Intra-axial Tumors Research Articles

Delayed Deep White Matter Ischemia After Resection of Gliomas by Awake Surgery

BACKGROUND AND OBJECTIVES: Deep white matter (DWM) is perfused by the medullary arteries from the cortex, and ischemia sometimes occurs after glioma resection. However, the clinical significance of postoperative medullary artery–related ischemia has not been well studied. We retrospectively reviewed cases of delayed DWM ischemia after awake craniotomy to elucidate the clinical characteristics, mechanisms, and management of delayed ischemia. METHODS: We identified 4 cases of intra-axial brain tumors, mainly gliomas, that underwent tumor resection by awake craniotomy at our hospital and developed DWM ischemic symptoms after surgery, despite no worsening of neurological symptoms at the end of surgery. RESULTS: Four patients (3 men and 1 woman) presented with glioblastoma, oligodendroglioma, astrocytoma, and brain metastasis. The median age at surgery was 47.5 years (41-73 years). The tumors were located in the watershed area in the frontal lobe (n = 2) and the parietal lobe (n = 2), all of which were left-sided (n = 4). DWM ischemic symptoms, such as motor dysfunction, aphasia, dysarthria, and dysgraphia, developed at an average of 24 hours (14-48 hours) after resection by awake craniotomy. All 4 patients showed symptom improvement within a week after surgery and completely recovered within a month. CONCLUSION: DWM ischemia is caused by sacrifice of the medullary artery, which feeds the tumor and adjacent brain tissue during tumor resection, and should be considered when delayed aphasia or paralysis occurs postoperatively. These symptoms are often transient and recovery usually occurs. Tumors located in the frontal or parietal lobes, particularly in the watershed area, should be carefully monitored for postoperative ischemia.

TMIC-12. LITT RESULTS IN ROBUST T CELL INFILTRATION WITHIN THE TUMOR MICROENVIRONMENT IN A BRAIN METASTASIS MURINE MODEL

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) is a novel minimally invasive neurosurgical technique used to ablate intra-axial brain tumors with real-time thermometry. The impact of LITT on the brain metastatic tumor microenvironment (TME) is unknown in patients due to limitations of tumor tissue collection post-LITT. The primary objective of this study was to describe the kinetics of immunologic infiltration within the TME in a melanoma brain metastasis model. METHOD: C57BL6 mice underwent intra-cranial implantation of B16F10-OVA tumor cells and treated with LITT using a custom-made murine LITT system developed in our laboratory. The tumors were treated to 42°C (near infra-red 1064 nm DPSS laser system) 7 days post-surgery. Tumors were collected 2 days and 10 days post-LITT for immune-phenotyping using flow cytometry. Blood was collected 6 h and 48 h post-LITT to perform the ELISA for IFN-g and TNF-a. RESULTS LITT treatment triggered a cascade of local infiltration of immune cells at different time points. 2-days post-LITT resulted in increased CD8 T cells (p<0.05), macrophage (p<0.05) and microglia infiltration (p<0.01) within the TME compared to control and sham surgery animals. By 10 days after LITT, significant infiltration by CD8 T cells (p<0.0001) and M1 macrophages (p<0.0001) was observed. The CD8 T cells were T central memory (TCM) and T effector memory (TEM). Moreover, comparison between 2 days and 10 days after LITT revealed significant increase of TEM (p<0.0001) and TCM (p<0.001) 10 days post-LITT. In an ELISA assay, non-significant differences were observed in IFN-g and TNF-a level at 48 h. CONCLUSIONS LITT enhances the recruitment of cytotoxic CD8 T cells within TME in a time-dependent manner. The ability of LITT to recruit TCM and TEM to the TME strongly support its potential therapeutic benefit, especially in the context of immunotherapy.

