Intra-axial Tumors Research Articles

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

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. 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. 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. 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.

Six Years of Neuro-Navigation Assisted Brain Tumor Surgery North Central Nigeria: Progress and Challenges

Introduction: Cranial operations in general have been historically driven by sound anatomical navigation with tremendous success. However, due to the unending desire for perfection, computerized neuro-navigation-assisted cranial surgery has found global usefulness, especially in neuro-oncological services. Our initial experience and challenges with this technology was already published three years ago but it becomes expedient for an update. Aims and Objectives: To report a six-year experience with computerized neuro-navigation assistance in our neuro-oncology surgeries and services. Methodology: Retrospective review of all consecutive cases involving computer-assisted neuro-navigation diagnostic and resective brain tumor operation over a six-year period (January 2016-December 2021). Main study parameters: Clinical diagnostic procedures, operations, histological diagnosis, adjuvant treatments. Data were analyzed using simple descriptive statistics, and results were presented accordingly. Results: Total number of cases 111, Males 70 and Females 41 (M: F = 1.7:1). Age ranges from 8 months to 80 years. The commonest presentation was headache, nausea, and vomiting. Pre-op diagnosis: Intra axial tumors 70/111 (63%), Extra axial tumors 41/111 (36%). Operations: Resection/Debulking of tumor 86/111 (77,4%), with complete EOR of 65/86 (75%). Diagnostic Biopsy 68/111 (61%) with target precision of 100%. Common Histology were Gliomas 50/111 (45%), Meningiomas 41/111 (36.9%), and Metastatic 15/111 (13.5%). Adjuvant treatments and follow-ups were advised accordingly. Conclusions: With computerized neuro-navigation assistance, a wider spectrum of brain tumors were more confidently operated, and adjuvant treatments were easily deployed in line with a precise histological diagnosis for improved neuro-oncology services. But this success was at a huge cost of adopting measures to overcome some inevitable challenges.

Six Years of Neuro-Navigation Assisted Brain Tumor Surgery North Central Nigeria: Progress and Challenges

Introduction: Cranial operations in general have been historically driven by sound anatomical navigation with tremendous success. However, due to the unending desire for perfection, computerized neuro-navigation-assisted cranial surgery has found global usefulness, especially in neuro-oncological services. Our initial experience and challenges with this technology was already published three years ago but it becomes expedient for an update. Aims and Objectives: To report a six-year experience with computerized neuro-navigation assistance in our neuro-oncology surgeries and services. Methodology: Retrospective review of all consecutive cases involving computer-assisted neuro-navigation diagnostic and resective brain tumor operation over a six-year period (January 2016-December 2021). Main study parameters: Clinical diagnostic procedures, operations, histological diagnosis, adjuvant treatments. Data were analyzed using simple descriptive statistics, and results were presented accordingly. Results: Total number of cases 111, Males 70 and Females 41 (M: F = 1.7:1). Age ranges from 8 months to 80 years. The commonest presentation was headache, nausea, and vomiting. Pre-op diagnosis: Intra axial tumors 70/111 (63%), Extra axial tumors 41/111 (36%). Operations: Resection/Debulking of tumor 86/111 (77,4%), with complete EOR of 65/86 (75%). Diagnostic Biopsy 68/111 (61%) with target precision of 100%. Common Histology were Gliomas 50/111 (45%), Meningiomas 41/111 (36.9%), and Metastatic 15/111 (13.5%). Adjuvant treatments and follow-ups were advised accordingly. Conclusions: With computerized neuro-navigation assistance, a wider spectrum of brain tumors were more confidently operated, and adjuvant treatments were easily deployed in line with a precise histological diagnosis for improved neuro-oncology services. But this success was at a huge cost of adopting measures to overcome some inevitable challenges.

