Socioeconomic and Racial Disparities Impact Access to High Volume Centers During Meningioma Treatment.

BACKGROUND: Studies examining the relationship between hospital case volume, socioeconomic determinants of health, and patient outcomes are lacking. We sought to evaluate these associations in the surgical management of intracranial meningiomas. METHODS: We queried the National Inpatient Sample (NIS) database for patients who underwent craniotomy for the resection of meningioma in 2013. We categorized hospitals into high (HVC) or low (LVC) volume centers. We compared outcomes in 2016 to assess the potential impact of the Affordable Care Act (ACA) on healthcare equity. Primary outcome measures included hospital mortality, length of stay (LOS), complications, and disposition. RESULTS: A total of 10270 encounters were studied (LVC: n=5730 [55.8%], HVC n=4340 [44.2%]). 62.9% of LVC patients identified as white compared to 70.2% at HVC (p<0.01). A higher percentage of patients at LVC came from the lower two quartiles of median household income than HVC (49.9% vs 44.2% p<0.001). Higher mortality (1.3% vs 0.9% p = 0.041) was in LVCs. Multivariable regression analysis showed LVCs were significantly associated with increased complication (OR 1.36, 95% CI 1.30-1.426, p<0.001) and longer hospital LOS (OR -0.05, 95% CI -0.92,-0.45, p=<0.001). There was a higher proportion of white patients at HVCs in 2016 compared to 2013 (67.9% vs. 72.3%). More patients from top income quartiles (24.2% vs. 40.5%) were treated at HVC in 2016 compared to 2013. CONCLUSION: This study demonstrated notable racial and socioeconomic disparities in LVC as well as access to HVCs over time. Disparities in meningioma treatment may persistent and require further study.

Corrigendum: Grade 3 Meningioma Survival and Recurrence Outcomes in an International Multicenter Cohort.

[This corrects the article DOI: 10.1055/s-0044-1779888.].

Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Site-Specific Quality of Life Outcomes Following Anterior Skull Base Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a limited understanding of site-specific, quality of life (QOL) outcomes in anterior skull base surgery (ASBS). The objective of the present investigation was to characterize postoperative change in QOL outcomes for anterior skull base lesions following open and endoscopic surgery. METHODS: A comprehensive review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using the PubMed, Scopus, Embase, and Cochrane databases for studies reporting pre- and postoperative, site-specific, QOL outcome measures in ASBS using validated questionnaires. Studies utilizing the anterior skull base quality of life (ASBQ) questionnaire or the skull base inventory were included. Investigations focusing on skull base surgery for pituitary lesions, as well as survey validation and non-English studies, were excluded. RESULTS: A total of 112 studies were screened; 4 studies, comprising a total of 195 patients and focusing exclusively on the ASBQ, were included in the systematic review. Using a fixed effect model for the meta-analysis, the mean ASBQ score was similar at six (3.45, P = 0.312; -0.19, 95% confidence interval: -0.57, 0.18) and 12 months postoperatively (3.6, P = 0.147; 0.3, 95% confidence interval: -0.11, 0.72) compared to baseline (3.53). CONCLUSIONS: Across a variety of anterior skull base pathologies, skull base-specific QOL demonstrated no improvement at 6 months and 12 months postsurgery. Few studies to date have published pre- and postoperative QOL data for patients undergoing ASBS, highlighting a current shortcoming in the available literature. Long-term follow-up in patients undergoing open and endoscopic approaches will be necessary to better understand and optimize outcomes for patients having ASBS.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles. METHODS: The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. RESULTS: No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences. CONCLUSIONS: Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.

Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. SIGNIFICANCE: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.

The RAPID Consortium: A Platform for Clinical and Translational Pituitary Tumor Research.

Objectives Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. Design The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. Methods The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. Setting/Participants RAPID was formed by 11 academic U.S. pituitary centers. Results A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. Conclusion The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort.

OBJECTIVE: Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients. METHODS: Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022. RESULTS: A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%-77%) and 37% (95% CI 28%-48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period. CONCLUSIONS: This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

Superiorly Based Middle Turbinate Flap for Repair of Cerebrospinal Fluid Rhinorrhea: A Cadaveric Feasibility Study and Case Series.

Objectives Cerebrospinal fluid (CSF) leaks of the anterior cranial base are frequently repaired with endonasal, multilayered reconstructions. Vascularized tissue flaps are superior to free mucosal grafts and biomaterials in many cases. Limitations of previously described flaps include reach, rotation, pedicle availability, and postoperative sinonasal morbidity. The objective of this study is to describe the superiorly based middle turbinate flap, a novel vascularized mucosal reconstruction option, and to present a case series demonstrating flap utility. Design Cadaveric feasibility study with technical description and illustrative case series. Setting Tertiary medical center. Participants Three silicone-injected cadaveric specimens (6 sides); 7 patients with CSF rhinorrhea from bony dehiscence of the anterior cranial fossa repaired with a superiorly based middle turbinate flap. Outcome Measures Cadaveric feasibility, in vivo repair outcomes, sinonasal symptoms, and postoperative healing. Results Cadaveric dissection demonstrated a consistent vascular plexus arising from the anterior and posterior ethmoid arteries, originating at the superior attachment of the middle turbinate and traveling inferiorly to supply the mucosa of the middle turbinate. Mean surface area of the flap was 776.67 ± 114.60 mm 2 . The clinical series of 7 patients involved leaks around the cribriform plate and fovea ethmoidalis. There were no instances of repair failure. All cases showed rapid and complete remucosalization without significant sinonasal morbidity. Conclusion The superiorly based middle turbinate flap is a reliable, versatile, and effective option for a vascularized mucosal flap onlay that can be used in anterior skull base reconstruction. This flap is particularly useful in the repair of defects involving the cribriform plate and fovea ethmoidalis.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

An evaluation of biobanking and therapeutic clinical trial representation among adult glioma patients from rural and urban Utah.

