Brain Tumor Biopsies Research Articles

In situ optical feedback in brain tumor biopsy - a multipara-metric analysis

Abstract Introduction Brain tumor needle biopsy interventions are inflicted with non-diagnostic or biased sampling in up to 25% and hemorrhage, including asymptomatic cases, in up to 60%. To identify diagnostic tissue and sites with increased microcirculation, intraoperative optical techniques have been suggested. The aim of this study was to investigate the clinical implications of in situ optical guidance in frameless navigated tumor biopsies. Methods Real-time feedback on protoporphyrin IX (PpIX) fluorescence, microcirculation, and gray-whiteness was given before tissue sampling (272 positions) in 20 patients along 21 trajectories in total. The primary variables of investigation were fluorescence in relation to neuropathological findings and gadolinium (Gd) enhancement, increased cerebral microcirculation in relation to bleeding incidence, number of trajectories, and impact on operation time. Results PpIX fluorescence was detected in Glioblastoma IDH-wildtype CNS WHO grade 4 (n=12), Primary diffuse large B-cell lymphoma (n=3), astrocytoma IDH-mutated CNS WHO grade 4 (n=1) (Ki67 indices ≥15%). For two patients, no PpIX fluorescence or Gd was found, although samples contained tumorous tissue (Ki67 index 6%). Increased microcirculation was found along nine trajectories (34 sites), located in cortical, tumorous, or tentorium regions. Postoperative bleedings (n=10, nine asymptomatic) were related to skull opening or tissue sampling. The present study strengthens the proposed independence from intraoperative neuropathology as PpIX fluorescence is detected. Objective real-time feedback resulted in fewer trajectories compared to previous studies indicating reduced operation time. Conclusions The integrated optical guidance system provides real-time feedback in situ, increasing certainty and precision of diagnostic tissue before sampling during frameless brain tumor biopsies.

EXPLORING MOLECULAR LINKS IN BRAIN TUMOUR BIOPSY TISSUES AND ALZHEIMER’S DISEASE

Abstract AIMS Generate and identify putative targets in the SORL1-network by mining online databases. Analyse 21 FFPE human brain tumour biopsy tissues through transcriptome sequencing performed by CeGaT (Tübingen, Germany) to explore differentially expressed genes. These biopsy samples are from consenting patients in association with Brain Tumour North West (BTNW) and the Royal Preston Hospital. METHOD Group comparisons are performed with the control and cancerous sample groups (low-grade glioma staying low, low-grade glioma becoming high and high-grade staying high). Further analysis involves comparing section and resection from the same patient for each cancer tissue group. Samples are explored on four different bioinformatic levels and sequenced on the Illumina platform. In Level 1 the data is demultiplexed and trimmed and in Level 2 trimmed reads are additionally mapped. Level 3 provides insights into the cell’s metabolic state and Level 4 performs several group comparisons. RESULTS Gain insights into differentially expressed genes’ presence in biopsy tissues from different stages of brain cancer, expression levels and links to clinical characteristics. Bioinformatic analysis provides data on quality control of the starting material, library preparation, sequencing parameters, and the Q30 value of the sequencing. CONCLUSION The analysis demonstrates molecular links in the SORL1-network in tissue from section and resection from a patient cohort to better understand disease recurrent and progression. Prospective bioinformatic work would explore interactions between significant targets identified to create a curated network that could predict druggable targets in gliomas.

The implication of liquid hemostatic matrices to prevent hemorrhages during stereotactic biopsy of brain tumors

The implication of liquid hemostatic matrices to prevent hemorrhages during stereotactic biopsy of brain tumors

Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene

Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains. In HEK293 cells, constitutive active TrkB kinase and an intracellular NTRK2-fusion oncogene (SQSTM1-NTRK2) reduced actin filopodia dynamics, phosphorylated FAK, and altered the cell morphology. Atypical cellular responses could be mimicked with the intracellular kinase domain, which did not activate the Trk-associated MAPK/ERK pathway. In glioblastoma-like U87MG cells, expression of TrkB or SQSTM1-NTRK2 reduced cell motility and caused drastic changes in the transcriptome. Clinically approved Trk inhibitors or mutating Y705 in the kinase domain, blocked the cellular effects and transcriptome changes. Atypical signaling was also seen for TrkA and TrkC. Moreover, hallmarks of atypical pTrk kinase were found in biopsies of Nestin-positive glioblastoma. Therefore, we suggest Western blot-like immunoassay screening of NTRK-related (brain) tumor biopsies to identify patients with atypical panTrk or phosphoTrk signals. Such patients could be candidates for treatment with NTRK inhibitors such as Larotrectinhib or Entrectinhib.

