Central Tumors Research Articles

Are Imaging Evaluations of Soft-Tissue Masses Before Referral to a Specialized Center Being Performed Properly? A Systematic Review

Background/Objectives: Since the initial approach towards the clinical presentation of soft-tissue masses is challenging for frontline physicians, some countries use clinical practice guidelines. Proper imaging work-up is crucial to differentiate between soft-tissue tumors. Recently, ultrasonography and magnetic resonance imaging (MRI) have been widely used. But there is some controversy about whether pre-referral evaluations are being conducted properly. Thus, this study aims to assess whether the ultrasonography investigation of soft-tissue masses prior to referral to the musculoskeletal tumor center is being performed adequately in terms of indications, diagnostic accuracy, and referral interval, and to evaluate whether the pre-referral MRI for soft-tissue masses is being conducted reasonably concerning indications, imaging protocol, reporting, diagnostic accuracy, and cost-effectiveness. Methods: The study protocol was registered. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We performed a database search of the MEDLINE, Embase, and Cochrane Library. Then, two authors reviewed the studies, and the third author resolved any disagreement between them. A total of nine studies were included. The Risk Of Bias In Non-Randomized Studies-of Interventions was applied. Relevant data were extracted by two authors. Results: This review showed that the way that the imaging investigations are performed in non-specialized centers before referral was generally considered inappropriate. Conclusions: Frontline physicians should regard the alarm symptom as an indication for advanced imaging evaluation. Education and certification may be required for ultrasonography. MRI should be performed and interpreted in a specialized center or by a specialist with relevant expertise. Guidance may help reduce inappropriate imaging.

High detection rate of circulating-tumor DNA from cerebrospinal fluid of children with central nervous system germ cell tumors

Central nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies.

An Institutional Experience of Core Needle Biopsy with Cooperative Implementation by Pathologists and Head and Neck Oncologists in Salivary Gland Carcinoma.

A major problem in establishing treatment strategies for salivary gland carcinomas is the difficulty of preoperative histologic subtyping. Core needle biopsy (CNB) allows the collection of a small, intact specimens from the tumor center for detailed analysis. We evaluated the efficacy and limitations of preoperative diagnosis with CNB specimens collected using a newly developed 20-gauge needle designed to popularize its use. Paired preoperative CNB and surgical specimens from 41 patients with malignant salivary gland tumors were retrospectively reviewed. A histologic typing platform, including morphologic and immunohistochemical evaluation and fluorescence in situ hybridization, was evaluated using CNB specimens. Biopsy specimen quality, diagnostic accuracy, and immunohistochemistry concordance rates between biopsy and surgical specimens were analyzed. In 39 of the 41 patients, CNB provided high-quality specimens, enabling adequate morphologic, immunohistologic, and genomic analyses. In two patients, high-quality CNB specimens could not be obtained due to cystic fluid and tumor firmness. The overall accuracy of correct preoperative diagnosis was 75%. The success rate of histologic subtyping and HER2 immunostaining concordance between CNB and surgical specimens was lower in carcinoma ex-pleomorphic adenoma (CXPA) than in de novo carcinoma (histologic subtyping; CXPA vs de novo carcinoma 50% vs 89%, p = 0.016, HER2 concordance; salivary duct carcinoma [SDC] ex-PA vs de novo SDC 16% vs 100%, p = 4.66E-03). No recurrence occurred due to tumor seeding after CNB. Highly accurate histologic subtyping of salivary gland carcinomas can be performed by preoperative CNB; however, specificity can be more challenging in pathologically heterogenous tumors.

Tumor-derived extracellular vesicles disrupt the blood–brain barrier endothelium following high-frequency irreversible electroporation

High-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood–brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.3 cerebral endothelial cells were exposed to supernatants of H-FIRE or radiation (RT)-treated LL/2 and F98 cancer cells. Endothelial cell response was evaluated microscopically and via flow cytometry for apoptosis. sTDEV were isolated following H-FIRE and RT, characterized via nanoparticle tracking analysis (NTA) and transmission electron microscopy, and applied to a Transwell BBB endothelium model to quantify permeability changes. Supernatants of H-FIRE-treated tumor cells, but not supernatants of sham- or RT-treated cells, disrupted endothelial cell monolayer integrity while maintaining viability. sTDEV released by glioma cells treated with 3000 V/cm H-FIRE increased permeability of the BBB endothelium model compared to sTDEV released after lower H-FIRE doses and RT. NTA revealed significantly decreased sTDEV release after the 3000 V/cm H-FIRE dose. Our results demonstrate that sTDEV increase permeability of the BBB endothelium after H-FIRE ablation in vitro. sTDEV-mediated mechanisms of BBB disruption may be exploited for drug delivery to infiltrative margins following H-FIRE ablation.

