Faculty Bibliography

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

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.

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.

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.

Stereotactic radiosurgery has revolutionized the management of brain metastases. It delivers focused, highly conformal, ionizing radiation to a tumor delineated using high-resolution imaging, with low toxicity to adjacent brain structures. Randomized controlled and prospective trials have demonstrated a survival advantage and high local control rates after stereotactic radiosurgery for metastatic disease to the central nervous system, including for up to 10 brain metastases. Its minimal-access nature makes it an attractive alternative to surgical resection. Furthermore, in addition to chemotherapy, newer targeted therapies and immunotherapies with improved side-effect profiles allow for the concurrent delivery of systemic therapy with radiosurgery, with possible additive or synergistic effects, expediting the treatment of both extracranial and intracranial disease. The modern management of brain metastasis patients should include consideration of routine staging and surveillance magnetic resonance imaging scans in patients with higher-stage cancer to detect intracranial metastases earlier and treat promptly with radiosurgery in order to prevent the development of neurologic symptoms and the need for surgical resection.

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.

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.

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.