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Association between county-level socioeconomic status and the incidence of and surgical treatment for pituitary adenoma

David J. Cote, Carol Kruchko, Jill S. Barnholtz-Sloan, Gabriel Zada, Joseph L. Wiemels, and Quinn T. Ostrom

OBJECTIVE

The objective of this study was to evaluate the association between county-level socioeconomic status (SES) and the incidence of and surgical treatment for pituitary adenoma (PA).

METHODS

Using the Centers for Disease Control and Prevention’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results database, the authors identified the average annual age-adjusted incidence rates and calculated odds ratios (ORs) for surgical treatment of PA, stratified by a county-level index for SES, race/ethnicity, metropolitan status, and other confounders.

RESULTS

From 2006 to 2018, 167,121 PA cases were identified. There was no significant trend in the incidence of PA by county-level SES overall (incidence rate ratio [IRR] 0.98, 95% CI 0.96–1.00, p = 0.05, comparing highest to lowest quintile of SES). Among Asian or Pacific Islander (API; IRR 0.82, 95% CI 0.71–0.95, p = 0.007) and American Indian/Alaska Native (AIAN) participants (IRR 0.82, 95% CI 0.71–0.95, p = 0.009), the incidence of PA was statistically significantly lower with higher SES, while among Black individuals, the incidence of PA was higher with higher SES (IRR 1.10, 95% CI 1.05–1.15, p < 0.001, comparing 5th to 1st quintile of SES). Higher SES quintile was associated with surgical treatment of PA (OR 1.04, 95% CI 0.99–1.09, comparing highest to lowest quintile, p value for trend = 0.02). Males were more likely than females to undergo surgery (OR 1.50, 95% CI 1.47–1.53, p < 0.001), and Black (OR 0.89, 95% CI 0.86–0.91, p < 0.001) and AIAN individuals (OR 0.88, 95% CI 0.78–0.99, p = 0.04) were less likely to undergo surgery than White individuals, whereas API individuals were more likely to undergo surgery (OR 1.15, 95% CI 1.09–1.21, p < 0.001).

CONCLUSIONS

Higher county-level SES in the US was associated with a higher incidence of PA among Black individuals, but not among White individuals, while API and AIAN individuals had a lower PA incidence with higher SES. After multivariable adjustment, higher county-level SES was associated with surgical treatment of PA, and White and API individuals were significantly more likely to undergo surgery than Black or AIAN individuals.

In Journal of Neurosurgery Publish Before Print

Free access

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases

Stephanie K. Cheok, Cheng Yu, Jeffrey J. Feng, Robert G. Briggs, Frances Chow, Lindsay Hwang, Jason C. Ye, Frank J. Attenello, David Tran, Eric Chang, and Gabriel Zada

OBJECTIVE

Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM.

METHODS

The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90–05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses.

RESULTS

The authors’ cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non–small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans.

CONCLUSIONS

Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

In Neurosurgical Focus Volume 55 (2023): Issue 2 (Aug 2023): Update on Brain Metastases

Open access

Endoscopic endonasal approach for MRI–Negative Cushing’s microadenoma

Jeffrey J. Feng, Stephanie K. Cheok, Alexander G. Chartrain, John D. Carmichael, Mark S. Shiroishi, William J. Mack, and Gabriel Zada

A 54-year-old male with a history of diabetes mellitus type 2 for 12 years and hypertension was seen in the clinic due to poorly controlled diabetes. Inferior petrosal sinus sampling (IPSS) confirmed Cushing’s disease with primary adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma on the right. However, 3T and subsequent 7T MRI showed no visible tumor. An endoscopic transsphenoidal approach was selected to explore the pituitary gland and resect the presumed microadenoma. Tumor was identified in the lateral recess along the right medial cavernous sinus wall and gross-total resection (GTR) was performed. The normal pituitary gland was preserved, and the patient went into remission.

