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Arman Jahangiri, Patrick M. Flanigan, Maxine Arnush, Ankush Chandra, Jonathan W. Rick, Sarah Choi, Alvin Chou, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Neurosurgeons play an important role in advancing medicine through research, the funding of which is historically linked to the National Institutes of Health (NIH). The authors defined variables associated with neurosurgical NIH funding, prevalence of funded topics by neurosurgical subspecialty, and temporal trends in NIH neurosurgical funding.

METHODS

The authors conducted a retrospective review of NIH-funded American Association of Neurological Surgeons members using NIH RePORTER (http://report.nih.gov/) for the years 1991–2015.

RESULTS

The authors followed 6515 neurosurgeons from 1991 to 2015, including 6107 (94%) non–MD-PhD physicians and 408 (6%) MD-PhDs. NIH grants were awarded to 393 (6%) neurosurgeons, with 23.2% of all first-time grants awarded to the top 5 funded institutions. The average total funded grant-years per funded neurosurgeon was 12.5 (range 1–85 grant-years). A higher percentage of MD-PhDs were NIH funded than MDs (22% [n = 91] vs 5% [n = 297], p < 0.0001). The most common grants awarded were R01 (128, 33%), K08 (69, 18%), F32 (60, 15%), M01 (50, 13%), and R21 (39, 10%). F32 and K08 recipients were 9-fold (18% vs 2%, p < 0.001) and 19-fold (38% vs 2%, p < 0.001) more likely to procure an R01 and procured R01 funding earlier in their careers (F32: 7 vs 12 years after residency, p = 0.03; K08: 9 vs 12 years, p = 0.01). Each year, the number of neurosurgeons with active grants linearly increased by 2.2 (R2 = 0.81, p < 0.001), whereas the number of total active grants run by neurosurgeons increased at nearly twice the rate (4.0 grants/year) (R2 = 0.91, p < 0.001). Of NIH-funded neurosurgical grants, 33 (9%) transitioned to funded clinical trial(s). Funded neurosurgical subspecialties included neuro-oncology (33%), functional/epilepsy (32%), cerebrovascular (17%), trauma (10%), and spine (6%). Finally, the authors modeled trends in the number of active training grants and found a linear increase in active R01s (R2 = 0.95, p < 0.001); however, both F32 (R2 = 0.36, p = 0.01) and K08 (R2 = 0.67, p < 0.001) funding had a significant parabolic rise and fall centered around 2003.

CONCLUSIONS

The authors observed an upward trend in R01s awarded to neurosurgeons during the last quarter century. However, their findings of decreased K08 and F32 training grant funding to neurosurgeons and the impact of these training grants on the ultimate success and time to success for neurosurgeons seeking R01 funding suggests that this upward trend in R01 funding for neurosurgeons will be difficult to maintain. The authors’ work underscores the importance of continued selection and mentorship of neurosurgeons capable of impacting patient care through research, including the MD-PhDs, who are noted to be more represented among NIH-funded neurosurgeons.

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Nicholas A. Butowski, John R. Bringas, Krystof S. Bankiewicz and Manish K. Aghi

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Ankush Chandra, Jacob S. Young, Cecilia Dalle Ore, Fara Dayani, Darryl Lau, Harsh Wadhwa, Jonathan W. Rick, Alan T. Nguyen, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM.

METHODS

The authors conducted a retrospective review of patients with GBM (2010–2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs.