Baseline neurocognitive dysfunction is ubiquitous in intrinsic brain tumors– results from a large Indian cohort of patients and analysis of factors associated with domain-specific dysfunction

BackgroundNeurocognitive function (NCF) before surgery is an important marker of baseline performance in patients with brain tumors. Increasingly, neurocognitive deficits (NCD) have been demonstrated in a high proportion of patients. Selection bias (patient, tumor, and surgical procedure related) may influence the prevalence and type of domains involved in patients with gliomas. MethodsWe evaluated baseline NCF in a consecutive cohort of intra-axial tumors in Indian patients (n = 142). A comprehensive battery evaluating five domains – attention & executive function (EF), memory, language, visuospatial function and visuomotor abilities was used. Deficits were categorized as severe and mild-moderate. Factors associated with severe NCD were evaluated. ResultsSevere NCD was present in 90% of the patients, 70% of them having affection of at least 2 domains. Attention-EF, memory and visuomotor speed were most affected. 132 underwent surgery (69 awake, 63 under general anesthesia - GA). The awake cohort had younger patients with lower grade gliomas and more left sided tumors. Multi-domain dysfunction was seen almost equally in awake/GA groups as well as left/right sided tumors. On multivariate analysis, older age, lower educational status and larger tumor volume adversely affected NCF in many of the domains. Only language dysfunction was location specific (temporal lobe tumors) though not laterality (left/right) specific. ConclusionsNCD were seen in a large majority of cases before surgery, including those undergoing awake surgery. Language may be affected even in tumors in the non-dominant hemisphere. Attention-EF and memory are most affected and need to be factored in while assessing patient performance intraoperatively during awake surgery as well as tailoring rehabilitative measures subsequently.

Clinical and histopathological spectrum of cranial small round cell tumors: An experience from a tertiary care center.

Small round cell tumors (SRCTs) are a group of malignant neoplasms with minimal or no differentiation, characterized by the presence of round cells with high nuclear-cytoplasmic ratio. Although SRCTs can occur in any part of the body, involvement of central nervous system (CNS) is uncommon. We aimed to study the clinicopathological spectrum of cranial SRCT diagnosed in our institute over a period of four years (2016-2019). A retrospective review of medical records (2016-2019) with a morphological diagnosis of cranial SRCT was made. Both intra-axial and extra-axial tumors were included. A total of 60 cases were retrieved, and the clinical and histopathological features were studied. Special cytochemical staining and immunohistochemistry were performed, where needed. The mean age at presentation was 18.4 years (range, 1-60 years), with a male-to-female ratio of 2.5:1. The most common site was posterior fossa of brain (n = 28, 47%), followed by dorso-lumbar spine (n = 9, 15%). The most common type of tumor was medulloblastoma (n = 29, 48.3%), followed by Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) (n = 11, 18.3%), non-Hodgkin lymphoma (NHL) (n = 9, 15%), neuroblastoma (n = 3, 5%), and CNS embryonal tumor, NOS (n = 2, 3.3%). One case each of atypical teratoid rhabdoid tumor (ATRT), rhabdomyosarcoma, pineoblastoma, melanoma, rhabdomyosarcoma, and undifferentiated pleomorphic sarcoma was also documented. SRCTs have a variable age of presentation. Their incidence in CNS is low as compared to other organ systems. On light microscopy, the histopathology of these lesions is overlapping, posing a great diagnostic dilemma for the pathologist. The use of ancillary techniques like immunohistochemistry helps in arriving at the correct diagnosis. Treatment strategy and tumor prognosis also vary along the entire spectrum of SRCT, thus making exact characterization essential for proper management.

The current state of the art of primary motor mapping for tumor resection: A focused survey