The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2324

In Neurosurgical Focus: Video Volume 9: Issue 1 (Jul 2023): Techniques in MRI–Negative Cushing Disease

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ChatGPT versus the neurosurgical written boards: a comparative analysis of artificial intelligence/machine learning performance on neurosurgical board–style questions

Benjamin S. Hopkins, Vincent N. Nguyen, Jonathan Dallas, Pavlos Texakalidis, Max Yang, Alex Renn, Gage Guerra, Zain Kashif, Stephanie Cheok, Gabriel Zada, and William J. Mack

In Journal of Neurosurgery Volume 139: Issue 3 (Sep 2023)

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Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis

Georgios Mantziaris, Stylianos Pikis, Tomas Chytka, Roman Liščák, Kimball Sheehan, Darrah Sheehan, Selcuk Peker, Yavuz Samanci, Shray K. Bindal, Ajay Niranjan, L. Dade Lunsford, Rupinder Kaur, Renu Madan, Manjul Tripathi, Dhiraj J. Pangal, Ben A. Strickland, Gabriel Zada, Anne-Marie Langlois, David Mathieu, Ronald E. Warnick, Samir Patel, Zayda Minier, Herwin Speckter, Zhiyuan Xu, Rithika Kormath Anand, and Jason P. Sheehan

OBJECTIVE

Radiological progression occurs in 50%–60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs.

METHODS

This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed.

RESULTS

Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55–4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6–12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = −0.8%, p > 0.99) or visual deficits (RD = −2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01).

CONCLUSIONS

SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

In Journal of Neurosurgery Volume 138: Issue 6 (Jun 2023)

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From white to blue light: evolution of endoscope-assisted intracranial tumor neurosurgery and expansion to intraaxial tumors

Jacob Ruzevick, Tyler Cardinal, Dhiraj J. Pangal, Ilaria Bove, Ben Strickland, and Gabriel Zada

OBJECTIVE

Intraoperative use of the endoscope to assist in visualization of intracranial tumor pathology has expanded with increasing surgeon experience and improved instrumentation. The authors aimed to study how advancements in endoscopic technology have affected the evolution of endoscope use, with particular focus on blue light–filter modification allowing for discrimination of fluorescent tumor tissue following 5-ALA administration.

METHODS

A retrospective analysis of patients undergoing craniotomy for tumor resection at a single institution between February 2012 and July 2021 was performed. Patients were included if the endoscope was used for diagnostic tumor cavity inspection or therapeutic assistance with tumor resection following standard craniotomy and microsurgical tumor resection, with emphasis on those cases in which blue light endoscopy was used. Medical records were queried for patient demographics, operative reports describing the use of the endoscope and extent of resection, associations with tumor pathology, and postoperative outcomes. Preoperative and postoperative MR images were reviewed for radiographic extent of resection.

RESULTS

A total of 52 patients who underwent endoscope-assisted craniotomy for tumor were included. Thirty patients (57.7%) were men and the average age was 52.6 ± 16.1 years. Standard white light endoscopes were used for assistance with tumor resection in 28 cases (53.8%) for tumors primarily located in the ventricular system, parasellar region, and cerebellopontine angle. A blue light endoscope for detection of 5-ALA fluorescence was introduced into our practice in 2014 and subsequently used for assistance with tumor resection in 24 cases (46.2%) (intraaxial: n = 22, extraaxial: n = 2). Beyond the use of the surgical microscope as the primary visualization source, the blue light endoscope was used to directly perform additional tumor resection in 19/21 cases as a result of improved fluorescence detection as compared to the surgical microscope. No complications were associated with the use of the endoscope or with additional resection performed under white or blue light visualization.

CONCLUSIONS

Endoscopic assistance to visualize intracranial tumors had previously been limited to white light, assisting mostly in the visualization of extraaxial tumors confined to intraventricular and cisternal compartments. Blue light–equipped endoscopes provide improved versatility and visualization of 5-ALA fluorescing tissue beyond the capability of the surgical microscope, thereby expanding its use into the realm of intraaxial tumor resections.