Value of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in predicting hospital mortality for postoperative brain tumor patients in intensive care units in Japan: A retrospective case-control study

ObjectiveAcute Physiology and Chronic Health Evaluation II (APACHE II) is based on the data of intensive care unit (ICU) patients and often correlates with disease severity and prognosis. However, no prognostic predictors exist based on ICU admission data for patients with brain tumors, and no studies have reported an association between APACHE II and prognosis in patients with brain tumors. The Japanese Intensive Care Patients Database (JIPAD) was established to improve the quality of care delivered in intensive care medicine in Japan. We used JIPAD to examine factors associated with in-hospital mortality based on available data of postoperative patients with brain tumors admitted to the ICU. MethodsPatients aged ≥16 years enrolled in JIPAD between April 2015 and March 2018 after surgical brain tumor resection or biopsy of brain tumors. We examined factors related to outcomes at discharge based on blood tests and medical procedures performed during ICU admission, tumor type, and APACHE II score. ResultsAmong the 1454 patients (male:female ratio: 1:1.1, mean age: 62 years) in the study, 32 (2.2 %) died during hospital stay. In multivariate analysis, male sex (odds ratio [OR] 2.70, [95 % confidence interval, CI 1.22–6.00]), malignant tumor (OR 2.51 [95 % CI 1.13–5.55]), and APACHE II score ≥15 (OR 2.51 [95 % CI 3.08–14.3]) were significantly associated with in-hospital mortality. ConclusionBy picking up cases with a high risk of in-hospital death at an early stage, it is possible to improve methods of treatment and support for the patient's family.

LGG-16. BRAFV600K LOW-GRADE GLIOMA EMERGENCE DURING THERAPY FOR BRAFV600E HIGH-GRADE GLIOMA

Abstract BACKGROUND BRAFV600E mutations are prevalent in pediatric brain tumors, constituting 20% of low-grade and 5% of high-grade gliomas. Other single-nucleotide substitutions in BRAF are described in adult cancers but rarely in pediatric brain tumors. Our case sheds light on a unique scenario—a patient with a BRAF-mutated high-grade spinal glioma who later developed slowly progressive intracranial low-grade glioma, subsequently undergoing rapid high-grade transformation. METHODS Case Report RESULTS Our patient initially presented as a thirteen-year-old male with a two-month history of progressive bilateral hand weakness/paresthesias. Spine MRI revealed a fusiform expansile intramedullary neoplasm from C3-T2, brain MRI was negative. Biopsy showed an anaplastic astrocytoma with BRAFV600E mutation and MYC-N amplification. Initial treatment included proton radiation and a 2-year course of Dabrafenib/Trametinib, maintaining disease stability. After four months off therapy, he developed local progression, and re-staging brain MRI showed new cerebellar/supratentorial lesions. Dabrafenib/Trametinib was re-started until progression two years later. He developed hydrocephalus and underwent ETV and brain tumor biopsy, which revealed a low-grade glioma with BRAFV600K mutation. At this point, Dabrafenib/Trametinib continued for another 1.5 years; he exhibited slow progression of the brain tumors before a cerebellar lesion developed rapid progression. He had GTR of the rapid-growing lesion, and pathology reported a Grade 4 invasive astrocytoma harboring BRAFV600E, two VUS MTOR mutations, and MGMT promoter methylation. Current treatment involves radiation therapy concurrent with temozolomide. CONCLUSIONS While combinatorial Dabrafenib/Trametinib is effective in glioma therapy, resistance and progression challenges persist. Our case presents a unique manifestation—a patient with a spinal high-grade glioma with BRAFV600E who developed a secondary low-grade glioma with BRAFV600K in the brain, which, after several years, transformed into a high-grade glioma. Future research is crucial for comprehending the intricate role of BRAF mutations in pediatric gliomas, paving the way for improved patient outcomes.