Background: Social determinants of health (SDOHs)-specifically those related to rurality, health care accessibility, and income-may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients. Methods: We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation. We used multivariable models to evaluate SDOHs and geographic information system mapping to assess representation across Utah's counties. We utilized the most recent 10-year datasets of patients treated for glioma at HCI and from the Utah Cancer Registry to analyze survival and incidence, respectively. Results: A total of 570 participants (68 trials) resided in Utah, 84.4% from urban counties, 13.5% from rural counties, and 2.1% from frontier (least-populous) counties. Nineteen counties (65.5%) were underrepresented in trials (enrolled participants vs. eligible), 1 (3.5%) was represented in a near-1:1 ratio, and 9 (31.0%) were overrepresented. Counties with greater enrollment had greater population densities, highest per-capita income, and proximity to HCI. Among patients treated at HCI, patients from rural/frontier counties had equivalent survival with urban patients across nearly all glioma types, including glioblastomas, despite underrepresentation in clinical trials. Conclusions: By highlighting disparities in clinical trial enrollment, our results can support efforts to improve recruitment in underrepresented regions, which can assist providers in delivering equitable care for all patients.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

Systematic Review of Research, Mentorship, and Career Resources for Medical Students Pursuing Neurosurgical Training.

BACKGROUND: Medical students are important team members and future healthcare providers in neurosurgery or other medical fields. We performed a systematic review evaluating studies assessing medical student guidance, mentorship, and career development in neurosurgery. The study aimed to identify the best practices and acknowledge gaps requiring improvement. METHODS: A systematic review of 586 research studies evaluating important aspects of medical student career development in neurosurgery was performed. The studies were analyzed for evidence supporting specific strategies to foster career development. RESULTS: A total of 45 studies were identified and categorized into 8 categories: 1) medical student interest groups; 2) student fellowships and institutional programs; 3) research and observership funding; 4) medical student research and scholarship; 5) student-led interest groups; 6) student mentorship; 7) educational resources; and 8) diversity, equity, and inclusion for medical students. Studies supported the significant positive effects of career resources for medical students, which often resulted in higher publication quantities, increased interest in the field, and greater ease of matriculation into a neurosurgical residency. One central gap included limited formal opportunities at many institutions, including medical schools without neurosurgery programs. Additional gaps were an absent structure for many forms of mentorship and delayed engagement of medical students in neurosurgical training, which significantly affects career interests. The currently available resources for these aspects of career development are listed. CONCLUSIONS: These studies highlight the current endeavors to encourage medical student careers. However, ample gaps and missed opportunities were also identified. Further work at both institutional and national levels is needed to improve the current environment.

Evolution of Surgical Outcomes in Endoscopic Endonasal Resection of Craniopharyngiomas.

Introduction Wide variations exist in the management of craniopharyngiomas, including pituitary stalk preservation/sacrifice. This study examines the practice patterns over 16 years using the endoscopic endonasal approach for the resection of craniopharyngiomas and it examines the effects of stalk preservation. Methods Retrospective analysis was conducted for 66 patients who underwent endoscopic transsphenoidal surgery for resection of craniopharyngiomas. Patients were stratified into three epochs: 2005 to 2009 ( N = 20), 2010 to 2015 ( N = 23), and 2016 to 2020 ( N = 20), to examine the evolution of surgical outcomes. Subgroup analysis between stalk preservation/stalk sacrifice was conducted for rate of gross total resection, anterior pituitary function preservation, and development of new permanent diabetes insipidus. Results Gross total resection rates across the first, second, and third epochs were 20, 65, and 52%, respectively ( p = 0.042). Stalk preservation across epochs were 100, 5.9, and 52.6% ( p = 0.0001). New permanent diabetes insipidus did not significantly change across epochs (37.5, 68.4, 71.4%; p = 0.078). Preservation of normal endocrine function across epochs was 25, 0, and 23.8%; ( p = 0.001). Postoperative cerebrospinal fluid (CSF) leaks significantly decreased over time (40, 4.5, and 0%; [ p = 0.0001]). Stalk preservation group retained higher normal endocrine function (40.9 vs. 0%; p = 0.001) and less normal-preoperative to postoperative panhypopituitarism (18.4 vs. 56%; p = 0.001). Stalk sacrifice group achieved higher GTR (70.8 vs. 28%, p = 0.005). At last follow-up, there was no difference in recurrence/progression rates between the two groups. Conclusion There is a continuous evolution in the management of craniopharyngiomas. Gross total resection, higher rates of pituitary stalk and hormonal preservation, and low rates of postoperative CSF leak can be achieved with increased surgical experience.

Medical Management of Meningiomas.

Meningiomas represent the most common type of benign tumor of the extra-axial compartment. Although most meningiomas are benign World Health Organization (WHO) grade 1 lesions, the increasingly prevalent of WHO grade 2 lesion and occasional grade 3 lesions show worsened recurrence rates and morbidity. Multiple medical treatments have been evaluated but show limited efficacy. We review the status of medical management in meningiomas, highlighting successes and failures of various treatment options. We also explore newer studies evaluating the use of immunotherapy in management.