CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy.

Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.

Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.

The Tumor Immune Microenvironment in Primary CNS Neoplasms: A Review of Current Knowledge and Therapeutic Approaches.

Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis, and response to therapy across patients and tumor grades. This review covers the tumor microenvironment of various primary CNS neoplasms, with a focus on glioblastoma and meningioma. Additionally, current therapeutic strategies based on elements of the tumor microenvironment, including checkpoint inhibitor therapy and immunotherapeutic vaccines, are discussed.

Internal neurolysis versus intraoperative glycerin rhizotomy for trigeminal neuralgia.

OBJECTIVE: Internal neurolysis (IN) and intraoperative glycerin rhizotomy (ioGR) are emerging surgical options for patients with trigeminal neuralgia without neurovascular contact. The objective of this study was to compare the neurological outcomes of patients who underwent IN with those of patients who underwent ioGR. METHODS: The authors retrospectively reviewed all patients who underwent IN or ioGR for trigeminal neuralgia at our institution. Patient demographic characteristics and immediate postoperative outcomes, as well as long-term neurological outcomes, were compared. RESULTS: Of 1044 patients who underwent open surgical treatment for trigeminal neuralgia, 56 patients underwent IN and 91 underwent ioGR. Of these 147 patients, 37 had no evidence of intraoperative neurovascular conflict. All patients who underwent IN and 96.7% of patients who underwent ioGR had immediate postoperative pain relief. At last follow-up, patients who underwent IN had lower Barrow Neurological Institute (BNI) pain intensity scores (p = 0.05), better BNI facial numbness scores (p < 0.01), and a greater degree of pain improvement (p = 0.05) compared with those who underwent ioGR. Patients who underwent IN also had significantly lower rates of symptomatic pain recurrence (p < 0.01) at last follow-up over an average of 9.5 months. CONCLUSIONS: IN appears to provide patients with a greater degree of pain relief, lower rates of facial numbness, and lower rates of pain recurrence compared with ioGR. Future prospective studies will better characterize long-term pain recurrence and outcomes.

Machine Learning Models for Predicting Postoperative Outcomes following Skull Base Meningioma Surgery.

Objective While predictive analytic techniques have been used to analyze meningioma postoperative outcomes, to our knowledge, there have been no studies that have investigated the utility of machine learning (ML) models in prognosticating outcomes among skull base meningioma patients. The present study aimed to develop models for predicting postoperative outcomes among skull base meningioma patients, specifically prolonged hospital length of stay (LOS), nonroutine discharge disposition, and high hospital charges. We also validated the predictive performance of our models on out-of-sample testing data. Methods Patients who underwent skull base meningioma surgery between 2016 and 2019 at an academic institution were included in our study. Prolonged hospital LOS and high hospital charges were defined as >4 days and >$47,887, respectively. Elastic net logistic regression algorithms were trained to predict postoperative outcomes using 70% of available data, and their predictive performance was evaluated on the remaining 30%. Results A total of 265 patients were included in our final analysis. Our cohort was majority female (77.7%) and Caucasian (63.4%). Elastic net logistic regression algorithms predicting prolonged LOS, nonroutine discharge, and high hospital charges achieved areas under the receiver operating characteristic curve of 0.798, 0.752, and 0.592, respectively. Further, all models were adequately calibrated as determined by the Spiegelhalter Z -test ( p >0.05). Conclusion Our study developed models predicting prolonged hospital LOS, nonroutine discharge disposition, and high hospital charges among skull base meningioma patients. Our models highlight the utility of ML as a tool to aid skull base surgeons in providing high-value health care and optimizing clinical workflows.

A Potential Role for Steroids in Acute Pain Management in Patients with Trigeminal Neuralgia.