RESULTS

Of 227 patients with GBM (median age 62 years, 37.9% females), 31 (13.7%) had Medicaid, 94 (41.4%) had Medicare, and 102 (44.9%) had private insurance. Medicaid patients had 30% higher overall hospital costs for surgery compared to non-Medicaid patients ($50,285 vs $38,779, p = 0.01). Medicaid patients had higher intensive care unit (ICU; p < 0.01), operating room (p < 0.03), imaging (p < 0.001), room and board (p < 0001), and pharmacy (p < 0.02) costs versus non-Medicaid patients. Medicaid patients had significantly longer overall and ICU lengths of stay (6.9 and 2.6 days) versus Medicare (4.0 and 1.5 days) and privately insured patients (3.9 and 1.8 days, p < 0.01). Medicaid patients had similar comorbidity rates to Medicare patients (67.8% vs 68.1%), and both groups had higher comorbidity rates than privately insured patients (37.3%, p < 0.0001). Only 67.7% of Medicaid patients had primary care providers (PCPs) versus 91.5% of Medicare and 86.3% of privately insured patients (p = 0.009) at the time of presentation. Tumor diameter at diagnosis was largest for Medicaid (4.7 cm) versus Medicare (4.1 cm) and privately insured patients (4.2 cm, p = 0.03). Preoperative (70 vs 90, p = 0.02) and postoperative (80 vs 90, p = 0.03) Karnofsky Performance Scale (KPS) scores were lowest for Medicaid versus non-Medicaid patients, while in subgroup analysis, postoperative KPS score was lowest for Medicaid patients (80, vs 90 for Medicare and 90 for private insurance; p = 0.03). Medicaid patients had significantly shorter median overall survival (10.7 months vs 12.8 months for Medicare and 15.8 months for private insurance; p = 0.02). Quality-adjusted life year (QALY) scores were 0.66 and 1.05 for Medicaid and non-Medicaid patients, respectively (p = 0.036). The incremental cost per QALY was $29,963 lower for the non-Medicaid cohort.

CONCLUSIONS

Patients with GBMs and Medicaid have higher surgical costs, longer lengths of stay, poorer survival, and lower QALY scores. This study indicates that these patients lack PCPs, have more comorbidities, and present later in the disease course with larger tumors; these factors may drive the poorer postoperative function and greater consumption of hospital resources that were identified. Given limited resources and rising healthcare costs, factors such as access to PCPs, equitable adjuvant therapy, and early screening/diagnosis of disease need to be improved in order to improve prognosis and reduce hospital costs for patients with GBM.

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Cecilia L. Dalle Ore, Stephen T. Magill, Adam J. Yen, Maryam N. Shahin, David S. Lee, Calixto-Hope G. Lucas, William C. Chen, Jennifer A. Viner, Manish K. Aghi, Philip V. Theodosopoulos, David R. Raleigh, Javier E. Villanueva-Meyer and Michael W. McDermott

OBJECTIVE

Extracranial meningioma metastases are uncommon, occurring in less than 1% of patients diagnosed with meningioma. Due to the rarity of meningioma metastases, patients are not routinely screened for distant disease. In this series, we report their experience with meningioma metastases and results of screening for metastases in select patients with recurrent meningiomas.

METHODS

All patients undergoing resection or stereotactic radiosurgery for primary or recurrent meningioma from 2009 to 2017 at a single center were retrospectively reviewed to identify patients who were diagnosed with or underwent imaging to evaluate for systemic metastases. Imaging to evaluate for metastases was performed with CT scanning of the chest, abdomen, and pelvis or whole-body PET/CT using either FDG or 68Ga-DOTA-octreotate (DOTATATE) tracers in 28 patients. Indications for imaging were symptomatic lesions concerning for metastasis or asymptomatic screening in patients with greater than 2 recurrences being evaluated for additional treatment.

RESULTS

Of 1193 patients treated for meningioma, 922 (77.3%) patients had confirmed or presumed WHO grade I tumors, 236 (19.8%) had grade II tumors, and 35 (2.9%) had grade III tumors. Mean follow-up was 4.3 years. A total of 207 patients experienced recurrences (17.4%), with a mean of 1.8 recurrences. Imaging for metastases was performed in 28 patients; 1 metastasis was grade I (3.6%), 16 were grade II (57.1%), and 11 were grade III (39.3%). Five patients (17.9%) underwent imaging because of symptomatic lesions. Of the 28 patients screened, 27 patients had prior recurrent meningioma (96.4%), with a median of 3 recurrences. On imaging, 10 patients had extracranial lesions suspicious for metastasis (35.7%). At biopsy, 8 were meningioma metastases, 1 was a nonmeningioma malignancy, and 1 patient was lost to follow-up prior to biopsy. Biopsy-confirmed metastases occurred in the liver (5), lung (3), mediastinum (1), and bone (1). The observed incidence of metastases was 0.67% (n = 8). Incidence increased to 2% of WHO grade II and 8.6% of grade III meningiomas. Using the proposed indications for screening, the number needed to screen to identify one patient with biopsy-confirmed malignancy was 3.83.

CONCLUSIONS

Systemic imaging of patients with multiply recurrent meningioma or symptoms concerning for metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision making for additional treatments.