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer.

Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes. This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group. Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin. RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Modern approach to bone comorbidity in prolactinoma.

Prolactinomas account for more than half of pituitary adenomas, and besides their clinical impact on fertility and gonadal function, they lead to detrimental effects on bone. Patients with prolactinoma are prone to deterioration of bone structure caused not only by prolactin (PRL) induced hypogonadism but also by its direct actions on bone cells and calcium metabolism. However, clinical studies have shown inconsistent evidence regarding whether PRL could have a deleterious effect independently from gonadal insufficiency on skeletal integrity. Seminal studies from our group reported an increased prevalence of vertebral fractures (VFs) in both female and male patients with prolactinoma. Treatment of prolactinoma with dopamine agonists can restore gonadal function and improve bone mineral density. Since the presence of VFs may be related to more aggressive disease, bone comorbidities in prolactinoma should be managed by a multidisciplinary team in line with the recent concept of 'pituitary tumors centers of excellence'. The review aims to evaluate the mechanism of PRL actions on bone, as well as to provide practical indications for a modern approach to the management of skeletal complications of patients with prolactin-secreting adenoma considering different clinical characteristics and outcomes.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

Abstract B026: Glioblastoma multiforme disseminates outside the central nervous system

Abstract Introduction: The liquid biopsy (LB) concept has gained significant attention in the last decade and has the potential to revolutionize cancer care. However, more validation in clinical trials is required on the value of LB in medical settings. Here, we focus on glioblastoma multiforme (GBM), a highly invasive and fatal subtype of the central nervous system malignant tumors. Circulating tumor cells (CTCs) are primary tumor cells released into the peripheral blood and migrating to distant organs. CTC presence is related to tumor spread and recurrence. In GBM, factors like short patient survival, the blood-brain barrier (BBB), and lack of lymphatic drainage in brain tissue make systemic dissemination rare but possible. Thus, noninvasive CTC detection can hold potential for diagnostic, predictive, and prognostic applications. Material and Methods: For cell stability preservation before sample processing, the peripheral blood samples from curatively resected GBM patients were collected preoperatively in Cell-Free DNA BCT® tubes (Streck, Inc.). CTCs were identified using CytoTrack CT11TM (2/C), a semi-automated immunofluorescence microscopy using glial fibrillary acidic protein, vimentin, and CD45 immunostaining, and DAPI counterstaining. The preliminary Kaplan-Maier survival analysis based on CTC positivity was performed in 39 patients with a follow-up longer than two years. Results: We analyzed the CTC presence in 100 GBM patient peripheral blood samples. The CTCs or cancer cell clusters were found in 35% of GBM patients. The Kaplan-Maier survival analysis did not show a correlation between CTC presence and survival. This phenomenon may be associated with the generally short survival of these patients, which is expected to increase with advances in oncology and palliative care and/or a possible suppression of tumor cell growth outside the CNS. Conclusions: We have observed the CTCs in the peripheral blood of GBM patients. The patient enrollment and clinical data recording are still ongoing. Citation Format: Pavel Stejskal, Josef Srovnal, Alona Rehulkova, Ondrej Kalita, Marek Slachta, Marian Hajduch. Glioblastoma multiforme disseminates outside the central nervous system [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B026.

CNSC-41. DABRAFENIB AND TRAMETINIB AS A PROMISING TREATMENT OPTION FOR PEDIATRIC POPULATION WITH LOW-GRADE GLIOMAS THAT HAVE BRAF V600E MUTATION:A BREAKTHROUGH IN THE FIELD OF NEURO- ONCOLOGY