BIOM-56. HEAT SHOCK PROTEINS PREDICT CLINICAL RESPONSE AND POTENTIATE LOCAL IMMUNOGENICITY AFTER LITT FOR GLIOBLASTOMA

Abstract Glioblastoma (GBM) remains one of the deadliest cancers despite advances in therapies. Laser interstitial thermal therapy (LITT) is a minimally invasive technique used to ablate intra-axial brain tumors. Non-ablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting neoantigen presentation via heat shock proteins (HSPs). HSPs are protein-folding chaperones that present novel intracellular antigens for immune recognition. We investigated HSPs as predictors of local immune response and clinical outcomes of GBM patients undergoing LITT. We conducted immune deconvolution of bulk RNA-sequencing data from The Cancer Genome Atlas to determine the correlation between 97 unique HSPs and tumor infiltration of CD8+, CD4+, B, macrophage, neutrophil, and dendritic cells. We evaluated the association between HSP expression and overall survival (OS). Pre-LITT biopsies from 9 patients (responders and non-responders) were analyzed via immunohistochemistry (IHC) to identify spatial HSP expression. Next-generation sequencing was utilized to validate findings and identify other predictive biomarkers. We identified two HSPs for further investigation: SACS and HSPA5. SACS was associated with improved survival based on TCGA data (14.9 vs. 11 months, HR:1.3, p<0.0001). HSPA5 was associated with worse outcomes (12.1 vs. 15.0 months, HR:0.73, p<0.0001). Immune deconvolution showed HSPA5 positively correlated with dendritic cell infiltration (r=0.50, p=6.1E-27) and SACS with CD8+ infiltration (r=0.31, p=6.8E-11). IHC of 9 patients demonstrated high SACS expression was associated with improved OS (p<0.05) after LITT. Multiplex IHC illustrated that immune cell infiltration was associated with therapeutic response post-LITT. Our ongoing immunohistochemical and genomic analyses aim to clarify the role of HSPs in enhancing immunogenicity in GBM. Further investigation into SACS and immune cell infiltration may reveal how hyperthermia via LITT improves response through neoantigen presentation.

NIMG-43. INFARCTION RADIOLOGICALLY MIMICKING INTRA-AXIAL BRAIN TUMORS

Abstract There are several reports of brain lesions that radiologically mimicking the brain tumors. The abscess is representative lesion of resembling the intra-axial tumors in brain MRI. However, cerebral infarction is not a common lesion that resembles a brain tumor and can be easily distinguished from a brain tumor in MRI. Here, we represented the two cases of pathologically diagnosed infarction that radiologically suspected gliomas. A 67-year-old man presented with left side weakness and memory impairment. Brain MRI revealed the rim enhancing lesion radiologically suspected glioma. Navigation guided biopsy was performed and final pathological diagnosis was subacute infarction. A-41-year-old man represented the right side weakness. MRI showed the enhancing nodular lesion with perilesional edema. Surgical excision was performed and pathological diagnosis was infarction. Although advancement of brain imaging techniques, it is difficult to accurately discriminate the intracerebral lesions utilizing the MRI. Further comprehensive study should be executed for more precise differentiation of infarction and brain tumors.

Pathological tissue changes in brain tumors affect the pH-sensitivity of the T1-corrected apparent exchange dependent relaxation (AREX) of the amide protons.

Measuring the intracellular pH (pHi) is of interest for brain tumor diagnostics. Common metrics of CEST imaging like the amide proton transfer-weighted (APTw) MTRasym are pHi sensitive and allow differentiating malignant tumor from healthy tissue. Yet, the image contrast also depends on additional magnetization transfer effects and T1. In contrast, the apparent exchange-dependent relaxation (AREX) provides a T1 corrected exchange rate of the amide protons. As AREX still depends on amide proton density, its pHi sensitivity remains ambiguous. Hence, we conducted this study to assess the influence of pathologic tissue changes on the pHi sensitivity of AREX in vivo. Patients with newly diagnosed intra-axial brain tumors were prospectively recruited and underwent conventional MRI, quantitative T1 relaxometry, APT-CEST and 31P-MRS on a 3T MRI scanner. Tumors were segmented into contrast-enhancing tumor (CE), surrounding T2 hyperintensity (T2-H) and contralateral normal appearing white matter (CNAWM). T1 mapping and APT-CEST metrics were correlated with 31P-MRS-derived pHi maps (Pearson's correlation). Without differentiating tissue subtypes, pHi did not only correlate significantly with MTRasym (r= 0.46) but also with T1 (r= 0.49). Conversely, AREX only correlated poorly with pHi (r= 0.17). Analyzing different tissue subtypes separately revealed a tissue dependency of the pHi sensitivity of AREX with a significant correlation (r= 0.6) in CNAWM and no correlation in T2-H or CE (r= -0.11/-0.24). CE showed significantly increased MTRasym, pHi, and T1 compared with CNAWM (p< 0.001). In our study, the pHi sensitivity of AREX was limited to CNAWM. The lack of sensitivity in CE and T2-H is probably attributable to altered amide and water proton concentrations in these tissues. Conversely, the correlation of pHi with MTRasym may be explained by the coincidental contrast increase through increased T1 and amide proton density. Therefore, limited structural deviations from CNAWM might be a perquisite for the use of CEST contrasts as pHi-marker.