NURS-23. THE ROLE OF THE ADVANCED PRACTICE PROVIDER IN THE PAIRED NORMAL SPECIMEN PROCESS AT A TERTIARY CARE CENTER

Abstract BACKGROUND Paired tumor - normal specimen testing is standard of care to improve the timing and knowledge of genetic variations present in the brain tumor cell and germline. A new process was developed to ensure the paired normal specimen (PNS) testing was completed. METHODS The Neuro-Oncology Advanced Practice Provider (APP) is integral in the process of ordering and obtaining the PNS. RESULTS In the last 15 months, this tertiary care center has performed more than 90 pediatric brain tumor biopsies and/or resections. APPs identify patient surgery dates via the neurosurgery calendar. On the day of surgery a PNS is ordered for the Solid Tumor panel (predetermined by pathology and neuro-oncology) and “Include germline variant resolution information if applicable?” is answered as “No”. The laboratory runs the next generation sequencing (NGS) on PNS and tumor but the findings remain blinded until a second order is placed to “unblind” the specimen. By doing so, the treating physician collaborates with a genetics counselor prior to discussing with the family. Initial difficulty included patient identification, ordering, and collecting PNS. The APPs developed a shared list with patient identifiers, surgery date, order and collection date of PNS which has ensured less than 5% of PNS have been missed. Challenges include weekend surgeries, APPs out of office, and communication to nursing to collect PNS. Updated protocol includes ordering PNS, messaging shift nurse with order explanation and request to collect. Additionally, the pathology team now messages the APPs if a PNS is not submitted and the tumor is undergoing NGS. CONCLUSIONS Comprehensive processes ensure that paired normal – tumor testing is completed in a timely manner and during the same admission with surgery to ensure better insurance coverage and less cost to families, as well as earlier results of somatic and germline variants.

Role of Machine Learning in Liquid Biopsy of Brain Tumours

Liquid biopsy has multiple benefits and is used extensivelyin other fields of oncology, but its role in neuro-oncologyhas been limited so far. Multiple tumour-derived materialslike circulating tumour cells (CTCs), tumour-educatedplatelets (TEPs), cell-free DNA (cfDNA), circulating tumourDNA (ctDNA), and miRNA are studied in CSF, blood (plasma,serum) or urine. Large and complex amounts of data fromliquid biopsy can be simplified by machine learning usingvarious algorithms. By using this technique, we candiagnose brain tumours and differentiate low versus highgradeglioma and true progression frompseudo-progression. The potential of liquid biopsy in braintumours has not been extensively studied, but it has abright future in the coming years. Here, we present aliterature review on the role of machine learning in liquidbiopsy of brain tumours.

Focused Ultrasound-Enhanced Liquid Biopsy: A Promising Diagnostic Tool for Brain Tumor Patients.

The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood-brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms "brain tumors", "liquid biopsy", "FUS" and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice.

Diagnostic yield of postmortem brain examination following premortem brain biopsy for neoplastic and nonneoplastic disease.

Medical autopsies have decreased in frequency due in part to advances in radiological techniques and increased availability of molecular and other ancillary testing. However, premortem diagnosis of CNS disease remains challenging; while ∼90% of brain tumor biopsies are diagnostic, only 20%-70% of biopsies for presumed nonneoplastic disease result in a specific diagnosis. The added benefits of performing an autopsy following surgical brain biopsy are not well defined. A retrospective analysis was performed of patients who underwent brain biopsy and autopsy at Brigham and Women's Hospital from 2003 to 2022. A total of 135 cases were identified, including 95 (70%) patients with primary CNS neoplasms, 16 (12%) with metastatic tumors, and 24 (18%) with nonneoplastic neurological disease. Diagnostic concordance between biopsy and autopsy diagnosis was excellent both for primary CNS neoplasms (98%) and metastatic tumors (94%). Conversely, patients with nonneoplastic disease received definitive premortem diagnoses in 7/24 (29%) cases. Five (21%) additional patients received conclusive diagnoses following autopsy; 8 (33%) received a more specific differential diagnosis compared to the biopsy. Overall, autopsy confirmed premortem diagnoses or provided new diagnostic information in 131/135 (97%) cases, highlighting the value in performing postmortem brain examination in patients with both neoplastic and nonneoplastic diseases.