IntroductionCortical and subcortical motor mapping has advanced the notion of maximal safe resection of intra-axial brain tumours, thereby preserving neurological functions as well as improving survival. Despite being an age-old and established neurosurgical procedure across the world, the strategy and techniques involved in motor mapping have a gamut of variation due to a lack of defined standard protocols. MethodsWe disseminated a structured survey among focused group of neurosurgeons with established practices involving brain mapping. It consisted of 40 questions, split into five sections assessing the practice description, general approach for motor mapping, preference for asleep versus awake mapping, operative techniques and approach to representative tumor cases. Practice-patterns during primary motor mapping for brain tumours were analysed from responses of 51 neurosurgeons. Results60.8 % felt that any lesion even near (without infiltration) was suffice to define “involvement” of the cortical/subcortical motor pathways. 82.4 % felt that motor mapping was necessary for brain tumours involving motor pathways, irrespective of the tumor histology or patient age. 90.2 % opined that tumor location was the predominant factor affecting their choice between awake or asleep mapping. 31.4 % believed that all cases should be performed awake unless patient-related medical, psychological, or anaesthetic contraindications exist, whereas 45.1 % felt that all cases should be performed asleep unless language mapping is required. MRI, DTI-based tractography and intra-operative fluorescence were the most commonly employed surgical adjuncts. ConclusionsThe data from this survey may serve as a preliminary foundation for a more standardized approach to patient selection and the approach to motor mapping for brain tumors.

Staged Open Cranial Surgery for Primary Intra-axial Neoplasms: A Systematic Review

Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications. Conversely, staged surgery for primary intraparenchymal neoplasms is less commonly performed and has not been reported as extensively within the literature. As such, we performed a systematic review to examine the unique surgical indications for staging, timing between stages, specific surgical approaches utilized, and postoperative complications of staged surgery for primary intra-axial neoplasms. A literature search was conducted in August 2021 using PubMed, Web of Science, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of strict inclusion criteria during full text screen. Each included article was then qualitatively assessed and relevant variables-including operative approaches, timing, and outcomes-were extracted for synthesis. Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric and 4 adult patients. Staged approaches were more commonly utilized in the pediatric patient population for resection of astrocytoma and glioma. Pediatric patients had a timing of surgeries ranging from 5-10 days between operations, compared with 18 days to 4 months in adult patients. Complications in pediatric patients were most commonly hemiparesis, hydrocephalus, cranial nerve VI and VII palsies, truncal ataxia, and cerebellar mutism, while complications in adult patients included language and abstract thinking deficits, respiratory failure, and motor weakness. This study reports the first comprehensive review of staged surgical procedures for primary, intra-axial cranial neoplasms. There exists a large degree of heterogeneity in complications resulting from staged surgeries for intra-axial neoplasms, which are similar to complications associated with single-stage surgery for intraparenchymal lesions as well as multi-stage surgeries for skull base lesions.

Pinless Electromagnetic Neuronavigation During Awake Craniotomies: Technical Pearls, Pitfalls, and Nuances

Awake craniotomies are often performed with rigid pin fixation to support optical neuronavigation. Newer electromagnetic (EM) neuronavigation technology now enables unpinned cranial neurosurgery while maintaining robust intraoperative image guidance. Here, we share technical nuances, operative pearls, and lessons learned from our institutional experience using Curve EM neuronavigation during awake, unpinned craniotomies. We describe our process for patient positioning, instrumentation setup, system registration, intraoperative navigation, and surgical adjunct use (e.g., intraoperative neuromonitoring and intraoperative magnetic resonance imaging) in detail. At each step, we provide pearls for success and tips for pitfall avoidance based on our experience. Ten patients underwent awake pinless intra-axial tumor resection using Curve EM neuronavigation from May 2021 to August 2022 with a single surgeon. Postoperative transient neurological deficits were seen in 8 of 10 cases (80.0%), as all resections were taken to functional margins. Of the 9 patients with a 3-month follow-up visit at the time of publication, all 9 (100%) had improved or stable preoperative symptoms. No surgical complications, clinically appreciable inaccuracies, intraoperative losses of registration, unexpected postoperative magnetic resonance imaging findings, or errors related to the use of EM neuronavigation occurred. The technical pearls outlined here willhelp interested neurosurgeons integrate EM neuronavigation into awake craniotomies. In our experience, using unpinned neuronavigation during awake cases provides many advantages to the patient, surgeon, and entire operative team. It has thus become the standard practice at our institution.