In Journal of Neurosurgery Volume 139: Issue 1 (Jul 2023)

Free access

Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients

Eric J. Lehrer, Manmeet S. Ahluwalia, Jason Gurewitz, Kenneth Bernstein, Douglas Kondziolka, Ajay Niranjan, Zhishuo Wei, L. Dade Lunsford, Kareem R. Fakhoury, Chad G. Rusthoven, David Mathieu, Claire Trudel, Timothy D. Malouff, Henry Ruiz-Garcia, Phillip Bonney, Lindsay Hwang, Cheng Yu, Gabriel Zada, Samir Patel, Christopher P. Deibert, Piero Picozzi, Andrea Franzini, Luca Attuati, Rahul N. Prasad, Raju R. Raval, Joshua D. Palmer, Cheng-Chia Lee, Huai-Che Yang, Brianna M. Jones, Sheryl Green, Jason P. Sheehan, and Daniel M. Trifiletti

OBJECTIVE

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival.

METHODS

This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non–small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required.

RESULTS

The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58–73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18–20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test).

CONCLUSIONS

TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

In Journal of Neurosurgery Volume 138: Issue 5 (May 2023)

Open access

Endoscopic endonasal approaches for reconstruction of traumatic anterior skull base fractures and associated cerebrospinal fistulas: patient series

Megha K. Sheth, Ben A. Strickland, Lawrance K. Chung, Robert G. Briggs, Martin Weiss, Bozena Wrobel, and Gabriel Zada

BACKGROUND

Post-traumatic cerebrospinal fluid (CSF) leaks of the anterior skull base may arise after traumatic brain injury (TBI). Onset of CSF rhinorrhea may be delayed after TBI and without prompt treatment may result in debilitating consequences. Operative repair of CSF leaks caused by anterior skull base fractures may be performed via open craniotomy or endoscopic endonasal approaches (EEAs). The authors’ objective was to review their institutional experience after EEA for repair of TBI-related anterior skull base defects and CSF leaks.

OBSERVATIONS

A retrospective review of prospectively collected data from a major level 1 trauma center was performed to identify patients with TBI who developed CSF rhinorrhea. Persistent or refractory post-traumatic CSF leaks and anterior skull base defects were repaired via EEA in four patients. Intrathecal fluorescein was administered before EEA in three patients (75%) to help aid identification of the fistula site(s). CSF leaks were eventually repaired in all patients, though one reoperation was required. During a mean follow-up of 8.75 months, there were no instances of recurrent CSF leakage.

LESSONS

Refractory, traumatic CSF leaks may be effectively repaired via EEA using a multilayer approach and nasoseptal flap reconstruction, thereby potentially obviating the need for additional craniotomy in the post-TBI setting.

In Journal of Neurosurgery: Case Lessons Volume 3 (2022): Issue 25 (Jun 2022)

Free access

The role of frailty in the clinical management of neurofibromatosis type 1: a mixed-effects modeling study using the Nationwide Readmissions Database

Shane Shahrestani, Nolan J. Brown, Ben A. Strickland, Joshua Bakhsheshian, Seyed Mohammadreza Ghodsi, Tasha Nasrollahi, Michela Borrelli, Julian Gendreau, Jacob J. Ruzevick, and Gabriel Zada

OBJECTIVE

Frailty embodies a state of increased medical vulnerability that is most often secondary to age-associated decline. Recent literature has highlighted the role of frailty and its association with significantly higher rates of morbidity and mortality in patients with CNS neoplasms. There is a paucity of research regarding the effects of frailty as it relates to neurocutaneous disorders, namely, neurofibromatosis type 1 (NF1). In this study, the authors evaluated the role of frailty in patients with NF1 and compared its predictive usefulness against the Elixhauser Comorbidity Index (ECI).

METHODS

Publicly available 2016–2017 data from the Nationwide Readmissions Database was used to identify patients with a diagnosis of NF1 who underwent neurosurgical resection of an intracranial tumor. Patient frailty was queried using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. ECI scores were collected in patients for quantitative measurement of comorbidities. Propensity score matching was performed for age, sex, ECI, insurance type, and median income by zip code, which yielded 60 frail and 60 nonfrail patients. Receiver operating characteristic (ROC) curves were created for complications, including mortality, nonroutine discharge, financial costs, length of stay (LOS), and readmissions while using comorbidity indices as predictor values. The area under the curve (AUC) of each ROC served as a proxy for model performance.

