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1.
J Neurosurg Spine ; : 1-10, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213662

RESUMO

OBJECTIVE: Neighborhood-level resource disadvantage has been previously shown to predict extent of resection, oncological follow-up, adjuvant treatment, and clinical trial participation for malignancies, including glioblastoma. The authors aimed to characterize the association between neighborhood disadvantage and long-term outcomes after spine tumor surgery. METHODS: The authors analyzed all patients who underwent surgery for primary or secondary (all metastatic pathologies) spine tumors at a single spinal oncology specialty center in the United States from 2015 to 2022. The Area Deprivation Index (ADI), a validated metric compositing 17 social determinants of health variables that ranges continuously from 0% (higher advantage) to 100% (higher disadvantage), was used to quantify neighborhood disadvantage. Patient addresses were matched to ADI on the basis of the census block of residence. Subsequently, the study population was dichotomized into advantaged (ADI 0%-33%) and disadvantaged (ADI 34%-100%) cohorts. The primary endpoint was functional status, as defined by Eastern Cooperative Oncology Group (ECOG) Performance Status Scale grade, with secondary endpoints including inpatient outcomes, mortality, readmissions, reoperations, and clinical research participation. Multivariable logistic, gamma log-link, and Cox regression adjusted for 14 confounders, including patient and oncological characteristics, general and tumor-related presenting severity, and treatment. RESULTS: In total, 237 patients underwent spine tumor surgery from 2015 to 2022, with an average age of 53.9 years, and 57.0% had primary tumors whereas 43.0% had secondary tumors; 55.3% (n = 131) were classified by ADI into the disadvantaged cohort. This cohort had higher rates of ambulation deficits on presentation (39.1% vs 23.5%, p = 0.015) and nonelective surgery (35.1% vs 23.6%, p = 0.030). Postoperatively, disadvantaged patients exhibited higher odds of residual tumor (OR 2.55, p = 0.026), especially for secondary tumors (OR 4.92, p = 0.045). Patients from disadvantaged neighborhoods additionally exhibited significantly higher odds of poor functional status at follow-up (OR 3.94, p = 0.002). Postoperative survival was 74.7% (mean follow-up 17.6 months), with the disadvantaged cohort experiencing significantly shorter survival (HR 1.92, p = 0.049). Moreover, this population had higher odds of readmission (OR 1.92, p = 0.046) and, for primary tumors, reoperation (OR 9.26, p = 0.005). Elective participation in prospective clinical research was lower among the disadvantaged cohort (OR 0.45, p = 0.016). CONCLUSIONS: Neighborhood disadvantage predicts higher rates of residual tumor, readmission, and reoperation, as well as poorer functional status, shorter postoperative survival, and decreased elective research participation. The ADI may be used to risk stratify spine oncology patients and guide targeted interventions to ameliorate neurosurgical disparities and to reduce barriers to research participation.

2.
J Neurosurg Spine ; : 1-12, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213677

RESUMO

OBJECTIVE: Earlier research has demonstrated that social determinants of health (SDoH) impact neurosurgical access and outcomes, but these trends are less characterized for spine tumors relative to intracranial tumors. The authors aimed to elucidate the association between SDoH and outcomes for a nationwide cohort of spine tumor surgery admissions. METHODS: The authors identified all admissions with a spine tumor diagnosis in the National Inpatient Sample (NIS) from 2002 to 2019. Four SDoH were analyzed: race and ethnicity, insurance, household income, and safety-net hospital (SNH) treatment. Hospitals in the top quartile of safety-net burden (in terms of percentage of patients receiving Medicaid or uninsured) were categorized as SNHs. Multivariable regression queried the association between 22 variables and 5 perioperative outcomes: mortality, discharge disposition, complications, length of stay (LOS), and hospitalization costs. Interaction term analysis with hospitalization year was used to assess longitudinal changes in outcome disparities. Finally, the authors constructed random forest machine learning models to assess the impact of SDoH variables on prognostic accuracy and to quantify the relative importance of predictors for disposition. RESULTS: Of 6,593,392 total admissions with spine tumors, 219,380 (3.3%) underwent surgery. Non-White race (OR 0.80-0.91, p < 0.001) and nonprivate insurance (OR 0.76-0.83, p < 0.001) were associated with lower odds of receiving surgery. Among surgical admissions, presenting severity, including of myelopathy and plegia, was elevated among non-White, nonprivate insurance, and low-income admissions (all p < 0.001). Black race (OR 0.70, p < 0.001), Medicare (OR 0.70, p < 0.001), Medicaid (OR 0.90, p < 0.001), and lower income (OR 0.88-0.93, all p < 0.001) were associated with decreased odds of favorable discharge disposition. Increased LOS and costs were observed among non-White (+6%-10% in LOS and +5%-9% in costs, both p < 0.001) and Medicaid (+16% in LOS and +6% in costs, both p < 0.001) admissions. SNH treatment was also associated with higher mortality (OR 1.49, p < 0.001) and complication (OR 1.20, p < 0.001) rates. From 2002 to 2019, disposition improved annually for Medicaid patients (OR 1.03 per year, p = 0.022) but worsened for Black patients (OR 0.98 per year, p = 0.046). Random forest models identified household income as the most important predictor of discharge disposition. CONCLUSIONS: For spine tumor admissions, SDoH predicted surgical intervention, presenting severity, and perioperative outcomes. Over 2 decades, disparities improved for Medicaid patients but worsened for Black patients. Finally, SDoH significantly improve prognostic accuracy for outcomes after spine tumor surgery. Further study toward ameliorating patient disparities for this population is warranted.