OBJECTIVE: Effective therapies for acute pain management in trigeminal neuralgia (TN) are limited. We aimed to investigate the role of steroids in TN patients experiencing acute pain flares. METHODS: We retrospectively reviewed patients presenting to the emergency department of a tertiary care institution between 2014 and 2020 for acute TN pain flares. Patients were divided into those who received steroids versus those who did not. Presenting characteristics, admission and surgical intervention rates, Barrow Neurological Institute pain scores, pain recurrence rates, and surgical intervention within 6 months of discharge were obtained for each patient. RESULTS: Our cohort comprised 151 patients, of whom 40 (26.5%) received steroids before admission and/or discharge. These patients were less likely to undergo surgical intervention to treat acute pain (P = 0.023). Specifically, patients receiving steroids were less likely to undergo combined glycerin and radiofrequency rhizotomy compared with patients not receiving steroids (P = 0.012). Frequency and dosage of opioid administration did not differ between groups. The steroids group demonstrated a lower average Barrow Neurological Institute pain score on discharge compared with the no steroids group (P = 0.013). Patients receiving steroids for acute pain management were less likely to undergo surgical intervention within 6 months of discharge than patients who did not receive steroids (P = 0.033). CONCLUSIONS: Steroid administration in patients with acute TN pain flares may reduce the likelihood of surgical intervention both during admission and within 6 months of discharge. Future prospective studies should examine the efficacy of steroids as an adjunctive medication in acute TN pain management.

Spinal cord untethering and midline myelotomy for delayed, symptomatic post-traumatic syringomyelia due to retained ballistic fragments: case report.

INTRODUCTION: Post-traumatic syringomyelia is an uncommon complication after traumatic spinal cord injury. This case study details our decision-making and surgical approach for a patient with symptomatic post-traumatic syringomyelia after sustaining a gunshot wound. CASE PRESENTATION: A 24-year-old man with past medical history of distant American Spinal Injury Association Impairment Grade B spinal cord injury due to ballistic injury developed delayed post-traumatic syringomyelia, resulting in unilateral sensory loss and left upper extremity weakness. CT and MR imaging revealed a syrinx spanning his cervical and thoracic spine causing significant spinal cord compression. To relieve achieve decompression and restore CSF flow dynamics, we performed a bony extradural decompression, bullet fragment extraction, spinal cord untethering, and midline myelotomy. Postoperatively, the patient demonstrated clinical and radiographical improvement. DISCUSSION: Post-traumatic syringomyelia is potentially morbid sequalae of spinal cord injuries. Suspicion for post-traumatic syringomyelia should be maintained in patients with delayed, progressive neurologic deficits. In this setting, surgical intervention may require extradural and intradural procedures to mitigate neural compression along the dilated central canal by the syrinx.

Reexamining the Role of Postoperative ICU Admission for Patients Undergoing Elective Craniotomy: A Systematic Review.

OBJECTIVES: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy. DATA SOURCES: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021. STUDY SELECTION: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care. DATA EXTRACTION: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively. DATA SYNTHESIS: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation. CONCLUSIONS: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.

Synthesizing Molecular and Immune Characteristics to Move Beyond WHO Grade in Meningiomas: A Focused Review.

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

Clinical predictors of survival for patients with atypical teratoid/rhabdoid tumors.

