm Hg the AUC was 0.889. CONCLUSIONS Increasingly elevated ICP was associated with increasingly abnormal eye tracking detected while patients were watching a short film clip. These results suggest that eye tracking may be used as a noninvasive, automatable means to quantitate the physiological impact of elevated ICP, which has clinical application for assessment of shunt malfunction, pseudotumor cerebri, concussion, and prevention of second-impact syndrome.

OBJECTIVE Approximately 75%-92% of patients with trigeminal neuralgia (TN) achieve pain relief after Gamma Knife surgery (GKS), although a proportion of these patients will experience recurrence of their pain. To evaluate the reasons for durability or recurrence, this study determined the impact of trigeminal nerve length and volume, the nerve dose-volume relationship, and the presence of neurovascular compression (NVC) on pain outcomes after GKS for TN. METHODS Fifty-eight patients with 60 symptomatic nerves underwent GKS for TN between 2013 and 2015, including 15 symptomatic nerves secondary to multiple sclerosis (MS). High-resolution MRI was acquired the day of GKS. The median maximum dose was 80 Gy for initial GKS and 65 Gy for repeat GKS. NVC, length and volume of the trigeminal nerve within the subarachnoid space of the posterior fossa, and the ratio of dose to nerve volume were assessed as predictors of recurrence. RESULTS Follow-up was available on 55 patients. Forty-nine patients (89.1%) reported pain relief (Barrow Neurological Institute [BNI] Grades I-IIIb) after GKS at a median duration of 1.9 months. The probability of maintaining pain relief (BNI Grades I-IIIb) without requiring resumption or an increase in medication was 93% at 1 year and 84% at 2 years for patients without MS, and 68% at 1 year and 51% at 2 years for all patients. The nerve length, nerve volume, target distance from the brainstem, and presence of NVC were not predictive of pain recurrence. Patients with a smaller volume of nerve (< 35% of the total nerve volume) that received a high dose (>/= 80% isodose) were less likely to experience recurrence of their TN pain after 1 year (mean time to recurrence: < 35%, 32.2 +/- 4.0 months; > 35%, 17.9 +/- 2.8 months, log-rank test, chi2 = 4.3, p = 0.039). CONCLUSIONS The ratio of dose to nerve volume may predict recurrence of TN pain after GKS. Prospective studies are needed to determine the optimal dose to nerve volume ratio and whether this will result in longer pain-free outcomes.