3.
J Neurosurg ; : 1-10, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968623

RESUMO

OBJECTIVE: Despite the proven efficacy of surgical intervention for achieving seizure freedom and improved quality of life for many epilepsy patients, this treatment remains underutilized. In this study, the authors assessed sociodemographic trends in epilepsy surgery in the National Inpatient Sample (NIS) and the Kids' Inpatient Database (KID) and sought to determine whether disparities in surgical intervention for epilepsy may be attributed to insurance and comorbidity status. METHODS: This cross-sectional study utilized data from the NIS database and KID from the Healthcare Cost and Utilization Project between the years 2012 and 2018. Outcomes of interest were rates of neurosurgical intervention, including resection, neuromodulation, or laser ablation. The authors utilized logit regression models to test the association between rates of neurosurgical intervention and the variables of interest and calculated the adjusted mean proportion of patients who received surgery using marginal effects. RESULTS: Of 336,015 admissions with intractable epilepsy in the NIS, 6.1% were patients who underwent neurosurgical treatment. Of 39,655 admissions from KID, 5.0% received surgical treatment. Private insurance was associated with a greater odds of surgical intervention compared with Medicaid (NIS: OR 1.63, KID: OR 1.62; p < 0.001). Patients assigned White race had an increased odds ratio of undergoing surgery when compared with those assigned Black race, adjusted for comorbidity burden (NIS: OR 1.59, p < 0.001; KID: OR 1.44, p = 0.027). Patients with an Elixhauser Comorbidity Index score of 0 or 1 were associated with a lower likelihood of surgery when compared to their higher scoring counterparts who had 4 or more comorbidities (NIS: OR 0.74, KID: OR 0.62; both p < 0.001). CONCLUSIONS: This study demonstrates that marginalized patients and those with Medicaid had decreased odds of neurosurgical intervention for epilepsy. Results of this research support the need for increased attention toward epilepsy patients from marginalized groups. Further investigation into the root cause of socioeconomic inequities in epilepsy surgery is necessary.

4.
Neurosurgery ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990004

RESUMO

BACKGROUND AND OBJECTIVES: The "July Effect" hypothesizes increased morbidity and mortality after the addition of inexperienced physicians at the beginning of an academic year. However, the impact of newer members on neurosurgical teams managing patients with traumatic brain injury (TBI) has yet to be examined. This study conducted a nationwide analysis to evaluate the existence of the "July Effect" in the setting of patients with TBI. METHODS: The Healthcare Cost and Utilization Project Central Distributor's National Inpatient Sample data set was queried for patients with TBI using International Classification of Diseases (ICD)-9 and ICD-10 codes. Discharges were included for diagnoses of traumatic epidural, subdural, or subarachnoid hemorrhages. Only patients treated at teaching hospitals were included to ensure resident involvement in care. Patients were grouped into July admission and non-July admission cohorts. A subgroup of patients with neurotrauma undergoing any form of cranial surgery was created. Perioperative variables were recorded. Rates of different complications were assayed. Groups were compared using χ2 tests (qualitative variables) and t-tests or Mann-Whitney U-tests (quantitative variables). Logistic regression was used for binary variables. Gamma log-linked regression was used for continuous variables. RESULTS: The National Inpatient Sample database yielded a weighted average of 3 160 452 patients, of which 312 863 (9.9%) underwent surgical management. Patients admitted to the hospital in July had a 5% decreased likelihood of death (P = .027), and a 5.83% decreased likelihood of developing a complication (P < .001) compared with other months of the year. July admittance to a hospital showed no significant impact on mean length of stay (P = .392) or routine discharge (P = .147). Among patients with TBI who received surgical intervention, July admittance did not significantly affect the likelihood of death (P = .053), developing a complication (P = .477), routine discharge (P = .986), or mean length of stay (P = .385). CONCLUSION: The findings suggested that there is no "July Effect" on patients with TBI treated at teaching hospitals in the United States.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38967434