PURPOSE: Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant central nervous system (CNS) neoplasms of the young. Our study analyzed a large AT/RT cohort from the National Cancer Database (NCDB) to elucidate predictors of short-term mortality and overall survival (OS). METHODS: Information was collected on patients with histologically confirmed AT/RT using the NCDB (2004-2016). Kaplan-Meier analysis indicated OS. Prognostic factors for 30-day mortality, 90-day mortality, and OS were determined via multivariate Cox proportional hazards (CPH) and logistic regression models. RESULTS: Our cohort of 189 patients had a median age of 1 year (IQR [1, 4]) and tumor size of 4.7 ± 2.0 cm at diagnosis. Seventy-two percent were under 3 years old; 55.6% were male and 71.0% were Caucasian. Fifty (27.2%) patients received only surgery (S) (OS = 5.91 months), 51 (27.7%) received surgery and chemotherapy (S + CT) (OS = 11.2 months), and 9 (4.89%) received surgery and radiotherapy (S + RT) (OS = 10.3 months). Forty-five (24.5%) received S + CT + RT combination therapy (OS = 45.4 months), 13 (17.1%) received S + CT + BMT/SCT (bone marrow or stem cell transplant) (OS = 55.5 months), and 16 (8.70%) received S + CT + RT + BMT/SCT (OS = 68.4 months). Bivariate analysis of dichotomized age (HR = 0.550, 95% CI [0.357, 0.847], p = 0.0067) demonstrated significantly increased patient survival if diagnosed at or above 1 year old. On multivariate analysis, administration of S + CT + RT, S + CT + BMT/SCT, or S + CT + RT + BMT/SCT combination therapy predicted significantly (p < 0.05) increased OS compared to surgery alone. CONCLUSION: AT/RTs are CNS tumors where those diagnosed under 1 year old have a significantly worse prognosis. Our study demonstrates that while traditional CT, RT, and BMT/SCT combination regimens prolong life, overall survival in this population is still low.

Case Series in the Utility of Invasive Blood Pressure Monitoring in Microvascular Decompression.

BACKGROUND: The utility of arterial lines in microvascular decompression (MVD) is not well described. OBJECTIVE: To examine the safety and costs of arterial lines compared with noninvasive blood pressure (NIBP) monitoring in MVDs. METHODS: We retrospectively reviewed patients undergoing MVD from 2012 to 2020. Patients were grouped by procedure date from 2012 to 2014 and 2015 to 2020, reflecting our institution's decreasing trend in arterial line placement around 2014 to 2015. Patient features, intraoperative characteristics, and postoperative complications were collected for all cases. Statistical differences were evaluated using chi-squared analyses and t-tests. RESULTS: Eight hundred fifty-eight patients underwent MVDs, with 204 between 2012 and 2014 and 654 between 2015 and 2020. Over time, the frequency of arterial line placement decreased from 64.2% to 30.1%, P < .001. Arterial lines involved 11 additional minutes of preincision time, P < .001. Patients with arterial lines required both increased doses and costs of vasoactive medications intraoperatively. Patients receiving arterial lines demonstrated no significant differences in complications compared with patients with NIBP monitoring. On average, patients with arterial lines incurred $802 increased costs per case compared with NIBP monitoring. CONCLUSION: NIBP monitoring in MVDs provides neurologically and hemodynamically safe outcomes compared with invasive blood pressure monitoring. For patients without significant cardiopulmonary risk factors, NIBP monitoring may be a cost-effective alternative in MVDs.

Endotypes and the Path to Precision in Moderate and Severe Traumatic Brain Injury.

Heterogeneity is recognized as a major barrier in efforts to improve the care and outcomes of patients with traumatic brain injury (TBI). Even within the narrower stratum of moderate and severe TBI, current management approaches do not capture the complexity of this condition characterized by manifold clinical, anatomical, and pathophysiologic features. One approach to heterogeneity may be to resolve undifferentiated TBI populations into endotypes, subclasses that are distinguished by shared biological characteristics. The endotype paradigm has been explored in a range of medical domains, including psychiatry, oncology, immunology, and pulmonology. In intensive care, endotypes are being investigated for syndromes such as sepsis and acute respiratory distress syndrome. This review provides an overview of the endotype paradigm as well as some of its methods and use cases. A conceptual framework is proposed for endotype research in moderate and severe TBI, together with a scientific road map for endotype discovery and validation in this population.

A Brief History of Machine Learning in Neurosurgery.

