Faculty Bibliography

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.

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

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.

Context Cushing's disease (CD) due to ACTH-secreting pituitary tumors can be a management challenge. The outcomes of stereotactic radiosurgery (SRS) for CD are not fully defined. Objective To better understand the outcomes of SRS for CD and its role in management. Design International, multicenter, retrospective cohort analysis. Setting Ten medical centers participating in the International Gamma Knife Research Foundation (IGKRF). Patients Patients with CD with more than 6 months endocrine follow-up. Intervention SRS using Gamma Knife radiosurgery. Main Outcome Measures The primary outcome was endocrine remission. Radiologic response and adverse radiation effects were recorded. Results: A total of 278 patients (222 women, mean age: 41.4 years) met inclusion criteria for the study. Mean follow-up was 5.6 years (0.5-20.5 years). Twenty-two patients received SRS as a primary treatment for CD. Mean margin dose was 23.7 Gy. Cumulative initial biochemical remission was 80% at 10 years. Mean time to remission was 14.5 months. Recurrences occurred in 18% with an initial remission. Overall, the rate of durable endocrine remission was 64% at 10 years, and it was 68% among patients who received SRS as a primary treatment. Adverse radiation effects included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (p=0.01), while both visual (p < 0.0001) and nonvisual cranial neuropathy (p=0.02) were related to prior pituitary irradiation. Conclusion: SRS for CD is well tolerated and frequently results in initial remission. However, endocrine recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS

OBJECTIVEThe 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.METHODSThe 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).RESULTSThe 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.CONCLUSIONSDespite 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.

OBJECTIVE The incidence of brain metastases is increasing with improved systemic therapies, many of which have a limited impact on intracranial disease. Stereotactic radiosurgery (SRS) is a first-line management option for brain metastases. The purpose of this study was to determine if there is a threshold tumor size below which local control (LC) rates approach 100%, and to relate these findings to the use of routine surveillance brain imaging. METHODS From a prospective registry, 200 patients with 1237 brain metastases were identified who underwent SRS between December 2012 and May 2015. The median imaging follow-up duration was 7.9 months, and the median margin dose was 18 Gy. The maximal diameter and volume of tumors were measured. Histological analysis included 96 patients with non-small cell lung cancers (NSCLCs), 40 with melanoma, 35 with breast cancer, and 29 with other histologies. RESULTS Almost 50% of brain metastases were NSCLCs and commonly measured less than 6 mm in maximal diameter or 70 mm3 in volume. Thirty-three of 1237 tumors had local progression at a median of 8.8 months. The 1- and 2-year actuarial LC rates were 97% and 93%, respectively. LC of 100% was achieved for all intracranial metastases less than 100 mm3 in volume or 6 mm in diameter. Patients whose tumors at first SRS were less than 10 mm maximal diameter or a volume of 250 mm3 had improved overall survival. CONCLUSIONS SRS can achieve LC rates approaching 100% for subcentimeter metastases. The earlier initial detection and prompt treatment of small intracranial metastases may prevent the development of neurological symptoms and the need for resection, and improve overall survival. To identify tumors when they are small, routine surveillance brain imaging should be considered as part of the standard of care for lung, breast, and melanoma metastases. CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort; evidence: Class II.