Faculty Bibliography

OBJECTIVE:Stereotactic radiosurgery (SRS) is increasingly used for the treatment of brain metastasis. To date, most studies have focused on survival, radiological response, or surrogate quality endpoints such as Karnofsky Performance Scale status or neurocognitive indices. The current study prospectively evaluated pre-procedural factors impacting quality of life in brain metastasis patients undergoing SRS. METHODS:Using a national, cloud-based platform, patients undergoing SRS for brain metastasis were accrued to the registry. Quality of life prior to SRS was assessed using the 5-level EQ-5D (EQ5D-L) validated tool; additionally, patient and treatment attributes were collected. Patient quality of life was assessed as part of routine follow-up after SRS. Factors predicting a difference in the aggregate EQ5D-L score or the subscores were evaluated. Pre-SRS covariates impacting changes in EQ5D-L were statistically evaluated. Statistical analyses were conducted using multivariate linear regression models. RESULTS:EQ5D-L results were available for 116 patients. EQ5D-L improvement (average of 0.387) was noted in patients treated with earlier SRS (p = 0.000175). Worsening overall EQ5D-L (average of 0.052 per lesion) was associated with an increased number of brain metastases at the time of initial presentation (p = 0.0399). Male sex predicted a risk of worsening (average of 0.347) of the pain and discomfort subscore at last follow-up (p = 0.004205). Baseline subscores of pain/discomfort were not correlated with pain/discomfort subscores at follow-up (p = 0.604), whereas baseline subscores of anxiety/depression were strongly positively correlated with the anxiety/depression follow-up subscores (p = 0.0039). CONCLUSIONS:After SRS, quality of life was likely to improve in patients treated early with SRS and worsen in those with a greater number of brain metastases. Sex differences appear to exist regarding pain and discomfort worsening after SRS. Those with high levels of anxiety and depression at SRS may benefit from medical treatment as this particular quality of life factor generally remains unchanged after SRS.

OBJECTIVE:The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke. METHODS:This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance. RESULTS:A total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4-10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, -2.1 (95% CI -3.3 to -1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9-29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0-16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1-2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (-0.735, p < 0.01) scores at 24 months. CONCLUSIONS:In this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.Clinical trial registration no.: NCT01287936 (clinicaltrials.gov).

OBJECTIVE:Given rising scrutiny of healthcare expenditures, understanding intervention costs is increasingly important. This study aimed to compare and characterize costs for vestibular schwannoma (VS) management with microsurgery and radiosurgery to inform practice decisions and appraise cost reduction strategies. METHODS:In conjunction with medical records, internal hospital financial data were used to evaluate costs. Total cost was divided into index costs (costs from arrival through discharge for initial intervention) and follow-up costs (through 36 months) for 317 patients with unilateral VSs undergoing initial management between June 2011 and December 2015. A retrospective matched cohort based on tumor size with 176 patients (88 undergoing each intervention) was created to objectively compare costs between microsurgery and radiosurgery. The full sample of 203 patients treated with resection and 114 patients who underwent radiosurgery was used to evaluate a broad range of outcomes and identify cost contributors within each intervention group. RESULTS:Within the matched cohort, average index costs were significantly higher for microsurgery (100% by definition, because costs are presented as a percentage of the average index cost for the matched microsurgery group; 95% CI 93-107) compared to radiosurgery (38%, 95% CI 38-39). Microsurgery had higher average follow-up costs (1.6% per month, 95% CI 0.8%-2.4%) compared to radiosurgery (0.5% per month, 95% CI 0.4%-0.7%), largely due to costs incurred in the initial months after resection. A major contributor to total cost and cost variability for both resection and radiosurgery was the need for additional interventions in the follow-up period, which were necessary due to complications or persistent functional deficits. Although tumor size was not associated with increased total costs for radiosurgery, linear regression analysis demonstrated that, for patients who underwent microsurgery, each centimeter increase in tumor maximum diameter resulted in an estimated increase in total cost of 50.2% of the average index cost of microsurgery (95% CI 34.6%-65.7%) (p < 0.001, R2 = 0.17). There were no cost differences associated with the proportion of inpatient days in the ICU or with specific surgical approach for patients who underwent resection. CONCLUSIONS:This study is the largest assessment to date based on internal cost data comparing VS management with microsurgery and radiosurgery. Both index and follow-up costs are significantly higher when tumors were managed with resection compared to radiosurgery. Larger tumors were associated with increased resection costs, highlighting the incremental costs associated with observation as the initial management.

OBJECTIVE:To analyze the role of industry sponsorship of randomized controlled trials (RCTs) published exclusively in 3 major North American neurosurgical journals. METHODS:Our primary objective was to determine whether an association exists between study conclusion(s) in favor of industry sponsored drugs, devices/implants, or surgical techniques and industry sponsorship. The secondary objective was to describe the quality/quantity of these neurosurgical RCTs. RESULTS:A total of 110 RCTs were analyzed, the majority were published in the Journal of Neurosurgery (85%) and were international in origin (55%). The most common subspecialty was spine (n = 29) and drug study was the most common type (n = 49). Overall quality was good with median Jadad and Detsky scores of 4 (range, 1-5) and 18 (range, 8-21), respectively. There was a statistically significant difference in RCTs with industry funding (31/40, 78%) versus those without (9/70, 13%) that published a favorable conclusion of the new drug, device/implant, or surgical technique (odds ratio [OR], 23.35; P < .0001). Multiple binomial logistic regression analysis identified "number of authors" as mildly protective (OR, 0.79; 95% confidence interval, 0.69-0.91; P = .001) and "industry funding" strongly predictive (OR, 12.34; 95% confidence interval, 2.97-51.29; P = .001) of a positive trial. CONCLUSION/CONCLUSIONS:Industry funding was associated with a much greater chance of positive findings in RCTs published in neurosurgical journals. Further efforts are needed to define the relationship between the authors and financial sponsors of neurosurgical research and explore the reasons for this finding.

OBJECTIVE It is common for a medical disorder to be managed or researched by individuals who work within different specialties. It is known that both neurosurgeons and neurotologists manage vestibular schwannoma (VS) patients. While overlap in specialty focus has the potential to stimulate multidisciplinary collaboration and innovative thinking, there is a risk of specialties forming closed-communication loops, called knowledge silos, which may inhibit knowledge diffusion. This study quantitatively assessed knowledge sharing between neurosurgery and otolaryngology on the subject of VS. METHODS A broad Web of Science search was used to download details for 4439 articles related to VS through 2016. The publishing journal's specialty and the authors' specialties (based on author department) were determined for available articles. All 114,647 of the article references were categorized by journal specialty. The prevalence of several VS topics was assessed using keyword searches of titles. RESULTS For articles written by neurosurgeons, 44.0% of citations were from neurosurgery journal articles and 23.4% were from otolaryngology journals. The citations of otolaryngology authors included 11.6% neurosurgery journals and 56.5% otolaryngology journals. Both author specialty and journal specialty led to more citations of the same specialty, though author specialty had the largest effect. Comparing the specialties' literature, several VS topics had significantly different levels of coverage, including radiosurgery and hearing topics. Despite the availability of the Internet, there has been no change in the proportions of references for either specialty since 1997 (the year PubMed became publicly available). CONCLUSIONS Partial knowledge silos are observed between neurosurgery and otolaryngology on the topic of VS, based on the peer-reviewed literature. The increase in access provided by the Internet and searchable online databases has not decreased specialty reference bias. These findings offer lessons to improve cross-specialty collaboration, physician learning, and consensus building.

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.