The history of machine learning in neurosurgery spans three decades and continues to develop at a rapid pace. The earliest applications of machine learning within neurosurgery were first published in the 1990s as researchers began developing artificial neural networks to analyze structured datasets and supervised tasks. By the turn of the millennium, machine learning had evolved beyond proof-of-concept; algorithms had success detecting tumors in unstructured clinical imaging, and unsupervised learning showed promise for tumor segmentation. Throughout the 2000s, the role of machine learning in neurosurgery was further refined. Well-trained models began to consistently best expert clinicians at brain tumor diagnosis. Additionally, the digitization of the healthcare industry provided ample data for analysis, both structured and unstructured. By the 2010s, the use of machine learning within neurosurgery had exploded. The rapid deployment of an exciting new toolset also led to the growing realization that it may offer marginal benefit at best over conventional logistical regression models for analyzing tabular datasets. Additionally, the widespread adoption of machine learning in neurosurgical clinical practice continues to lag until additional validation can ensure generalizability. Many exciting contemporary applications nonetheless continue to demonstrate the unprecedented potential of machine learning to revolutionize neurosurgery when applied to appropriate clinical challenges.

Synergy between glutamate modulation and anti-programmed cell death protein 1 immunotherapy for glioblastoma.

OBJECTIVE: Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strategies. It is well understood that GBM increases glutamate in the tumor microenvironment (TME); however, the significance of this is not well understood. The authors posit that glutamate upregulation in the GBM TME is immunosuppressive. The authors utilized a novel glutamate modulator, BHV-4157, to determine synergy between glutamate modulation and the well-established anti-PD-1 immunotherapy for GBM. METHODS: C57BL/6J mice were intracranially implanted with luciferase-tagged GL261 glioma cells. Mice were randomly assigned to the control, anti-PD-1, BHV-4157, or combination anti-PD-1 plus BHV-4157 treatment arms, and median overall survival was assessed. In vivo microdialysis was performed at the tumor site with administration of BHV-4157. Intratumoral immune cell populations were characterized with immunofluorescence and flow cytometry. RESULTS: The BHV-4157 treatment arm demonstrated improved survival compared with the control arm (p < 0.0001). Microdialysis demonstrated that glutamate concentration in TME significantly decreased after BHV-4157 administration. Immunofluorescence and flow cytometry demonstrated increased CD4+ T cells and decreased Foxp3+ T cells in mice that received BHV-4157 treatment. No survival benefit was observed when CD4+ or CD8+ T cells were depleted in mice prior to BHV-4157 administration (p < 0.05). CONCLUSIONS: In this study, the authors showed synergy between anti-PD-1 immunotherapy and glutamate modulation. The authors provide a possible mechanism for this synergistic benefit by showing that BHV-4157 relies on CD4+ and CD8+ T cells. This study sheds light on the role of excess glutamate in GBM and provides a basis for further exploring combinatorial approaches for the treatment of this disease.

Mutation status and postresection survival of patients with non-small cell lung cancer brain metastasis: implications of biomarker-driven therapy.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS: The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS: Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS: Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

Predicting High-Value Care Outcomes After Surgery for Non-Skull Base Meningiomas.

OBJECTIVE: A need exists to better understand the prognostic factors that influence high-value care outcomes after meningioma surgery. The goal of the present study was to develop predictive models to determine the patients at risk of experiencing an extended hospital length of stay (LOS), nonroutine discharge disposition, and/or a 90-day hospital readmission after non-skull base meningioma resection. METHODS: In the present study, we analyzed the data from 396 patients who had undergone surgical resection of non-skull base meningiomas at a single institution between January 1, 2005 and December 31, 2020. The Mann-Whitney U test was used for bivariate analysis of the continuous variables and the Fisher exact test for bivariate analysis of the categorical variables. A multivariate analysis was conducted using logistic regression models. RESULTS: Most patients had had a falcine or parasagittal meningioma (66.2%), with the remainder having convexity (31.8%) or intraventricular (2.0%) tumors. Nonelective surgery (P < 0.0001) and an increased tumor volume (P = 0.0022) were significantly associated with a LOS >4 days on multivariate analysis. The independent predictors of a nonroutine discharge disposition included male sex (P = 0.0090), nonmarried status (P = 0.024), nonelective surgery (P = 0.0067), tumor location within the parasagittal or intraventricular region (P = 0.0084), and an increased modified frailty index score (P = 0.039). Hospital readmission within 90 days was independently associated with nonprivate insurance (P = 0.010) and nonmarried status (P = 0.0081). Three models predicting for a prolonged LOS, nonroutine discharge disposition, and 90-day readmission were implemented in the form of an open-access, online calculator (available at: https://neurooncsurgery3.shinyapps.io/non_skull_base_meningiomas/). CONCLUSIONS: After external validation, our open-access, online calculator could be useful for assessing the likelihood of adverse postoperative outcomes for patients undergoing surgery of non-skull base meningioma.