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Stephen T. Magill, Cecilia L. Dalle Ore, Michael A. Diaz, Daara D. Jalili, David R. Raleigh, Manish K. Aghi, Philip V. Theodosopoulos and Michael W. McDermott

OBJECTIVE

Recurrent meningiomas are primarily managed with radiation therapy or repeat resection. Surgical morbidity after reoperation for recurrent meningiomas is poorly understood. Thus, the objective of this study was to report surgical outcomes after reoperation for recurrent non–skull base meningiomas.

METHODS

A retrospective review of patients was performed. Inclusion criteria were patients with recurrent meningioma who had prior resection and supratentorial non–skull base location. Univariate and multivariate logistic regression and recursive partitioning analysis were used to identify risk factors for surgical complications.

RESULTS

The authors identified 67 patients who underwent 111 reoperations for recurrent supratentorial non–skull base meningiomas. The median age was 53 years, 49% were female, and the median follow-up was 9.8 years. The most common presenting symptoms were headache, weakness, and seizure. The WHO grade after the last reoperation was grade I in 22% of cases, grade II in 51%, and grade III in 27%. The tumor grade increased at reoperation in 22% of cases. Tumors were located on the convexity (52%), parasagittal (33%), falx (31%), and multifocal (19%) locations. Tumors involved the middle third of the sagittal plane in 52% of cases. In the 111 reoperations, 48 complications occurred in 32 patients (48%). There were 26 (54%) complications requiring surgical intervention. There was no perioperative mortality. Complications included neurological deficits (14% total, 8% permanent), wound dehiscence/infection (14%), and CSF leak/pseudomeningocele/hydrocephalus (9%). Tumors that involved the middle third of the sagittal plane (OR 6.97, 95% CI 1.5–32.0, p = 0.006) and presentation with cognitive changes (OR 20.7, 95% CI 2.3–182.7, p = 0.001) were significantly associated with complication occurrence on multivariate analysis. The median survival after the first reoperation was 11.5 years, and the 2-, 5-, and 10-year Kaplan-Meier survival rates were 91.0%, 68.8%, and 50.0%, respectively.

CONCLUSIONS

Reoperation for recurrent supratentorial non–skull base meningioma is associated with a high rate of complications. Patients with cognitive changes and tumors that overlap the middle third of the sagittal plane are at increased risk of complications. Nevertheless, excellent long-term survival can be achieved without perioperative mortality.

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Jonathan Rick, Arman Jahangiri, Patrick M. Flanigan, Ankush Chandra, Sandeep Kunwar, Lewis Blevins and Manish K. Aghi

OBJECTIVE

Acromegaly results in disfiguring growth and numerous medical complications. This disease is typically caused by growth hormone (GH)–secreting pituitary adenomas, which are treated first by resection, followed by radiation and/or medical therapy if needed. A subset of acromegalics have dual-staining pituitary adenomas (DSPAs), which stain for GH and prolactin. Presentations and treatment outcomes for acromegalics with DSPAs are not well understood.

METHODS

The authors retrospectively reviewed the records of more than 5 years of pituitary adenomas resected at their institution. Data were collected on variables related to clinical presentation, tumor pathology, radiological size, and disease recurrence. The Fisher’s exact test, ANOVA, Student t-test, chi-square test, and Cox proportional hazards and multiple logistic regression were used to measure statistical significance.

RESULTS

Of 593 patients with pituitary adenoma, 91 presented with acromegaly. Of these 91 patients, 69 (76%) had tumors that stained for GH only (single-staining somatotrophic adenomas [SSAs]), while 22 (24%) had tumors that stained for GH and prolactin (DSPAs). Patients with DSPAs were more likely to present with decreased libido (p = 0.012), signs of acromegalic growth (p = 0.0001), hyperhidrosis (p = 0.0001), and headaches (p = 0.043) than patients with SSAs. DSPAs presented with significantly higher serum prolactin (60.7 vs 10.0 µg/L, p = 0.0002) and insulin-like growth factor-1 (IGF-1) (803.6 vs 480.0 ng/ml, p = 0.0001), and were more likely to have IGF-1 levels > 650 ng/ml (n = 13 [81.3%] vs n = 6 [21.4%], p = 0.0001) than patients with SSAs despite similar sizes (1.8 vs 1.7 cm, p = 0.5). Patients with DSPAs under 35 years of age were more likely to have a recurrence (n = 4 [50.0%] vs n = 3 [11.1%], p = 0.01) than patients with SSAs under the age of 35. DSPA patients were less likely to achieve remission with surgery than SSA patients (n = 2 [20%] vs n = 19 [68%], p = 0.01). Univariate analysis identified single-staining tumors (p = 0.02), gross-total resection (p = 0.02), and tumor diameter (p = 0.05) as predictors of surgical remission. Multiple logistic regression demonstrated that SSAs (p = 0.04) were independently associated with surgical remission of acromegaly. Kaplan-Meier analysis revealed that DSPAs had more time until disease remission (p = 0.033).