Abstract Two-thirds of all pediatric malignant central nervous tumors, including high-grade (glioblastoma, anaplastic astrocytoma) and low-grade (ganglioglioma, pilocytic astrocytoma) carcinomas, are gliomas. Low-grade glioma(LGG) exhibits genetic alterations caused by the BRAF kinase mutation, such as replacing glutamic acid (E) in place of valine (V) at the 600 positions, known as the V600E point mutation. Pediatric low-grade gliomas (PLGGs) also comprise around one-third of juvenile brain tumors and are the most frequent central nervous system tumors. Patients were randomized 2:1 to dabrafenib plus trametinib (D+T) or carboplatin plus vincristine (C+V). Where possible, complete surgical removal is the mainstay of treatment for progressing or symptomatic PLGG.Radiation therapy has historically been used to treat PLGG in both up-front and salvage scenarios. To delay or avoid the necessity for radiation therapy in young children with advancing or incompletely resected PLGG, chemotherapy was created in 1980. On March 16, 2023, the Food and Drug Administration approved the use of trametinib (Mekinist, Novartis) with dabrafenib (Tafinlar, Novartis) in pediatric patients suffering from low-grade glioma (LGG) who require systemic therapy and are at least one year old. Nevertheless, early-stage clinical trials have produced encouraging results that may revolutionize the treatment of LGG in the near future.

QOL-07. LONG-TERM FOLLOW-UP OF PHYSICAL FUNCTION AND SOCIAL CONDITIONS IN CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND This paper presents an analysis of iving and social conditions from a long-term follow-up of Phase II clinical trial for central nervous system germ cell tumors conducted between 1995 and 2003. METHODS A retrospective analysis was performed on 228 cases, including 161 germinomas, 66 non-germinomas, and 1 mature teratoma, over a median follow-up of 222 months. There were 56 recurrences and 39 deaths recorded. The analysis at the final follow-up included final educational level, employment status, activities of daily living (ADLs), marital and parental status, and hormone replacement therapy. The study targeted 157 cases with more than 10 years of follow-up data. RESULTS At 20 years post-treatment, survival rates were 91% for germinomas and 65% for non-germinomas. At the last follow-up, ages ranged from 19 to 58 years (median 36 years). The Karnofsky Performance Status (KPS) was 80 or higher in 118 cases, 70 in 7 cases, and 60 or lower in 32 cases. Educational achievements were: elementary school in 1 case, middle school in 8, high school in 52, university in 45, and graduate school in 2. Employment status showed 37 unemployed, 4 in school, 23 part-time, 80 full-time, and 2 homemakers. Childbirth was reported in 16 men (18%) and 4 women (16%). The frequency of a KPS≧80 at the final follow-up was higher in initial germinoma cases than in non-germinoma cases (80 vs 62%, p=0.04), and was also higher in cases without recurrence (83 vs 47%, p<0.0001). Only the proportion of growth hormone supplementation showed a significant correlation with KPS (≧80: 19% vs <80: 3%, p=0.03). CONCLUSION Long-term social outcomes are favorable for germinoma patients without recurrence, while non-germinoma patients who have recurred and survived face tougher conditions, indicating significant treatment impacts. Managing treatment intensity and ensuring comprehensive long-term follow-up are crucial.

EPID-10. THE INCIDENCE OF PRIMARY BRAIN TUMORS IN JAPAN IN 2016-2019

Abstract The national cancer registries in Japan have started since 2016 and the actual number of cancer patients in including primary central nervous system (CNS) tumors in Japan was revealed. Average number of primary CNS tumors in 2016-2019 was 29,492 and the crude incidence rate per 100,000 people (CIR) was 23.30. Malignant and benign CNS tumors was 6,696 (22.7%) and 22,796 (77.3%) and each CIR was 5.29 and 18.00, respectively. Among 29,492 tumors, 10,537 (35.7%) meningioma, 5,217 (17.7%) pituitary adenoma, 4,537 (15.4%) neuroepithelial tumor, 2,730 (9.3%) neurinoma and 1,166 (4.0%) primary CNS lymphoma (PCNSL) were reported. Regarding to malignant brain tumors, 2,071 glioblastoma, 362 astrocytoma grade II, 390 anaplastic astrocytoma grade III, 138 pilocytic astrocytoma,182 oligodendroglioma grade II, 154 anaplastic oligodendroglioma grade III, 140 ependymal tumors, 128 embryonal tumors including 91 medulloblastoma, 211 germ cell tumor (GCT) were found. CIR of neuroepithelial tumor, glioblastoma, PCNSL, embryonal tumors and GCT were 3.64, 1.68, 0.93, 0.10 and 0.17, respectively. According to the Central Brain Tumor Registry of the United States (CBTRUS) (2016-2020), CIR in the US was 26.73, and age-adjusted incidence rates of primary CNS tumors per 100,000 population in the US based on the US population in 2000 (AIR) was 24.83 and AIR in Japan was 17.15. AIR of glioblastoma in the US and Japan was 3.27 and 1.05, AIR of PCNSL was 0.44 and 0.51, AIR of embryonal tumors was 0.21 and 0.16, AIR of GCTs was 0.08 and 0.27, and AIR of meningioma was 9.73 and 5.11, respectively. This report demonstrated that the incidence of neuroepithelial tumors and embryonal tumors in Japan was approximately half to one-third, whereas that of GCTs in Japan was approximately 3 times comparing to the US.