TRLR-01 THE PROGNOSTIC UTILITY OF TEMPORALIS MUSCLE THICKNESS MEASURED ON MAGNETIC RESONANCE SCANS IN PATIENTS WITH INTRA-AXIAL MALIGNANT BRAIN TUMOURS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract OBJECTIVE Sarcopenia is associated with worsened outcomes in solid cancers. Temporalis muscle thickness (TMT) has emerged as a measure of sarcopenia. Hence, this study aims to evaluate the relationship between TMT and outcome measures in patients with malignant intra-axial neoplasms. METHODS Following the PRISMA guidelines, we systematically searched PubMed, Embase, Scopus, and Cochrane databases for relevant studies from inception until June 17, 2022. Event ratios with 95% confidence intervals (CI) were analyzed using the RevMan 5.4 software. Where meta-analysis was impossible, vote counting was used to determine the effect of TMT on outcomes. The GRADE framework was used to determine the certainty of the evidence. RESULTS Four outcomes were reported for three conditions across 17 studies involving 4430 patients. Glioblastoma: thicker TMT was protective for overall survival (OS) (HR 0.59; 95% CI 0.46–0.76) (GRADE low), progression-free survival (PFS) (HR 0.40; 95% CI 0.26–0.62) (GRADE high), and early discontinuation of treatment (OR 0.408; 95% CI 0.168–0.989) (GRADE high); no association with complications (HR 0.82; 95% CI 0.60–1.10) (GRADE low). Brain Metastases: thicker TMT was protective for OS (HR 0.73; 95% CI 0.67–0.78) (GRADE moderate); no association with PFS (GRADE low). Primary CNS Lymphoma: TMT was protective for overall survival (HR 0.34; 95% CI 0.19–0.60) (GRADE moderate) and progression-free survival (HR 0.23; 95% CI 0.09–0.56) (GRADE high). CONCLUSION TMT has significant prognostic potential in intra-axial malignant neoplasms, showing a moderate to high certainty for its association with outcomes following GRADE evaluation. This will enable shared decision-making between patients and clinicians.

ID: 344300 Percutaneous Spinal Cord Stimulation for Treatment of Chronic Neuropathic Pain Syndrome associated with Intra-axial Neoplasm

ID: 344300 Percutaneous Spinal Cord Stimulation for Treatment of Chronic Neuropathic Pain Syndrome associated with Intra-axial Neoplasm

Sonodynamic therapy for adult-type diffuse gliomas: past, present, and future.

Intra-axial brain tumors persist as significant clinical challenges. Aggressive surgical resection carries risk of morbidity, and the blood-brain barrier (BBB) prevents optimal pharmacological interventions. There is a clear clinical demand for innovative and less invasive therapeutic strategies for patients, especially those that can augment established treatment protocols. Focused ultrasound (FUS) has emerged as a promising approach to manage brain tumors. Sonodynamic therapy (SDT), a subset of FUS, utilizes sonosensitizers activated by ultrasound waves to generate reactive oxygen species (ROS) and induce tumor cell death. This review explores the historical evolution and rationale behind SDT, focusing on its mechanisms of action and potential applications in brain tumor management. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Preclinical studies have demonstrated the efficacy of various sonosensitizers, including 5-aminolevulinic acid (5-ALA), fluorescein, porphyrin derivatives, and nanoparticles, in conjunction with FUS for targeted tumor therapy and BBB disruption. Clinical trials have shown promising results in terms of safety and efficacy, although further research is needed to fully understand the potential adverse effects and optimize treatment protocols. Challenges such as skull thickness affecting FUS penetration, and the kinetics of BBB opening require careful consideration for the successful implementation of SDT in clinical practice. Future directions include comparative studies of different sonosensitizers, optimization of FUS parameters, and exploration of SDT's immunomodulatory effects. SDT represents a promising frontier in the treatment of aggressive brain tumors, offering hope for improved patient outcomes.

Accuracy of Intra-Axial Brain Tumor Characterization in the Emergency MRI Reports: A Retrospective Human Performance Benchmarking Pilot Study.