CONCLUSIONS

Acromegalics with tumors that stain for prolactin and GH, which represented almost a quarter of acromegalics in this cohort, had more aggressive clinical presentations and postoperative outcomes than SSAs. Prolactin staining provides useful information for acromegalics undergoing pituitary surgery.

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Lauren E. Rotman, T. Brooks Vaughan, James R. Hackney and Kristen O. Riley

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Michael M. Safaee, Ramin A. Morshed, Jordan Spatz, Sujatha Sankaran, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Interfacility neurosurgical transfers to tertiary care centers are driven by a number of variables, including lack of on-site coverage, limited available technology, insurance factors, and patient preference. The authors sought to assess the timing and necessity of surgery and compared transfers to their institution from emergency departments (ED) and inpatient units at other hospitals.

METHODS

Adult neurosurgical patients who were transferred to a single tertiary care center were analyzed over 12 months. Patients with traumatic injuries or those referred from skilled nursing facilities or rehabilitation centers were excluded.

RESULTS

A total of 504 transferred patients were included, with mean age 55 years (range 19–92 years); 53% of patients were women. Points of origin were ED in 54% cases and inpatient hospital unit in 46%, with a mean distance traveled for most patients of 119 miles. Broad diagnosis categories included brain tumors (n = 142, 28%), vascular lesions, including spontaneous and hypertensive intracerebral hemorrhage (n = 143, 28%), spinal lesions (n = 126, 25%), hydrocephalus (n = 45, 9%), wound complications (n = 29, 6%), and others (n = 19, 4%). Patients transferred from inpatient units had higher rates of surgical intervention (75% vs 57%, p < 0.001), whereas patients transferred from the ED had higher rates of urgent surgery (20% vs 8%, p < 0.001) and shorter mean time to surgery (3 vs 5 days, p < 0.001). Misdiagnosis rates were higher among ED referrals (11% vs 4%, p = 0.008). Across the same timeframe, patients undergoing elective admission (n = 1986) or admission from the authors’ own ED (n = 248) had significantly shorter lengths of stay (p < 0.001) and ICU days (p < 0.001) than transferred patients, as well as a significantly lower total cost ($44,412, $46,163, and $72,175, respectively; p < 0.001).

CONCLUSIONS

The authors present their 12-month experience from a single tertiary care center without Level I trauma designation. In this cohort, 65% of patients required surgery, but the rates were higher among inpatient referrals, and misdiagnosis rates were higher among ED transfers. These data suggest that admitting nonemergency patients to local hospitals may improve diagnostic accuracy of patients requiring urgent care, more precisely identify patients in need of transfer, and reduce costs. Referring facilities may lack necessary resources or expertise, and the Emergency Medical Treatment and Active Labor Act (EMTALA) obligates tertiary care centers to accept these patients under those circumstances. Telemedicine and integration of electronic medical records may help guide referring hospitals to pursue additional workup, which may eliminate the need for unnecessary transfer and provide additional cost savings.

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Ankush Chandra, Jonathan W. Rick, Cecilia Dalle Ore, Darryl Lau, Alan T. Nguyen, Diego Carrera, Alexander Bonte, Annette M. Molinaro, Philip V. Theodosopoulos, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Glioblastoma (GBM) is an aggressive brain malignancy with a short overall patient survival, yet there remains significant heterogeneity in outcomes. Although access to health care has previously been linked to impact on prognosis in several malignancies, this question remains incompletely answered in GBM.

METHODS

This study was a retrospective analysis of 354 newly diagnosed patients with GBM who underwent first resection at the authors’ institution (2007–2015).