RADT-27. REPORT OF 9 CASES OF EMBRYONAL TUMORS OF THE CENTRAL NERVOUS SYSTEM WITH MULTILAYERED ROSETTES (ETMR)

Abstract OBJECTIVE Embryonal Tumors of the Central Nervous System with Multilayered Rosettes (ETMR) are rare, and there’s no standard treatment protocol. This article reports on the current treatment status and prognosis of ETMR in our hospital. METHODS We retrospectively collected patients with ETMR who received treatment in the Oncology Department of Guangdong sanjiu Brain Hospital from January 2017 to January 2021, analyzed their clinical data. RESULTS Among 31 cases of central nervous system embryonic tumors (excluding medulloblastoma and ATRT), 9 (29.03%) were ETMR. The median age at diagnosis was 3 years old (1-15), and the male to female ratio was 4:5. Among them, 5 cases were accompanied by C19MC gene variation. Tumor location:6 was in supratentorial, 1 in the pineal region, 1 in the pons, 1 in the cerebellopontine. Eight patients underwent surgical resection at the first diagnosis, with 6 cases of total resection, 1 case of partial resection, and 1 case of biopsy. One case was misdiagnosed as a germinoma in the pineal region at the initial. After recurrence, surgical resection was performed to confirm the pathology as ETMR. One case was misdiagnosed as glioblastoma during the first surgery. The initial treatment for 4 patients after surgery was radiotherapy combined with concurrent chemotherapy. Recurrence patterns: 2 cases were intracranial dissemination, 2 cases were local recurrence, 1 was spinal cord dissemination. One patient did not receive treatment after surgery and tumor recurrence 3 months later. Survival analysis: The median survival time was 20 months. The 1-year progression-free survival rate (PFS) and overall survival rate (OS) were 22% and 61%, and the 2-year overall survival rate (OS) was 31%. CONCLUSION ETMR has a low incidence and poor prognosis. It is easy to misdiagnose and NGS is necessary to assist diagnosis when needed. More effective treatment methods need to be explored.

CNSC-58. BIOPROCESSING OF VIABLE SURGICAL PEDIATRIC BRAIN TUMOR SPECIMENS FOR GENOME-GUIDED PERSONALIZED DRUG TESTING

Abstract Novel treatment approaches are urgently needed for pediatric central nervous system (CNS) tumors as they are the leading cause of cancer-related deaths in children. A lack of research materials impedes progress towards developing such therapies. Although various brain cancer biobanks exist, these rarely store viable patient-derived tissue and cells for live cell analyses, including cell fate assays and testing for drug sensitivities. We propose that a biorepository of viable cell dissociates and tissue broadly representing CNS tumor entities overcomes these limitations. From a combination of molecular diagnoses and histopathologic assessment of over 120 samples collected, we generated a biorepository of roughly 35 distinct entities of pediatric CNS tumors in our Stanford neuro-bioprocessing cohort. Based on the Central Brain Tumor Registry of the United States, the proportion of subtypes represented in our cohort match that of the general population with exceptions. We established a standardized bioprocessing pipeline that can be used as a template for tissue collection and model development in the broader disease context and for multiple downstream applications. Our emphasis on cryostorage of viable cells and tissue facilitates ad hoc live cell analyses. In addition to gaining a better understanding of tumor pathophysiology, we attempted a rapid bed-to-bench-to-bedside approach using comparative RNA expression profile analyses in an individual patient’s pilocytic astrocytoma. Novel drug targets were identified by analyzing RNA transcripts that are highly expressed (outliers) compared with a compendium of 12,747 brain and non-brain tumor samples. We validated outliers as drug targets using acute cell isolates, and identified a novel target in recurrent low-grade glioma. These studies illustrate that biobanking of viable patient-derived material enables developing personalized therapies with the goal of improving patient outcomes. As demonstrated here, patient-derived acute cell isolates facilitate identifying drug vulnerability, creating an opportunity for more personalized treatment of patients with CNS tumors.