Demand for emergency neuroimaging is increasing. Even magnetic resonance imaging (MRI) is often performed outside office hours, sometimes revealing more uncommon entities like brain tumors. The scientific literature studying artificial intelligence (AI) methods for classifying brain tumors on imaging is growing, but knowledge about the radiologist's performance on this task is surprisingly scarce. Our study aimed to tentatively fill this knowledge gap. We hypothesized that the radiologist could classify intra-axial brain tumors at the emergency department with clinically acceptable accuracy. We retrospectively examined emergency brain MRI reports from 2013 to 2021, the inclusion criteria being (1) emergency brain MRI, (2) no previously known intra-axial brain tumor, and (3) suspicion of an intra-axial brain tumor on emergency MRI report. The tumor type suggestion and the final clinical diagnosis were pooled into groups: (1) glial tumors, (2) metastasis, (3) lymphoma, and (4) other tumors. The final study sample included 150 patients, of which 108 had histopathological tumor type confirmation. Among the patients with histopathological tumor type confirmation, the accuracy of the MRI reports in classifying the tumor type was 0.86 for gliomas against other tumor types, 0.89 for metastases, and 0.99 for lymphomas. We found the result encouraging, given the prolific need for emergency imaging.

Intraoperative ultrasound and magnetic resonance comparative analysis in brain tumor surgery: a valuable tool to flatten ultrasound's learning curve.

Intraoperative ultrasound (IOUS) is a profitable tool for neurosurgical procedures' assistance, especially in neuro-oncology. It is a rapid, ergonomic and reproducible technique. However, its known handicap is a steep learning curve for neurosurgeons. Here, we describe an interesting postoperative analysis that provides extra feedback after surgery, accelerating the learning process. We conducted a descriptive retrospective unicenter study including patients operated from intra-axial brain tumors using neuronavigation (Curve, Brainlab) and IOUS (BK-5000, BK medical) guidance. All patients had preoperative Magnetic Resonance Imaging (MRI) prior to tumor resection. During surgery, 3D neuronavigated IOUS studies (n3DUS) were obtained through craniotomy N13C5 transducer's integration to the neuronavigation system. At least two n3DUS studies were obtained: prior to tumor resection and at the resection conclusion. A postoperative MRI was performed within 48h. MRI and n3DUS studies were posteriorly fused and analyzed with Elements (Brainlab) planning software, permitting two comparative analyses: preoperative MRI compared to pre-resection n3DUS and postoperative MRI to post-resection n3DUS. Cases with incomplete MRI or n3DUS studies were withdrawn from the study. From April 2022 to March 2024, 73 patients were operated assisted by IOUS. From them, 39 were included in the study. Analyses comparing preoperative MRI and pre-resection n3DUS showed great concordance of tumor volume (p < 0,001) between both modalities. Analysis comparing postoperative MRI and post-resection n3DUS also showed good concordance in residual tumor volume (RTV) in cases where gross total resection (GTR) was not achieved (p < 0,001). In two cases, RTV detected on MRI that was not detected intra-operatively with IOUS could be reviewed in detail to recheck its appearance. Post-operative comparative analyses between IOUS and MRI is a valuable tool for novel ultrasound users, as it enhances the amount of feedback provided by cases and could accelerate the learning process, flattening this technique's learning curve.

Establishing the utility of multi-platform liquid biopsy by integrating the CSF methylome and proteome in CNS tumours.

Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, it is increasingly recognized that multi-omic molecular approaches are a powerful avenue through which to understand complex and heterogeneous disease biology. We hypothesize that merging these two promising frontiers of cancer research will improve the discriminatory capacity of current models and allow for improved clinical utility. We have compiled a cohort of patients with glioblastoma, brain metastasis, and primary central nervoussystem lymphoma. Cell-free methylated DNA immunoprecipitation (cfMeDIP) and shotgun proteomic profiling wasobtained from the cerebrospinal fluid (CSF) of each patient and used to build tumour-specific classifiers. We show that the DNA methylation and protein profiles of cerebrospinal fluid can be integrated to fully discriminate lymphoma from its diagnostic counterparts with perfect AUC of 1 (95% confidence interval 1-1) and 100% specificity, significantly outperforming single-platform classifiers. We present the most specific and accurate CNS lymphoma classifier to date and demonstrates the synergistic capability of multi-platform liquid biopsies. This has far-reaching translational utility for patients with newly diagnosed intra-axial brain tumours.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent adifferential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. We retrospectively analyzed the preoperative imaging of 45patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). Thirty-nine patients were classified as having an ependymoma, 35with aZFTA fusion and four with aYAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), acystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Supraorbital Approaches for Anterior Skull Base and Parasellar Lesions: Insights From a Single-Center Experience.