Neuropathological Applications of Microscopy with Ultraviolet Surface Excitation (MUSE): A Concordance Study of Human Primary and Metastatic Brain Tumors.

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA.

Microsurgical ventriculostomy of the third ventricle with access through a burrhole in the treatment of midly located deep-seated brain tumors

Currently, endoscopic third ventriculostomy and simultaneous biopsy of deep midline brain tumors are a generally accepted option in neurooncology. Nevertheless, effectiveness of this surgery and diagnostic accuracy of biopsy are not without drawbacks. An alternative to endoscopic surgery may be simultaneous microsurgical third ventriculostomy and biopsy of deep midline tumors. To evaluate effectiveness and safety of burr hole microsurgical third ventriculostomy in the treatment of deep midline brain tumors. We used transcortical (25 cases) and transcallosal (8 cases) approaches for microsurgical third ventriculostomy. Initially scheduled biopsy was performed in 19 cases, partial resection in 6 cases, subtotal resection in 4 cases and total resection in 4 cases. All patients underwent microsurgical third ventriculostomy. In 12 cases, stenting of stoma was performed in addition to ventriculostomy. Biopsy was informative in all cases. Postoperative follow-up period ranged from 3 to 44 months (mean 29 months). There was no postoperative hydrocephalus and need for shunting procedure. Burr hole microsurgery may be an alternative to endoscopic surgery for the treatment of pineal, periaqueductal and third ventricular tumors.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

BIOM-58. ZERO-WASTE MOLECULAR DIAGNOSTICS FROM BIOPSY NEEDLE WASHES

Abstract BACKGROUND Brain tumor classification has increasingly integrated molecular diagnostics into official criteria. However, biopsy tissue is limited due to the small quantity acquired in eloquent areas of the brain and is, therefore, usually earmarked for histology. We have identified that the fluid used to wash biopsy needles contains excess tumor material that can be diagnostically useful. Characterization of this non-zero-sum waste material provides an opportunity for improvement in the diagnosis and treatment for brain tumor patients. METHODS For suspected or established high grade brain tumor biopsies (n = 37 across a multi-institutional cohort at submission), neurosurgeons were instructed to save fluid used to wash biopsy needles. Samples were processed and characterized in a variety of methods to establish diagnostic utility including (1) cell-free DNA isolation and targeted panel sequencing (n = 13), (2) isothermal amplification of cell-free DNA from raw wash water for rapid diagnostics (n = 2), (3) cell-line generation (n = 24) and, (4) cell-free mutant protein capture and quantification (n = 9). RESULTS (1) 13 wash samples were considered for cf-tDNA extraction and Illumina TruSight Oncology 500 panel sequencing (with extracted DNA ranging from 20ng-40ug). In 2 returned cases (11 pending), concordance was 100% with clinical targeted panel sequencing where panels overlapped. (2) One case suspected of harboring H3K27M was subjected to targeted, loop-mediated isothermal amplification and Oxford Nanopore real-time sequencing, confirming an H3.3K27M diagnosis (11.8% allele fraction) within 1hr35min of receipt of sample from the operating room. (3) 5 cases resulted in primary cell culture generation (4) A novel single-molecule mutant protein quantification technique was performed on 9 cases. RESULTS from all analyses and concordance with outstanding sequencing will be presented. CONCLUSION We demonstrate that biopsy byproducts contain enough high-quality tumor-derived material to perform a variety of useful diagnostics with the potential to have immediate translational impact on standard of care.