RESUMO

BACKGROUND AND OBJECTIVES: Giant pituitary adenomas (GPAs) are a challenging clinical entity, composing 5% to 15% of all pituitary adenomas. While the endoscopic endonasal transsphenoidal (EET) approach has surpassed the microsurgical transsphenoidal (MT) and transcranial (TC) approaches as the first-line surgical modality in most institutions, a systematic review comparing the 3 approaches has not been undertaken since 2012. Given growing adoption of EET and development of novel operative techniques over the past decade, an updated comparison of GPA surgical modalities is warranted. METHODS: We identified all studies related to the surgical management of GPAs in PubMed, Embase, and Web of Science from inception to December 31, 2021. End points assessed included gross total resection (GTR) rates, postoperative visual improvement, mortality, and perioperative complications. RESULTS: After screening of 1701 studies, we identified 45 studies on the surgical management of GPAs for meta-analysis. Thirty-one used the EET approach (n = 1413), 11 studies used the MT approach (n = 601), and 10 used the TC approach (n = 416). The cumulative number of patients treated by EET did not exceed that of patients treated by the TC or MT approaches until 2014 and 2015, respectively. Despite patients undergoing EET having the highest average tumor diameter, pooled rates for GTR were significantly higher for EET (42%) than MT (33%, P < .001) and TC (8%, P < .001) and EET similarly exhibited superior rates of visual improvement (85%) than MT (73%, P < .001) and TC (56%, P < .001). Mortality rates were comparable between EET (0.6%) and MT (1.6%), but EET had significantly lower mortality than TC (2.7%, P < .001). Compared with MT, EET had lower rates of hypopituitarism (8.5% vs 14.9%, P = .012) but higher rates of diabetes insipidus (3.1% vs 0.5%, P = .001). CONCLUSION: In an updated meta-analysis of 1413 patients with GPA, EET resection conferred significantly higher rates of visual improvement and GTR, when compared with the MT and TC approaches.

6.
Oper Neurosurg (Hagerstown) ; 27(4): 491-499, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38752769

RESUMO

BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.


Assuntos
Cavidades Cranianas , Forâmen Jugular , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Cavidades Cranianas/cirurgia , Adulto , Forâmen Jugular/cirurgia , Idoso , Veias Jugulares/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Resultado do Tratamento , Adulto Jovem
7.
Nat Cancer ; 5(3): 517-531, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38216766

RESUMO

We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII+ glioblastoma (GBM) (n = 7). The primary outcome was safety, and no dose-limiting toxicity was observed. Secondary outcomes included median progression-free survival (5.2 months; 90% confidence interval (CI), 2.9-6.0 months) and median overall survival (11.8 months; 90% CI, 9.2-14.2 months). In exploratory analyses, comparison of the TME in tumors harvested before versus after CAR + aPD1 administration demonstrated substantial evolution of the infiltrating myeloid and T cells, with more exhausted, regulatory, and interferon (IFN)-stimulated T cells at relapse. Our study suggests that the combination of CAR T cells and PD-1 inhibition in GBM is safe and biologically active but, given the lack of efficacy, also indicates a need to consider alternative strategies.


Assuntos
Anticorpos Monoclonais Humanizados , Glioblastoma , Humanos , Glioblastoma/terapia , Receptores ErbB , Recidiva Local de Neoplasia/metabolismo , Linfócitos T , Microambiente Tumoral
8.
JAMA Surg ; 159(1): 87-95, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37966807