Modern neurosurgery has undergone significant evolution to include minimally invasive procedures, with the supraorbital approach (SOA) being a prime example. In this study, we aim to explore the surgical techniques and outcomes of this approach in the surgical treatment of frontal lobe, anterior skull base, and parasellar lesions. This study included 33 patients aged 36-83 years who underwent surgery using the SOA for lesions in the inferior frontal lobe, anterior skull base, and parasellar area between 2015 and 2024. There were 25 cases of meningioma, 2 cases of brain abscess, 2 cases of glioma, and one case each of craniopharyngioma, hemangioma, metastasis, and Rathke's cleft cyst. The medical data and follow-up results were retrospectively analyzed. The mean size of lesion was 3.38±3.05 cm. The mean follow-up period was 48.8 months. Gross total resection was achieved in 25 patients (75.8%). There were no perioperative deaths, cases of cerebrospinal fluid rhinorrhea, or infections. Two cases of morbidity were reported as complications: one case of delayed intracerebral hemorrhage and one case of infarction due to vascular injury. All patients exhibited satisfactory cosmetic results. In comparison to the conventional pterional approach, the SOA represents a safe and effective keyhole method for the removal of both extra-axial and intra-axial skull base tumors. This is particularly beneficial for lesions in the orbitofrontal region and parasellar area, as it allows for minimal disruption of normal brain parenchyma. Moreover, the SOA promotes a swift recovery and short hospital stay. Additionally, the SOA yields superior cosmetic results, including the prevention of temporalis muscle atrophy.

The unseen impact - a deep dive into neurocognitive impairment among patients with intracranial meningiomas: a comprehensive systematic review of the literature.

Meningiomas are the most common intracranial tumors, predominantly affecting adults, with a higher incidence in female and elderly populations. Despite their prevalence, research on neurocognitive impairment in meningioma patients remains limited compared to intra-axial tumors such as gliomas. We conducted a comprehensive systematic review of the current literature on neurocognitive outcomes in meningioma patients pre- and post-surgery. Our review revealed significant disparities in reported neurocognitive outcomes, with prospective studies suggesting tumor-related factors as the primary contributors to postoperative deficits, while retrospective studies imply surgical intervention plays a significant role. Regardless of study design or specifics, most studies lack baseline preoperative neurocognitive assessments and standardized protocols for evaluating neurocognitive function. To address these gaps, we advocate for standardized neurocognitive assessment protocols, consensus on neurocognitive domains to be targeted in this population by tailored test batteries, and more prospective studies to elucidate correlations between tumor characteristics, patient attributes, surgical interventions, neurocognitive status, and planning for implementing tailored neurocognitive rehabilitation strategies early in the postoperative course which is crucial for achieving optimal long-term neurocognitive outcomes and enhancing patients' quality of life.

QOL-42. ANALYSIS OF LATE EVENTS AFTER RADIATION THERAPY FOR PRIMARY PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Late events after radiation therapy for primary brain tumors consist of secondary malignant neoplasms (SMN) and tumor recurrences. The incidence and biology of late events are not very well described. Therefore, we aimed to identify late events in our institutional cohort and describe their biology. METHODS A retrospective chart review of all irradiated pediatric brain tumor patients treated between 2000 and 2015 at our institution was performed to obtain demographics and clinical data of late events. Late events were defined as intracranial intraaxial SMN or tumor recurrence occurring later than 3 years after radiation therapy. A whole-genome methylation array was employed to identify the methylation class of the late event. RESULTS In the observed period, 267 patients received some form of cranial radiotherapy for primary brain tumor; high-grade glioma (HGG, n=66), medulloblastoma (n=74), ependymoma (n=50), germ-cell tumors (GCT, n=22), low-grade glioma (LGG, n=24), and other diagnoses (n=31). Out of the 174 patients who were alive and without an event after 3 years from the radiation therapy, 30 developed late events (16.8%), and 27 of them were histologically verified. Verified late events consisted of 8 SMNs (29.6%) and 19 primary tumor recurrences. SMNs were mainly radiation-induced gliomas (RIG, n=7) and one atypical teratoid/rhabdoid tumor (ATRT) after craniopharyngioma. All RIG tumors clustered with the “pediatricHGG_RTK1” methylation class. Tumor recurrences consisted of medulloblastomas (Group 4 and Wnt), ependymomas (PFA and ST_ZFTA), GCTs, gliomas (one NF1-associated HGG, one H3-altered thalamic glioma, one diffuse astrocytoma with BRAF-V600E mutation), and craniopharyngiomas. The overall survival rate 5 years after a late event was 39.7%, with a worse survival rate for SMN patients (14.3%) compared to those with recurrences (44.9%) (p=0.05). CONCLUSIONS Late events affected 16.8% of long-term survivors. Strikingly, SMNs represented almost 30% of late events and were associated with a very poor prognosis.