EPID-05. THE INCREASED RISK OF MENINGIOMA AMONG INDIVIDUALS WHO ARE NON-HISPANIC BLACK IS MAGNIFIED AMONG MALES AND AMONG THOSE DIAGNOSED WITH GRADE 2-3 TUMORS

Abstract BACKGROUND Demographic factors associated with elevated meningioma incidence include older age, female sex, and Black race. There are limited data exploring how meningioma risk in Black persons varies across the lifespan, interacts with sex, and differs by tumor grade. METHODS The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry combining data from the CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, covering the entire U.S. population. Meningioma diagnoses from CBTRUS (2004-2019) were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) as compared to non-Hispanic White individuals (NHW) across 10-year age intervals, and stratified by sex and WHO tumor grade (grade 1 versus grades 2/3, combined). RESULTS From 2004-2019, a total of 53,890 NHB individuals and 322,373 NHW individuals were diagnosed with a primary meningioma. The NHB to NHW IRR was elevated, beginning in the third decade of life (IRR=1.19; 95%CI: 1.11-1.28), peaking in the seventh decade (IRR=1.29; 95%CI: 1.26-1.31), and persisting throughout the lifespan. The IRR peaked in the seventh decade of life across strata of tumor grade, but, within this age group, NHB race/ethnicity was associated with substantially higher risk of grade 2/3 tumors (IRR=1.59; 95%CI: 1.48-1.70) than grade 1 tumors (IRR=1.27; 95%CI: 1.24-1.29). Meningioma risk was elevated in NHB females compared to NHW females (IRR=1.16; 95%CI: 1.15-1.18) and among NHB males compared to NHW males (IRR=1.22; 95%CI: 1.19-1.25), revealing synergistic interaction between NHB race/ethnicity and male sex (PInteraction=0.001). CONCLUSIONS This study identifies an elevated risk of meningioma in NHB relative to NHW, beginning shortly after puberty and continuing across the lifespan. NHB race/ethnicity conferred higher risk of meningioma among men than among women, and higher risk of developing WHO grade 2/3 than grade 1 tumors. These results highlight meningioma as a major potential source of racial disparities in neuro-oncology.

NIMG-05. ARTIFICIAL INTELLIGENCE-BASED RESPONSE ASSESSMENT FOR PATIENTS RECEIVING LASER INTERSTITIAL THERMAL THERAPY

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a minimally invasive option for tissue diagnosis, cytoreduction, and rapid post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. As ablated tissue remains in situ, post-LITT edema may be associated with apparent increased lesion size and transient clinical worsening, complicating assessment of progression. METHODS All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments. RESULTS Across 384 unique MRI exams, 61LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and returned to baseline thereafter. Based on established criteria, volumetric disease progression was defined as lesion expansion 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients experiencing volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015). CONCLUSIONS We observed a stereotyped increase in CeLV at 1 – 3 months post-LITT, which resolved within 6 months of the procedure. Post-LITT disease response can be reliably and feasibly assessed with criteria that account for this transient CeLV expansion. Automated lesion segmentation may speed adoption of volumetric response assessment criteria to clinical practice.

QLTI-13. A REVIEW OF THE BEST TREATMENT STRATEGY FOR NEUROFIBROMATOSIS TYPE 2 PATIENTS THROUGH A SINGLE-CENTER RETROSPECTIVE STUDY: HOW TO ORCHESTRATE MULTIMODAL TREATMENT OPTIONS