RESUMO

Importance: The progression of artificial intelligence (AI) text-to-image generators raises concerns of perpetuating societal biases, including profession-based stereotypes. Objective: To gauge the demographic accuracy of surgeon representation by 3 prominent AI text-to-image models compared to real-world attending surgeons and trainees. Design, Setting, and Participants: The study used a cross-sectional design, assessing the latest release of 3 leading publicly available AI text-to-image generators. Seven independent reviewers categorized AI-produced images. A total of 2400 images were analyzed, generated across 8 surgical specialties within each model. An additional 1200 images were evaluated based on geographic prompts for 3 countries. The study was conducted in May 2023. The 3 AI text-to-image generators were chosen due to their popularity at the time of this study. The measure of demographic characteristics was provided by the Association of American Medical Colleges subspecialty report, which references the American Medical Association master file for physician demographic characteristics across 50 states. Given changing demographic characteristics in trainees compared to attending surgeons, the decision was made to look into both groups separately. Race (non-White, defined as any race other than non-Hispanic White, and White) and gender (female and male) were assessed to evaluate known societal biases. Exposures: Images were generated using a prompt template, "a photo of the face of a [blank]", with the blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries on 3 continents (the US, Nigeria, and China). Main Outcomes and Measures: The study compared representation of female and non-White surgeons in each model with real demographic data using χ2, Fisher exact, and proportion tests. Results: There was a significantly higher mean representation of female (35.8% vs 14.7%; P < .001) and non-White (37.4% vs 22.8%; P < .001) surgeons among trainees than attending surgeons. DALL-E 2 reflected attending surgeons' true demographic data for female surgeons (15.9% vs 14.7%; P = .39) and non-White surgeons (22.6% vs 22.8%; P = .92) but underestimated trainees' representation for both female (15.9% vs 35.8%; P < .001) and non-White (22.6% vs 37.4%; P < .001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively; P < .001) and non-White (0.5% and 0.6%, respectively; P < .001) surgeons than DALL-E 2 or true demographic data. Geographic-based prompting increased non-White surgeon representation but did not alter female representation for all models in prompts specifying Nigeria and China. Conclusion and Relevance: In this study, 2 leading publicly available text-to-image generators amplified societal biases, depicting over 98% surgeons as White and male. While 1 of the models depicted comparable demographic characteristics to real attending surgeons, all 3 models underestimated trainee representation. The study suggests the need for guardrails and robust feedback systems to minimize AI text-to-image generators magnifying stereotypes in professions such as surgery.


Assuntos
Especialidades Cirúrgicas , Cirurgiões , Estados Unidos , Humanos , Masculino , Feminino , Estudos Transversais , Inteligência Artificial , Demografia
9.
Mol Diagn Ther ; 27(6): 643-660, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37700186

RESUMO

Chimeric antigen receptor T-cell therapies have transformed the management of hematologic malignancies but have not yet demonstrated consistent efficacy in solid tumors. Glioblastoma is the most common primary malignant brain tumor in adults and remains a major unmet medical need. Attempts at harnessing the potential of chimeric antigen receptor T-cell therapy for glioblastoma have resulted in glimpses of promise but have been met with substantial challenges. In this focused review, we discuss current and future strategies being developed to optimize chimeric antigen receptor T cells for efficacy in patients with glioblastoma, including the identification and characterization of new target antigens, reversal of T-cell dysfunction with novel chimeric antigen receptor constructs, regulatable platforms, and gene knockout strategies, and the use of combination therapies to overcome the immune-hostile microenvironment.


Assuntos
Glioblastoma , Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Glioblastoma/genética , Glioblastoma/terapia , Linfócitos T , Imunoterapia Adotiva/métodos , Microambiente Tumoral
10.
Neurosurgery ; 93(6): 1353-1365, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581444

RESUMO

BACKGROUND AND OBJECTIVES: Interest surrounding generative large language models (LLMs) has rapidly grown. Although ChatGPT (GPT-3.5), a general LLM, has shown near-passing performance on medical student board examinations, the performance of ChatGPT or its successor GPT-4 on specialized examinations and the factors affecting accuracy remain unclear. This study aims to assess the performance of ChatGPT and GPT-4 on a 500-question mock neurosurgical written board examination. METHODS: The Self-Assessment Neurosurgery Examinations (SANS) American Board of Neurological Surgery Self-Assessment Examination 1 was used to evaluate ChatGPT and GPT-4. Questions were in single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests were used to assess performance differences in relation to question characteristics. RESULTS: ChatGPT (GPT-3.5) and GPT-4 achieved scores of 73.4% (95% CI: 69.3%-77.2%) and 83.4% (95% CI: 79.8%-86.5%), respectively, relative to the user average of 72.8% (95% CI: 68.6%-76.6%). Both LLMs exceeded last year's passing threshold of 69%. Although scores between ChatGPT and question bank users were equivalent ( P = .963), GPT-4 outperformed both (both P < .001). GPT-4 answered every question answered correctly by ChatGPT and 37.6% (50/133) of remaining incorrect questions correctly. Among 12 question categories, GPT-4 significantly outperformed users in each but performed comparably with ChatGPT in 3 (functional, other general, and spine) and outperformed both users and ChatGPT for tumor questions. Increased word count (odds ratio = 0.89 of answering a question correctly per +10 words) and higher-order problem-solving (odds ratio = 0.40, P = .009) were associated with lower accuracy for ChatGPT, but not for GPT-4 (both P > .005). Multimodal input was not available at the time of this study; hence, on questions with image content, ChatGPT and GPT-4 answered 49.5% and 56.8% of questions correctly based on contextual context clues alone. CONCLUSION: LLMs achieved passing scores on a mock 500-question neurosurgical written board examination, with GPT-4 significantly outperforming ChatGPT.