The prognostic utility of temporalis thickness measured on MRI scans in patients with intra-axial malignant brain tumours: a systematic review and meta-analysis

Sarcopenia is associated with worsened outcomes in solid cancers [1].Temporalis muscle thickness (TMT) has emerged as a measure of sarcopenia[2]. Hence, this study aims to evaluate the relationship between TMTand outcome measures in patients with malignant intra-axial neoplasms.We searched Medline, Embase, Scopus, and Cochrane databases for relevantstudies. Event ratios with 95% confidence intervals (CI) were analysedusing the RevMan 5.4 software. Where meta-analysis was impossible, votecounting was used to determine the effect of TMT on outcomes. TheGRADE framework was used to determine the certainty of the evidence. Four outcomes were reported for three conditions across 17 studiesinvolving 4430 patients. Glioblastoma: thicker TMT was protective foroverall survival (OS) (HR 0.59; 95% CI 0.46–0.76) (GRADE low), progressionfree survival (PFS) (HR 0.40; 95% CI 0.26–0.62) (GRADE high),and early discontinuation of treatment (OR 0.408; 95% CI 0.168–0.989)(GRADE high); there was no association with complications (HR 0.82;95% CI 0.60–1.10) (GRADE low). Brain Metastases: thicker TMTwas protective for OS (HR 0.73; 95% CI 0.67–0.78) (GRADE moderate);there was no association with PFS (GRADE low). Primary CNSlymphoma: TMT was protective for overall survival (HR 0.34; 95%CI 0.19–0.60) (GRADE moderate) and progression free survival (HR0.23; 95% CI 0.09–0.56) (GRADE high).Across various intracranial intra-axial malignancies, patients withthicker TMT have better survival outcomes and are less prone to discontinuingtreatment secondary to drug toxicity. TMT has the potential tobe a valuable prognostic tool for risk-benefit considerations in the managementof these patients.

Evaluation of an ultrasound-guided freeze-core biopsy system for canine and feline brain tumors.

To determine if a single brain biopsy utilizing a freeze-core needle harvest system Cassi II under ultrasound guidance provides a diagnostic sample; to evaluate the technique's efficacy in procuring diagnostic samples in comparison with "open" surgical biopsies; and to describe intraoperative complications associated with the technique. Experimental clinical study. Seventeen dogs and four cats with magnetic resonance imaging (MRI) diagnoses of readily surgically accessible intracranial masses. Immediately prior to surgical biopsy (SB), freeze-core biopsy (FCB) sample was obtained from each patient under ultrasound guidance. Histopathology results from single FCB samples were found to be in 100% agreement with the SB samples. Freezing artifact was minimal and did not interfere with histopathologic interpretation. There were no intraoperative complications specifically attributable to the use of the FCB system. Based on the results of this small experimental study, the FCB system is expected to safely yield diagnostic quality intracranial masses biopsy specimens. This system has the potential of obtaining diagnostic biopsies of more deeply seated brain lesions (i.e., intra-axial tumors considered inaccessible or with large risks/difficulties by standard surgical means) which would provide a definitive diagnosis to guide appropriate therapy.

491 Scalp Incisions With Stairstep Pericranial Edges to Minimize Sequalae of Poor Wound Healing in Supratentorial Brain Tumor Surgery