Cerebellar Mutism Syndrome After Posterior Fossa Tumor Surgery in Children—A Retrospective Single-Center Study

Cerebellar mutism syndrome (CMS) is a well-known complication following posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus. All pediatric patients who received an intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included for retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery associated, complications and follow-up data were collected and statistically evaluated for association with CMS. 63 surgeries in 60 patients were included with a median age of 8 years. Pilocytic astrocytoma was mostly represented by 50%, followed by medulloblastoma in 28%, and ependymomas in 10%. Complete resection was achieved in 67% versus subtotal in 23%, and partial resection in 10%. Telovelar approach was the most used in 43 % compared to transvermian in 8%. 10 children (17%) developed CMS and showed marked improvement but with residual deficits. Significant risk factors were transvermian approach (p=0.03), vermian splitting whenever added to other approach (p=0.002), initial presentation with acute hydrocephalus (p=0.02), and remaining hydrocephalus after tumor surgery (p=0.004). Our CMS rate compares to those described in literature. Despite the limitations of our study as a retrospective one, we found CMS was not only associated with a transvermian approach, but also occurs after using a telovelar approach, however to a lesser extent. Acute hydrocephalus at initial presentation necessitating urgent management was significantly associated with higher incidence of CMS.

Risk for hydrocephalus, hygroma, and tumor dissemination after ventricular opening during resection of supratentorial neoplasms in children.

The possibility that ventricular opening generates postoperative complications after surgical tumor treatment often restricts the degree of tumor resection. This study aims to determine whether the ventricular opening is associated with more complications in surgeries for resectioning supratentorial intra-axial brain tumors in the pediatric population. A retrospective review analysis was performed of patients treated at IOP/GRAACC between 2002 and 2020 under 19years of age and underwent surgery for supratentorial intra-axial primary brain tumor resection. Data were collected from 43 patients. Glial tumor was more common than non-glial (65% vs. 35%, p = 0.09). The ventricular opening was not related to neoplastic spreads to the neuroaxis (6% vs. 0, p > 0.9) or leptomeningeal (3% vs. 0, p > 0.9). Of the patients whose ventricle was opened, 10% developed hydrocephalus requiring treatment, while none of the patients in the group without ventricular opening developed hydrocephalus (p = 0.5). There was also no statistical difference regarding ventriculitis. Postoperative subdural hygroma formation correlated with the ventricular opening (43% vs. 0, p = 0.003). The survival at 1, 5, and 10years of cases with the ventricular opening was 93.2%, 89.7%, and 75.7%, respectively, while in cases without ventricular opening, it was 100%, 83%, and 83%, respectively, respectively, with no statistical difference between the mortality curves. Our study demonstrated that ventricular violation was not associated with the occurrence of significant complications. It was related to the formation of subdural hygroma, which did not require additional treatment.

Investigation of neurophysiologic and functional connectivity changes following glioma resection using magnetoencephalography.

In patients with glioma, clinical manifestations of neural network disruption include behavioral changes, cognitive decline, and seizures. However, the extent of network recovery following surgery remains unclear. The aim of this study was to characterize the neurophysiologic and functional connectivity changes following glioma surgery using magnetoencephalography (MEG). Ten patients with newly diagnosed intra-axial brain tumors undergoing surgical resection were enrolled in the study and completed at least two MEG recordings (pre-operative and immediate post-operative). An additional post-operative recording 6-8 weeks following surgery was obtained for six patients. Resting-state MEG recordings from 28 healthy controls were used for network-based comparisons. MEG data processing involved artifact suppression, high-pass filtering, and source localization. Functional connectivity between parcellated brain regions was estimated using coherence values from 116 virtual channels. Statistical analysis involved standard parametric tests. Distinct alterations in spectral power following tumor resection were observed, with at least three frequency bands affected across all study subjects. Tumor location-related changes were observed in specific frequency bands unique to each patient. Recovery of regional functional connectivity occurred following glioma resection, as determined by local coherence normalization. Changes in inter-regional functional connectivity were mapped across the brain, with comparable changes in low to mid gamma-associated functional connectivity noted in four patients. Our findings provide a framework for future studies to examine other network changes in glioma patients. We demonstrate an intrinsic capacity for neural network regeneration in the post-operative setting. Further work should be aimed at correlating neurophysiologic changes with individual patients' clinical outcomes.