RESULTS

After propensity matching of the groups, frail patients had an increased mean ± SD hospital cost ($85,441.67 ± $59,201.09) compared with nonfrail patients ($49,321.77 ± $50,705.80) (p = 0.010). Similar trends were also found in LOS between frail (23.1 ± 14.2 days) and nonfrail (10.7 ± 10.5 days) patients (p = 0.0020). For each complication of interest, ROC curves revealed that frailty scores, ECI scores, and a combination of frailty+ECI were similarly accurate predictors of variables (p > 0.05). Frailty+ECI (AUC 0.929) outperformed using only ECI for the variable of increased LOS (AUC 0.833) (p = 0.013). When considering 1-year readmission, frailty (AUC 0.642) was outperformed by both models using ECI (AUC 0.725, p = 0.039) and frailty+ECI (AUC 0.734, p = 0.038).

CONCLUSIONS

These findings suggest that frailty and ECI are useful in predicting key complications, including mortality, nonroutine discharge, readmission, LOS, and higher costs in NF1 patients undergoing intracranial tumor resection. Consideration of a patient’s frailty status is pertinent to guide appropriate inpatient management as well as resource allocation and discharge planning.

In Neurosurgical Focus Volume 52 (2022): Issue 5 (May 2022): Neurocutaneous Disorders

Free access

Association between socioeconomic status and presenting characteristics and extent of disease in patients with surgically resected nonfunctioning pituitary adenoma

David J. Cote, Jacob J. Ruzevick, Keiko M. Kang, Dhiraj J. Pangal, Ilaria Bove, John D. Carmichael, Mark S. Shiroishi, Ben A. Strickland, and Gabriel Zada

OBJECTIVE

The aim of this study was to evaluate the association between zip code–level socioeconomic status (SES) and presenting characteristics and short-term clinical outcomes in patients with nonfunctioning pituitary adenoma (NFPA).

METHODS

A retrospective review of prospectively collected data from the University of Southern California Pituitary Center was conducted to identify all patients undergoing surgery for pituitary adenoma (PA) from 2000 to 2021 and included all patients with NFPA with recorded zip codes at the time of surgery. A normalized socioeconomic metric by zip code was then constructed using data from the American Community Survey estimates, which was categorized into tertiles. Multiple imputation was used for missing data, and multivariable linear and logistic regression models were constructed to estimate mean differences and multivariable-adjusted odds ratios for the association between zip code–level SES and presenting characteristics and outcomes.

RESULTS

A total of 637 patients were included in the overall analysis. Compared with patients in the lowest SES tertile, those in the highest tertile were more likely to be treated at a private (rather than safety net) hospital, and were less likely to present with headache, vision loss, and apoplexy. After multivariable adjustment for age, sex, and prior surgery, SES in the highest compared with lowest tertile was inversely associated with tumor size at diagnosis (−4.9 mm, 95% CI −7.2 to −2.6 mm, p < 0.001) and was positively associated with incidental diagnosis (multivariable-adjusted OR 1.72, 95% CI 1.02–2.91). Adjustment for hospital (private vs safety net) attenuated the observed associations, but disparities by SES remained statistically significant for tumor size. Despite substantial differences at presentation, there were no significant differences in length of stay or odds of an uncomplicated procedure by zip code–level SES. Patients from lower-SES zip codes were more likely to require postoperative steroid replacement and less likely to achieve gross-total resection.

CONCLUSIONS

In this series, lower zip code–level SES was associated with more severe disease at the time of diagnosis for NFPA patients, including larger tumor size and lower rates of incidental diagnosis. Despite these differences at presentation, no significant differences were observed in short-term postoperative complications, although patients with higher zip code–level SES had higher rates of gross-total resection.

In Journal of Neurosurgery Volume 137: Issue 6 (Dec 2022)