RESULTS

Of the 354 patients (median age 61 years, and 37.6% were females), 32 (9.0%) had no insurance, whereas 322 (91.0%) had insurance, of whom 131 (40.7%) had Medicare, 45 (14%) had Medicaid, and 146 (45.3%) had private insurance. On average, insured patients survived almost 2-fold longer (p < 0.0001) than those who were uninsured, whereas differences between specific insurance types did not influence survival. The adjusted hazard ratio (HR) for death was higher in uninsured patients (HR 2.27 [95% CI 1.49–3.33], p = 0.0003). Age, mean household income, tumor size at diagnosis, and extent of resection did not differ between insured and uninsured patients, but there was a disparity in primary care physician (PCP) status—none of the uninsured patients had PCPs, whereas 72% of insured patients had PCPs. Postoperative adjuvant treatment rates with temozolomide (TMZ) and radiation therapy (XRT) were significantly less in uninsured (TMZ in 56.3%, XRT in 56.3%) than in insured (TMZ in 75.2%, XRT in 79.2%; p = 0.02 and p = 0.003) patients. Insured patients receiving both agents had better prognosis than uninsured patients receiving the same treatment (9.1 vs 16.34 months; p = 0.025), suggesting that the survival effect in insured patients could only partly be explained by higher treatment rates. Moreover, having a PCP increased survival among the insured cohort (10.7 vs 16.1 months, HR 1.65 [95% CI 1.27–2.15]; p = 0.0001), which could be explained by significant differences in tumor diameter at initial diagnosis between patients with and without PCPs (4.3 vs 4.8 cm, p = 0.003), and a higher rate of clinical trial enrollment, suggesting a critical role of PCPs for a timelier diagnosis of GBM and proactive cancer care management.

CONCLUSIONS

Access to health care is a strong determinant of prognosis in newly diagnosed patients with GBM. Any type of insurance coverage and having a PCP improved prognosis in this patient cohort. Higher rates of treatment with TMZ plus XRT, clinical trial enrollment, fewer comorbidities, and early diagnosis may explain survival disparities. Lack of health insurance or a PCP are major challenges within the health care system, which, if improved upon, could favorably impact the prognosis of patients with GBM.

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Fara Dayani, Jacob S. Young, Alexander Bonte, Edward F. Chang, Philip Theodosopoulos, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Butterfly glioblastoma (bGBM) is a rare type of GBM, characterized by a butterfly pattern on MRI studies because of its bihemispheric involvement and invasion of the corpus callosum (CC). There is a profound gap in the knowledge regarding the optimal treatment approach as well as the safety and survival benefits of resection in treating this aggressive brain tumor. In this retrospective study, authors add to our understanding of these tumors by identifying the clinical characteristics and outcomes of patients with bGBM.

METHODS

An institutional database was reviewed for GBM cases treated in the period from 2004 to 2014. Records were reviewed to identify adult patients with bGBM. Cases of GBM with invasion of the CC without involvement of the contralateral hemisphere and bilateral GBMs without involvement of the CC were excluded from the study. Patient and tumor characteristics were gleaned from the medical records, and volumetric analysis was performed using T1-weighted MRI studies.

RESULTS

From among 1746 cases of GBM, 39 cases of bGBM were identified. Patients had a mean age of 57.8 years at diagnosis. Headache and confusion were the most common presenting symptoms (48.7% and 33.3%, respectively). The median overall survival was 3.2 months from diagnosis with an overall 6-month survival rate of 38.1%. Age, Karnofsky Performance Status at diagnosis, preoperative tumor volume, postoperative tumor volume, and extent of resection were found to significantly impact survival in the univariate analysis. On multivariate analysis, preoperative tumor volume and treatment approach of resection versus biopsy were identified as independent prognostic factors regardless of the patient-specific characteristics of age and KPS at diagnosis. Resection and biopsy were performed in 35.9% and 64.1% of patients, respectively. Resection was found to confer a better prognosis than biopsy (HR 0.37, p = 0.009) with a minimum extent of resection of 86% to observe survival benefits (HR 0.054, p = 0.03). The rate of persistent neurological deficits from resection was 7.14%. Patients younger than 70 years had a better prognosis (HR 0.32, p = 0.003). Patients undergoing resection and receiving adjuvant chemoradiation had a better prognosis than patients who lacked one of the three treatment modalities (HR = 0.34, p = 0.015).

CONCLUSIONS

Resection of bGBM is associated with low persistent neurological deficits, with improvement in survival compared to biopsy. A more aggressive treatment approach involving aggressive resection and adjuvant chemoradiation has significant survival benefits and improves outcome.