Diffusion tensor imaging derived metrics in high grade glioma and brain metastasis differentiation

Background: Pretreatment differentiation between glioblastoma and metastasis is a frequently encountered dilemma in neurosurgical practice. Distinction is required for precise planning of resection or radiotherapy, and also for defining further diagnostic procedures. Morphology and spectroscopy imaging features are not specific and frequently overlap. This limitation of magnetic resonance imaging and magnetic resonance spectroscopy was the reason to initiate this study. The aim of the present study was to determine whether the dataset of diffusion tensor imaging metrics contains information which may be used for the distinction between primary and secondary intra-axial neoplasms. Methods: Two diffusion tensor imaging parameters were measured in 81 patients with an expansive, ring-enhancing, intra-axial lesion on standard magnetic resonance imaging (1.5 T system). All tumors were histologically verified glioblastoma or secondary deposit. For qualitative analysis, two regions of interest were defined: intratumoral and immediate peritumoral region (locations 1 and 2, respectively). Fractional anisotropy and mean difusivity values of both groups were compared. Additional test was performed to determine if there was a significant difference in mean values between two locations. Results: A statistically significant difference was found in fractional anisotropy values among two locations, with decreasing values in the direction of neoplastic infiltration, although such difference was not observed in fractional anisotropy values in the group with secondary tumors. Mean difusivity values did not appear helpful in differentiation between these two entities. In both groups there was no significant difference in mean difusivity values, neither in intratumoral nor in peritumoral location. Conclusion: The results of our study justify associating the diffusion tensor imaging technique to conventional morphologic magnetic resonance imaging as an additional diagnostic tool for the distinction between primary and secondary intra-axial lesions. Quantitative analysis of diffusion tensor imaging metric, in particular measurement of fractional anisotropy in peritumoral edema facilitates accurate diagnosis.

The role of sodium fluorescein in pediatric supratentorial intra-axial tumor resection: new insights from a monocentric series of 33 consecutive patients.

The role of sodium fluorescein in pediatric supratentorial intra-axial tumor resection: new insights from a monocentric series of 33 consecutive patients.

The role of sodium fluorescein in pediatric supratentorial intra-axial tumor resection: new insights from a monocentric series of 33 consecutive patients.

Surgical resection represents the mainstay of treatment, in pediatric central nervous system (CNS) tumors, and aggressive resection correlates with prognosis for several histotypes. Sodium fluorescein (SF), a green, water-soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier disruption, acting as a valid tool to improve the extent of resection in tumors enhancing at preoperative MRI. Brain neoplasms represent a heterogeneous group of tumors in the pediatric age, constituting the most common solid cancers; they typically show a varying degree of contrast enhancement on MRI. In March 2016, the authors started a prospective, observational trial to evaluate intraoperative fluorescence's characteristics of CNS tumors, the percentage of extent of resection, thanks to fluorescein aid, and side effects related to fluorescein administration. This report is based on a retrospective analysis of a group of 33 consecutive pediatric patients harboring a supratentorial lesion. In 17 of 33 (51.5%) procedures, fluorescence was reported as intense; in 14 of 33 (42.4%), moderate; and in 2 of 33 (6.1%), slight. Intraoperative fluorescence corresponds to preoperative-MRI-documented contrast enhancement. In 28 of 33 (84.8%) surgical procedures, SF was considered useful; in 2 of 33 (6.1%), partial useful; and in 3 of 33 (9.1%), not essential because the tumor was already recognizable. No adverse effect to SF administration was registered. Fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different pediatric brain tumors.

Cerebrospinal fluid methylome-based liquid biopsies for accurate malignant brain neoplasm classification.

Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for the clinical management of the main three intra-axial brain tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal to brain tumors, for reliable non-invasive classification that addresses limitations associated with low target abundance in existing approaches. Binomial GLMnet classifiers of tumor type were built, in fifty iterations of 80% discovery sets, using CSF methylomes obtained from 57 BM, GBM, CNSL, and non-neoplastic control patients. Publicly-available tissue methylation profiles (N = 197) on these entities and normal brain parenchyma were used for validation and model optimization. Models reliably distinguished between BM (area under receiver operating characteristic curve [AUROC] = 0.93, 95% confidence interval [CI]: 0.71-1.0), GBM (AUROC = 0.83, 95% CI: 0.63-1.0), and CNSL (AUROC = 0.91, 95% CI: 0.66-1.0) in independent 20% validation sets. For validation, CSF-based methylome signatures reliably distinguished between tumor types within external tissue samples and tumors from non-neoplastic controls in CSF and tissue. CSF methylome signals were observed to align closely with tissue signatures for each entity. An additional set of optimized CSF-based models, built using tumor-specific features present in tissue data, showed enhanced classification accuracy. CSF methylomes are reliable for liquid biopsy-based classification of the major three malignant brain tumor types. We discuss how liquid biopsies may impact brain cancer management in the future by avoiding surgical risks, classifying unbiopsiable tumors, and guiding surgical planning when resection is indicated.

IMMU-40. KINETICS OF DEXAMETHASONE-INDUCED ALTERATIONS OF DIVERSE IMMUNE SUBSETS IN VIVO

Abstract INTRODUCTION Immune therapeutic strategies are ideal for exploiting glial tumor heterogeneity. A limitation to their implementation for intra-axial brain tumors has been corticosteroids. Steroid use is associated with worse progression-free and overall survival when combined with some immunotherapies. Dexamethasone remains first line treatment for vasogenic cerebral edema and a primary therapy for immune-related adverse events secondary to immunotherapies. While used for decades, steroid immunosuppressive effects remain insufficiently characterized. We examined the temporal effects of dexamethasone on an extensive repertoire of immune cell subtypes. METHODS Non-tumor bearing C57BL/6 mice were treated with a onetime dose of 1 mg/kg dexamethasone via gavage, and peripheral blood was sampled at timepoints spanning 1 hour to 7 days. Flow cytometry was performed in triplicate to determine absolute cell counts of circulating B cells, CD8+ T cells (naive/memory), CD4+ T cells (naive/memory/regulatory), NK cells, neutrophils, monocytes, and eosinophils at each timepoint. We examined T cell function at multiple timepoints using an anti-CD3/CD28 bead stimulation assay. RESULTS At 1-hour post-treatment, cell counts across lymphoid subtypes increased. Neutrophils dramatically increased, while the remaining myeloid subtypes began to decrease. NK cells, similarly, were decreased in number. At 4-hours post-treatment all immune subtypes had their lowest circulating counts. There were corresponding increases in CD8+ and CD4+ T cell expansion and proliferation indices at 4-hours. By 24-hours post-treatment, all immune subtypes had recovered to or surpassed pre-treatment counts, except monocytes. By 7 days, the Tregs increased to 186% of pre-treatment counts, the highest of all subtypes, while eosinophils, monocytes, and NK cells never fully recovered to their pre-treatment baselines. CONCLUSIONS Understanding dexamethasone influence on circulating immune cells will inform optimal treatment timing for immunotherapies in brain tumor patients. We are further characterizing transcriptomic changes within immune cell subtypes following dexamethasone administration via population-level RNA sequencing over time.