INNV-24. MACHINE LEARNING-BASED SPECTROSCOPIC TISSUE DIFFERENTIATION IN FLUORESCENCE-GUIDED NEUROSURGERY

Abstract Maximal resection of malignant gliomas is hindered by difficulty in distinguishing tumor margins. Fluorescence-guided resection with 5-ALA assists in reaching this goal. Previously, we characterized five fluorophore emissions that accurately represent any spectrum measured from human brain tumor biopsies with a wide-field hyperspectral device. In this study, the effectiveness of these five spectra was explored for different tumor classification tasks in 891 hyperspectral widefield measurements of 184 patients harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8), which corresponds to up to 15000 spectra for a given test. The statistical differences in fluorophore abundances between classes were determined and visualized using dimensionality reduction techniques, including principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE). Three machine-learning models were trained to classify tumor type (12 classes), grade (3 classes), and glioma margins (3 classes). Five algorithms were tested with varying hyperparameters for each classification task. We explored whether PCA projection onto five different axes than fluorophore abundances can provide more information for visualization and classification. The abundances of the five a priori fluorophore spectra matched or outperformed the five optimal PCA components for all classification tasks. These five axes capture 96-99% of the variance in the dataset. Using random forests and multilayer perceptrons, the classifiers achieved average test accuracies of 74-82%, 79%, and 81%, respectively. All five fluorophore abundances varied between tumor margin type as well as between grades (p < 0.01). For tissue type, at least four of five fluorophore abundances were found to be significantly different (p < 0.01) between all classes. These results demonstrate the differing contribution of fluorophores in different tissue classes tissue, as well as the five fluorophores value as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery.

The Feasibility and Safety of Day Case Brain Tumour Biopsy: An Eight-Year Experience in the United Kingdom

The Feasibility and Safety of Day Case Brain Tumour Biopsy: An Eight-Year Experience in the United Kingdom

Adding Value to Liquid Biopsy for Brain Tumors: The Role of Imaging.

Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profiles alongside histopathology and imaging findings. While the World Health Organization (WHO) guideline recommends the genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, the acquisition of tumor tissue in the CNS is invasive and not always possible. Liquid biopsy is a non-invasive approach that provides the opportunity to capture the complex molecular heterogeneity of the whole tumor through the detection of circulating tumor biomarkers in body fluids, such as blood or cerebrospinal fluid (CSF). Despite all of the advantages, the low abundance of tumor-derived biomarkers, particularly in CNS tumors, as well as their short half-life has limited the application of liquid biopsy in clinical practice. Thus, it is crucial to identify the factors associated with the presence of these biomarkers and explore possible strategies that can increase the shedding of these tumoral components into biological fluids. In this review, we first describe the clinical applications of liquid biopsy in CNS tumors, including its roles in the early detection of recurrence and monitoring of treatment response. We then discuss the utilization of imaging in identifying the factors that affect the detection of circulating biomarkers as well as how image-guided interventions such as focused ultrasound can help enhance the presence of tumor biomarkers through blood-brain barrier (BBB) disruption.

TIPS-09 FIRST-IN-HUMAN PHASE 1 TRIAL OF THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY ANTI-TUMOR ACTIVITY OF WSD0922-FU (NCT04197934): TRIAL IN PROGRESS

Abstract WSD0922-Fu is an oral, central nervous system (CNS)-penetrant, small molecule, ATP non-competitive, reversible EGFR inhibitor which potently inhibits EGFR aberrations specific to non-small cell lung cancer (NSCLC) and high-grade astrocytoma (HGA). MC1914 (NCT04197934, sponsored by Wayshine Biopharma and FDA OOPD) is a first-in-human phase 1 dose-escalation trial investigating the safety and tolerability of WSD0922-Fu in patients with EGFR aberrant recurrent HGA and NSCLC. Adult patients with either recurrent EGFR mutant NSCLC with CNS metastases or recurrent EGFR mutant and/or EGFR amplified HGA were initially treated with oral WSD0922-FU, with doses escalated in cohorts based on a standard 3 + 3 design to determine the maximum tolerated dose (MTD). After establishing the MTD, this trial has now activated three dose expansion cohorts. Two of these cohorts evaluate different dose/schedule strategies in independent populations. The NSCLC cohort includes patients with EGFR mutant NSCLC and CNS metastases, and examines the safety, tolerability, plasma pharmacokinetics and preliminary efficacy of continuous WSD0922-Fu dosing (twice daily, seven days per week). The HGA cohort includes patients with EGFRvIII mutant HGA at first recurrence after prior radiation/temozolomide and examines the impact of higher doses of WSD0922-Fu administered intermittently (twice daily, five days per week). The HGA cohort also includes a food-effect study which evaluates the effect of the fed and fasted states on plasma PK. The third cohort (Brain tumor penetration cohort) includes patients with HGA (any EGFR mutation and/or EGFR amplification) who need a surgical resection for recurrent disease. Patients enrolled will be treated pre-operatively with WSD0922-Fu for five days, and tumor PK/PD will be examined in samples obtained from image-registered brain tumor biopsies. WSD0922-Fu therapy will be resumed after post-operative recovery. Patient enrollment to all three dose expansion cohorts is ongoing.