Patient-Specific Factors Drive Intensive Care Unit and Total Hospital Length of Stay in Operative Patients with Brain Tumor.

BACKGROUND: Hospital length of stay (LOS) is an important cost driver in neurosurgery. Broader surgical literature has shown that patient-related factors, including comorbidities, and procedure-related factors, such surgeon experience, may be associated with LOS. Because value optimization strategies may be targeted toward either domain, this study investigated the contributions of patient-related and procedure-related factors in predicting prolonged intensive care unit LOS (iLOS) and total hospital LOS (tLOS). METHODS: Data for adult patients undergoing brain tumor surgery (2017-2019) were collected. Bivariate analyses for iLOS and tLOS were performed using the Mann-Whitney U test and Fisher exact test. Variables associated with either outcome with P < 0.10 were included in patient-only, procedure-only, and patient+procedure factor multivariate linear regression models. Model discrimination was quantified using C-statistics. RESULTS: Our 654 patients had a mean age of 57.54 years (standard deviation, ± 14.34 years). For iLOS, the patient-only model significantly outperformed the procedure-only model (P < 0.0001) and performed similarly to the patient+procedure model (P = 0.50). Other than tumor diagnosis, 5-Factor Modified Frailty Index score was the only factor associated with iLOS (P < 0.001) and tLOS (P < 0.001) on multivariate analysis. When predicting prolonged tLOS, the patient-only model significantly outperformed the procedure-only model (P < 0.0001), and performed similarly to patient+procedure models (P = 0.49). CONCLUSIONS: Patient-specific factors are the main drivers of prolonged iLOS and tLOS among patients with brain tumor. Frailty was significantly associated with both iLOS and tLOS on multivariate analysis. Efforts to improve care value should focus on strategies to optimize patient status, such as prehabilitation and enhanced recovery after surgery.

Effect of radiation therapy on overall survival following subtotal resection of adult pilocytic astrocytoma.

OBJECTIVE: Pilocytic astrocytoma (PCA) is a low-grade glioma that primarily presents in children, but can also present in adulthood. Ideal primary treatment for PCA is gross total resection. However, for patients who are only able to undergo subtotal resection, the optimal course of post-operative therapy remains unclear. We investigated the association of patient characteristics and radiation therapy (RT) with overall survival specifically for adult PCA patients who underwent subtotal tumor resection. METHODS: Information on adult patients (age ≥18 years old) who underwent subtotal PCA resection between 2004 and 2016 was collected from the National Cancer Database (NCDB). A multivariate Cox proportional hazards model was utilized to determine factors associated with overall survival. RESULTS: A total of 451 patients were identified. The mean age of our patient cohort was 36.8 years old, and the majority of patients (83.4%) did not receive RT following subtotal PCA resection. Overall median survival was >93.8 months. On multivariate analysis, patients who were older at diagnosis (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.02-1.06, p < 0.01), black (HR = 2.35, CI = 1.05-5.23, p = 0.037), had a Charlson/Deyo comorbidity score ≥ 1 (HR = 2.27, CI = 1.00-5.14, p = 0.049), or received RT during their initial treatment (HR = 3.77, CI = 1.77-8.03, p < 0.01) had a significantly higher risk of death following subtotal PCA resection. CONCLUSION: Post-operative RT was associated with a significantly higher risk of death among adults who underwent subtotal PCA resection. Our findings provide support for further inquiry into the efficacy of RT within this patient population.