BIOM-59. NOVEL BIOMARKER DISCOVERY AND DIAGNOSTICS FOR INTRA-AXIAL BRAIN TUMORS, USING CSF PROTEOMICS

Abstract BACKGROUND Invasive brain sampling is typically necessary for reliable diagnosis and prognostication of intra-axial brain tumors but carries risk of morbidity. Liquid biopsy of proximal fluids may mitigate this risk. Through direct contact with the tumor microenvironment and, as an ultra-filtrate of plasma, the cerebrospinal fluid may be the ideal matrix. Reflecting the tumor phenotype, proteomic analyses are critical. Here we identified diagnostic CSF proteomic signatures and putatively novel biomarkers for glioblastoma (GBM), brain metastases (BM), and central nervous system lymphoma (CNSL). METHODS CSF samples were retrospectively retrieved from the Penn State Neuroscience Biorepository and profiled using shotgun proteomics and the MStern approach. Proteomic signatures were identified using machine learning classifiers and survival analyses. RESULTS With as little as 30 µL of CSF, 755 unique proteins were recovered across 73 samples (22 GBM, 17 BM, 14 CNSL, 20 NPH). Proteomic-based classifiers identified malignancy with area under the receiver operating characteristic (AUROC) of 0.94 and distinguished between tumor entities with AUROC ≥0.95. More clinically relevant triplex classifiers, comprised of just 3 proteins, distinguished between tumor entities with AUROC of 0.75-0.89. Novel biomarkers were identified, including GAP43, TFF3 and CACNA2D2, and characterized using single-cell RNA sequencing. DISCUSSION Reliable classification of intra-axial malignancies using low CSF volumes is feasible, allowing for longitudinal tumor surveillance. Based on emerging evidence, upfront implantation of CSF reservoirs in brain tumor patients warrants consideration.

Updates in intraoperative strategies for enhancing intra-axial brain tumor control

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.

Wide Dissection Trans-Sulcal Approach for Resection of Deep Intra-Axial Lesions in Eloquent Brain Areas.

Introduction: Resection of intra-axial tumors (IaT) in eloquent brain regions risks major postoperative neurological deficits. Awake craniotomy is often used to navigate these areas; however, some patients are ineligible for awake procedures. The trans-sulcal approach (TScal) was introduced to reduce parenchymal trauma during tumor resection. We report our experiences utilizing TScal for resection of deep IaT located in eloquent areas. Materials and Methods: This is a single-center retrospective analysis of patients who underwent IaT resection in eloquent areas via TScal from January 2013 to April 2021. Seventeen cases were reviewed, and relevant data was collected. Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) and intraoperative ultrasound was performed in some cases. Results: Seventeen patients (10 males, 7 females) averaging 61.2 years-old (range, 21–76) were included in this study. Average length of stay was 4.8 days, and only 2 patients (11.8%) required hospital readmission within 30 days. Gross total resection (GTR) was achieved in 15 patients (88.2%), while subtotal resection occurred in 2 patients (11.8%). Eleven patients (64.7%) reported full resolution of symptoms, 4 patients (23.5%) reported deficit improvement, and 2 patients (11.8%) experienced no change from their preoperative deficits. No patient developed new permanent deficits postoperatively. Discussion: GTR, preoperative deficit reduction, and complications were comparable to awake craniotomy and other TScal studies. Ancillary intraoperative techniques, such as brain mapping, 5-ALA and intraoperative ultrasound, are afforded by TScal to improve resection rates and overall outcomes. Conclusions: TScal can be an option for patients with deep lesions in eloquent areas who are not candidates for awake surgeries.

Evaluation of a Navigated 3D Ultrasound Integration for Brain Tumor Surgery: First Results of an Ongoing Prospective Study.

The aim of the study was to assess the quality, accuracy and benefit of navigated 2D and 3D ultrasound for intra-axial tumor surgery in a prospective study. Patients intended for gross total resection were consecutively enrolled. Intraoperatively, a 2D and 3D iUS-based resection was performed. During surgery, the image quality, clinical benefit and navigation accuracy were recorded based on a standardized protocol using Likert’s scales. A total of 16 consecutive patients were included. Mean ratings of image quality in 2D iUS were significantly higher than in 3D iUS (p < 0.001). There was no relevant decrease in rating during the surgery in 2D and 3D iUS (p > 0.46). The benefit was rated 2.2 in 2D iUS and 2.6 in 3D iUS (p = 0.08). The benefit remained stable in 2D, while there was a slight decrease in the benefit in 3D after complete tumor resection (p = 0.09). The accuracy was similar in both (mean 2.2 p = 0.88). Seven patients had a small tumor remnant in intraoperative MRT (mean 0.98 cm3) that was not appreciated with iUS. Crucially, 3D iUS allows for an accurate intraoperative update of imaging with slightly lower image quality than 2D iUS. Our preliminary data suggest that the benefit and accuracy of 2D and 3D iUS navigation do not undergo significant variations during tumor resection.