Assuntos
Neurocirurgia , Humanos , Procedimentos Neurocirúrgicos , Razão de Chances , Autoavaliação (Psicologia) , Coluna Vertebral
12.
J Clin Med ; 13(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38202013

RESUMO

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. The FT specimens from 288 patients who underwent spinal cord detethering from 2013 to 2021 were analyzed. The histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. The patient details were extracted from electronic medical records. The study found that 97.6% of the FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.

14.
J Neurosurg Case Lessons ; 4(4): CASE22213, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-36046265

RESUMO

BACKGROUND: Tumoral calcinosis is an uncommon disease resulting from dystrophic calcium phosphate crystal deposition, with only 7% of cases involving the spine, and it may diagnostically mimic neoplasms. OBSERVATIONS: In this case, a 54-year-old woman with history of systemic scleroderma presented with 10 months of progressive left lumbosacral pain. Imaging revealed an expansile, 4 × 7-cm, well-circumscribed mass in the lumbosacral spine with L5-S1 neuroforaminal compression. Because intractable pain and computed tomography (CT)-guided needle biopsy did not entirely rule out malignancy, operative management was pursued. The patient underwent L4-S2 laminectomies, left L5-S1 facetectomy, L5 and S1 pediculectomies, and en bloc resection, performed under stereotactic CT-guided intraoperative navigation. Subsequently, instrumented fusion was performed with L4 and L5 pedicle screws and S2 alar-iliac screws. Pathological examination was consistent with tumoral calcinosis, with multiple nodules of amorphous basophilic granular calcified material lined by histiocytes. There was no evidence of recurrence or neurological deficits at 5-month follow-up. LESSONS: Because spinal tumoral calcinosis may mimic neoplasms on imaging or gross intraoperative appearance, awareness of this clinical entity is essential for any spine surgeon. A review of all case reports of lumbosacral tumoral calcinosis (n = 14 from 1952 to 2016) was additionally performed. The case featured in this report presents the first known case of navigation-assisted resection of lumbosacral tumoral calcinosis.

15.
Front Immunol ; 13: 872756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603165

RESUMO

The epidermal growth factor receptor variant III (EGFRvIII) has been investigated as a therapeutic target for chimeric antigen receptor (CAR) T cell therapy in glioblastoma. Earlier research demonstrated that phenotypic and genotypic characteristics in T cells and CAR T product predicted therapeutic success in hematologic malignancies, to date no determinants for clinical response in solid tumors have been identified. We analyzed apheresis and infusion products from the first-in-human trial of EGFRvIII-directed CAR T for recurrent glioblastoma (NCT02209376) by flow cytometry. Clinical response was quantified via engraftment in peripheral circulation and progression-free survival (PFS), as determined by the time from CAR T infusion to first radiographic evidence of progression. The CD4+CAR T cell population in patient infusion products demonstrated PD1 expression which positively correlated with AUC engraftment and PFS. On immune checkpoint inhibitor analysis, CTLA-4, TIM3, and LAG3 did not exhibit significant associations with engraftment or PFS. The frequencies of PD1+GZMB+ and PD1+HLA-DR+ CAR T cells in the CD4+ infusion products were directly proportional to AUC and PFS. No significant associations were observed within the apheresis products. In summary, PD1 in CAR T infusion products predicted peripheral engraftment and PFS in recurrent glioblastoma.