Social Determinants of Health and Associations With Outcomes in Pediatric Patients With Brain Tumors.

Social determinants of health (SDOH) are nonmedical factors that affect health outcomes. Limited investigation has been completed on the potential association of these factors to adverse outcomes in pediatric populations. In this study, the authors aimed to analyze the effects of SDOH disparities and their relationship with outcomes after brain tumor resection or biopsy in children. The authors retrospectively reviewed the records of their center's pediatric patients with brain tumor. Black race, public insurance, median household income, and distance to hospital were the investigated SDOH factors. Univariate analysis was completed between number of SDOH factors and patient demographics. Multivariate linear regression models were created to identify coassociated determinants and outcomes. A total of 272 patients were identified and included in the final analysis. Among these patients, 81 (29.8%) had no SDOH disparities, 103 (37.9%) had 1, 71 (26.1%) had 2, and 17 (6.2%) had 3. An increased number of SDOH disparities was associated with increased percentage of missed appointments ( P = .002) and emergency room visits ( P = .004). Univariate analysis demonstrated increased missed appointments ( P = .01), number of postoperative imaging ( P = .005), and number of emergency room visits ( P = .003). In multivariate analysis, decreased median household income was independently associated with increased length of hospital stay ( P = .02). The SDOH disparities are prevalent and impactful in this vulnerable population. This study demonstrates the need for a shift in research focus toward identifying the full extent of the impact of these factors on postoperative outcomes in pediatric patients with brain tumor.

Hemorrhagic complications during stereotactic biopsy of brain tumors

Relevance. Stereotactic biopsy (STB) is one of the main methods for diagnosing deep brain lesions. STB has several advantages over conventional intraoperative biopsy, as it is less traumatic and safer, especially for patients in critical condition. However, the most common complications of STB are hemorrhages, with a risk ranging from 0.9 % to 59.8 % depending on various studies. Intracranial hemorrhages are serious complications of surgical treatment of brain tumors, especially during biopsy using stereotactic techniques.Objective. To assess the risk of intracranial hemorrhages during STB of brain tumors and investigate possible factors influencing this risk, such as involvement of different brain regions in the neoplastic process, patient’s gender and age, degree of malignancy of the tumor, and use of different stereotactic devices.Materials and Methods. A retrospective study of data from 20 patients who underwent STB of brain tumors was conducted. Clinical data, examination results including coagulogram and aggregatogram, as well as data on involvement of different anatomical brain regions in the neoplastic process, degree of malignancy of the tumor, and use of a specific stereotactic device were analyzed.Results. Analysis of the frequency and structure of hemorrhagic complications of STB was performed, prognostic factors for high risk were identified, and preventive measures were proposed to reduce the number of hemorrhages.Conclusions. The introduction of the modern CRW Radionics stereotactic device into practice has reduced the frequency and severity of hemorrhagic complications after STB by two times. Lymphoproliferative processes and glioblastomas have a higher frequency of hemorrhages, but in most cases, they are clinically insignificant. There is a correlation between the degree of anaplasia of astrocytic tumors and the severity of hemorrhages. Ways to reduce the risks of intracranial hemorrhages during STB of brain tumors may include: careful preoperative planning of the biopsy trajectory; use of informative neurovisualization methods in planning the needle insertion trajectory; use of modern stereotactic systems by neurosurgeons who have undergone additional specialization and training on the specific device; use of modern biopsy needles. In addition, it is advisable to consider preoperative preventive hemostatic therapy in patients suspected of having a high degree of tumor anaplasia.