INTRODUCTION: Wound healing problems are especially prevalent in craniotomies for intra-axial brain tumors as patients often require radiation, chemotherapy, and chronic steroids. All surgeons have postoperative patients with poor skin healing (i.e., excessive scabbing) at follow up, some of whom progress to infections that may involve the bone graft or hardware. While newer techniques like minimally invasive approaches and routine vancomycin powder use have helped overall complication rates, poor skin healing remains a frustratingly persistent cause of morbidity. METHODS: Ninety-one consecutive patients underwent supratentorial, intra-axial brain tumor surgery with a single surgeon at a single institution using this technique. Patient demographics, pathology, adjuvant interventions, and other independent risk factors were analyzed. RESULTS: No wound-related complications requiring readmission, intravenous antibiotics, or reoperation were encountered at a median 3-month follow up. There were also no surgical site infections, dehiscences, or CSF leaks. Fifty-one patients (57.3%) had postoperative radiotherapy, eighty-five patients (93.4%) had perioperative steroids, and fifty-six patients (61.5%) had postoperative chemotherapy. Six patients (6.5%) had concerns for poor initial scalp healing at routine follow up and were placed on a short course of oral antibiotics prophylactically. None (0%) of these individuals progressed to infection or required further intervention. One other patient developed a shunt infection in this interval that required removal unrelated to the craniotomy site. CONCLUSIONS: Here we outline the principles and demonstrate the execution of stairstep pericranial edges in supratentorial brain surgery. This technique, designed with plastic surgeons, provides an intact, vascularized layer of pericranium beneath the incision and over the bone graft/hardware to optimize wound healing and prevent morbid sequelae in inevitable cases of poor initial skin healing.

Abstract 1022: Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma

Abstract Background: The diagnosis of intra-axial brain tumors requires histopathological examination of tissue obtained by neurosurgery in current clinical practice, which comes with inherent risks. Some patients, particularly those with primary CNS lymphoma (PCNSL), only undergo surgery to obtain a diagnosis and do not derive any therapeutic benefit from surgical resection or debulking. Less-invasive techniques for diagnosis, such as liquid biopsy, therefore provides an opportunity to mitigate surgical risk in these patients. Methods: Patients with histopathology confirmed glioblastoma (GBM, IDH wild type), brain metastases (BM), and PCNSL with accompanying cerebrospinal fluid (CSF) samples were included in our study. Cell-free DNA methylation profiling and shotgun proteomics were obtained for all patients and used to train classifiers to distinguish each tumour entity from others. Specifically, binomial elastic net regression models were built by combining both data modalities using established early and late integration paradigms and performance was compared to classifiers built from individual data types alone. Each model was repeated 100 fold and performance assessed on an untouched testing subset. Results: Our cohort includes 20 patients with GBM, 17 with BM, and 14 with PCNSL, each with matching CSF cell-free DNA methylation and shotgun proteomic profiling. We show that these data can be integrated to fully discriminate PCNSL from its major diagnostic counterparts with a perfect median AUC of 1.00 (95% CI 1-1) and 100% specificity. Integrated "lymphoma vs other" models significantly outperform models trained on methylation or protein data alone, though the same dramatic improvement was not demonstrated in GBM or BM, suggesting synergistic biological information is specific to lymphoma. Conclusions: There is a critical need to diagnose patients with intra-axial tumours, particularly PCNSL, without relying on invasive and costly surgery. We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has the potential for immediate clinical utility, eliminating the need for biopsy in an important subset of these patients. Citation Format: Alex P. Landry, Jeffrey A. Zuccato, Vikas Patil, Mathew Voisin, Justin Z. Wang, Yosef Ellenbogen, Chloe Gui, Andrew Ajisebutu, Farshad Nassiri, Gelareh Zadeh. Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1022.

Serum Interleukin-38 and Tumor-Infiltrating Lymphocytes in Primary Brain Tumors.

Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. However, its biological roles in brain tumors are not well defined. To assess the serum levels of IL-38 and the percentages of TILs in the tumor tissues of patients with primary brain tumors and to determine their associations with the pathological features of the disease. IL-38 was evaluated in sera using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E)-stained sections were scored to determine the percentages of TILs in four different areas: the invasive margin, central tumor, perivascular and perinecrotic areas. IL-38 serum levels were significantly higher in low- and high-grade tumors than in healthy individuals, meanwhile, its levels remained consistent between these two grades. Although no significant difference was found in IL-38 serum levels between different histological subtypes of brain tumors, its levels were significantly higher in intra-axial brain tumors than in extra-axial ones. Additionally, a significant positive correlation was observed between serum levels of IL-38 and tumor size in patients with low-grade tumors. TILs were detected in at least one of the four examined areas; however, no statistically significant correlation was found between IL-38 levels and TILs. Our data may suggest a connection between IL-38 and immune suppression and tumor progression in primary brain tumors. Further investigation is needed to uncover the role of IL-38 in the brain tumor microenvironment.