Assuntos
Glioblastoma , Receptores de Antígenos Quiméricos , Receptores ErbB , Glioblastoma/patologia , Humanos , Recidiva Local de Neoplasia/metabolismo , Linfócitos T
16.
J Neurooncol ; 158(3): 349-357, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35503190

RESUMO

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Glioblastoma/epidemiologia , Glioblastoma/cirurgia , Humanos , Razão de Chances , Estudos Retrospectivos , Fatores Socioeconômicos
17.
Cancer Immunol Res ; 10(7): 800-810, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507919

RESUMO

Glioblastoma (GBM) is an immunologically "cold" tumor characterized by poor responsiveness to immunotherapy. Standard of care for GBM is surgical resection followed by chemoradiotherapy and maintenance chemotherapy. However, tumor recurrence is the norm, and recurring tumors are found frequently to have acquired molecular changes (e.g., mutations) that may influence their immunobiology. Here, we compared the immune contexture of de novo GBM and recurrent GBM (rGBM) using high-dimensional cytometry and multiplex IHC. Although myeloid and T cells were similarly abundant in de novo and rGBM, their spatial organization within tumors differed and was linked to outcomes. In rGBM, T cells were enriched and activated in perivascular regions and clustered with activated macrophages and fewer regulatory T cells. Moreover, a higher expression of phosphorylated STAT1 by T cells in these regions at recurrence was associated with a favorable prognosis. Together, our data identify differences in the immunobiology of de novo GBM and rGBM and identify perivascular T cells as potential therapeutic targets. See related Spotlight by Bayik et al., p. 787.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Quimiorradioterapia , Glioblastoma/genética , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico
18.
Neurosurgery ; 91(2): 312-321, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35411872

RESUMO

BACKGROUND: Patient frailty is predictive of higher neurosurgical morbidity and mortality. However, existing frailty measures are hindered by lack of specificity to neurosurgery. OBJECTIVE: To analyze the association between 3 risk stratification scores and outcomes for nationwide vestibular schwannoma (VS) resection admissions and develop a custom VS risk stratification score. METHODS: We identified all VS resection admissions in the National Inpatient Sample (2002-2017). Three risk stratification scores were analyzed: modified Frailty Index-5, modified Frailty Index-11(mFI-11), and Charlson Comorbidity Index (CCI). Survey-weighted multivariate regression evaluated associations between frailty and inpatient outcomes, adjusting for patient demographics, hospital characteristics, and disease severity. Subsequently, we used k -fold cross validation and Akaike Information Criterion-based model selection to create a custom risk stratification score. RESULTS: We analyzed 32 465 VS resection admissions. High frailty, as identified by the mFI-11 (odds ratio [OR] = 1.27, P = .021) and CCI (OR = 1.72, P < .001), predicted higher odds of perioperative complications. All 3 scores were also associated with lower routine discharge rates and elevated length of stay (LOS) and costs (all P < .05). Our custom VS-5 score ( https://skullbaseresearch.shinyapps.io/vs-5_calculator/ ) featured 5 variables (age ≥60 years, hydrocephalus, preoperative cranial nerve palsies, diabetes mellitus, and hypertension) and was predictive of higher mortality (OR = 6.40, P = .001), decreased routine hospital discharge (OR = 0.28, P < .001), and elevated complications (OR = 1.59, P < .001), LOS (+48%, P < .001), and costs (+23%, P = .001). The VS-5 outperformed the modified Frailty Index-5, mFI-11, and CCI in predicting routine discharge (all P < .001), including in a pseudoprospective cohort (2018-2019) of 3885 admissions. CONCLUSION: Patient frailty predicted poorer inpatient outcomes after VS surgery. Our custom VS-5 score outperformed earlier risk stratification scores.


Assuntos
Fragilidade , Neuroma Acústico , Denervação , Fragilidade/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
19.
Otolaryngol Clin North Am ; 55(2): 351-379, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35365313

RESUMO

Giant pituitary adenomas (GPAs) comprise 5% to 15% of pituitary adenomas, but have higher rates of extrasellar invasion, subtotal resection, surgical morbidity, and recurrence. With the possible exception of giant prolactinomas, GPAs require surgical decompression. On review of 3 decades of case series encompassing 699 microsurgical transsphenoidal (MT), 1060 endoscopic endonasal trans-sphenoidal (EET), and 513 transcranial (TC) patients, gross total resection and recurrence rates were comparable across modalities, but the EET approach had lower perioperative mortality and superior restoration of visual function. Each approach has unique indications. Combined EET-TC approaches for minimizing residual tumor represent another area of study.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/cirurgia , Endoscopia , Humanos , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
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