Abstract PURPOSE Neurofibromatosis type 2(NF2) is an autosomal-dominant tumor predisposition syndrome that affects the whole neuro-axis and causes various neurological symptoms decreasing the quality of life throughout the patient’s lifespan. However, due to the diversity of related diseases and the complexity of treatment, there are many cases in which only partial treatments are performed, the timing of the treatment is missed, and inappropriate treatment modality selection is made despite the intervention of many clinicians. Therefore, to increase the overall understanding of the disease, the single-institution experience was analyzed. MATERIALS AND METHODS Between 1998 and 2022, a total of 80 patients who clinically suspected NF2 visited our Brain Tumor Center. After excluding the patients with follow-up loss, the remaining 48 patients were finally analyzed. The patient’s symptoms, diagnosis process, treatment process, and outcomes were analyzed. RESULTS The average age at the time of symptom onset was 31.0(2-63) year-old. Hearing impairment was the major primary symptom(46.8%) among the patients. Five patients(10.9%) had family history of NF2. Thirty-five patients(76.1%) was clinically diagnosed as a NF2 for the bilateral vestibular schwannomas, and 34 patients(73.9%) had intracranial meningiomas, and 37 patients(80.4%) had spinal lesions at the time of diagnosis. Eleven patients were genetically confirmed as NF2. For vestibular schwannomas, 16 patients had surgical resection and 20 patients took gamma-knife surgery as a primary or secondary treatment. For intracranial meningiomas, 16 patients had surgical resection, 13 patients took gamma-knife surgery, and 15 patients took conventional radiation therapy as a primary or secondary treatment. Ventriculo-peritoneal shunt due to increased intracranial pressure was performed in 4 patients(8.7%). For spinal lesions, 16 patients had surgical resection. CONCLUSION NF2 is a disease group requiring a multidisciplinary team approach. The key to treatment is to set and implement a treatment sequence and method tailored to each patient. For this, an overall understanding of the disease and the treatment options is essential.

CNSC-54. CENTRAL AND BOUNDARY-DRIVEN GROWTH PATTERNS DOMINATE RESPECTIVELY IDH WILD-TYPE AND MUTANT GLIOMAS

Abstract Diffuse gliomas are the most prevalent primary malignant brain tumors in adults and are characterized by invasive growth and poor prognosis. Tumor cells infiltrate the brain parenchyma and spread to distant sites. The aim of this study is to characterize the spatial heterogeneity, mode, and direction of tumor development to identify key areas for localized treatment. Neuronavigation was employed to collect n=134 image-guided samples from n=16 adult patients with diffuse gliomas, including n=7 IDH wild-type (IDHwt) and n=9 IDH mutant (IDHmut) tumors from regions with and without MRI abnormalities. Collected samples were subjected to targeted and shallow whole-genome sequencing. Somatic variants were used to determine the evolutionary processes governing heterogeneity. Examination of the dN/dS ratio, Tajima’s D score, and MOBSTER model suggested that all tumors are consistent with neutral evolution, as previously reported. Considering that genetic heterogeneity was a result of stochastic mutations, we used phylogeographic relationships between samples to dissect the spatiotemporal development of these tumors. Evolutionary (patristic) and cartesian (Euclidean) distances between sample pairs from the same patient were correlated in n=2/9 IDHmut and n=2/7 IDHwt patients, suggesting that migratory or punctuated evolutionary processes play a major role in tumor diffusion. An examination of spatial diffusion revealed that the latest descendant appeared peripherally in n=5/9 IDHmut patients, suggesting boundary-driven growth. In the remaining cases, three patients exhibited centrally-driven growth, whereas a fourth patient displayed a mixed pattern. In contrast, in n=4/7 IDHwt patients, descendants appeared closer to the tumor center, suggesting centrally-driven growth. In the remaining three IDHwt patients, one patient showed a diffusion that was consistent with boundary-driven growth, while the other two patients showed a mixed pattern. Taken together our data suggest that IDHwt tumors tend to develop centrally, whereas IDHmut tumors preferably develop outward. Our data could aid in tailoring localized treatment based on projected growth patterns.

QOL-04. THE UNDER-UTILIZATION OF PALLIATIVE CARE SERVICES BY PATIENTS WITH GLIOBLASTOMA HIGHLIGHTS THE IMPORTANCE OF DISCUSSIONS AROUND PALLIATIVE CARE: A CROSS-SECTIONAL STUDY WITH CARE PARTNERS OF PATIENTS WITH GBM RECRUITED FROM FACEBOOK SUPPORT GROUPS

Abstract Glioblastoma (GBM) is a terminal brain cancer that has a rapid onset and results in symptoms such as headaches, vomiting, seizures, anxiety, depression, agitation, speech impairment, memory impairment, infections, brain bleeds, mobility changes, changes in sleep patterns, and cognitive changes. Palliative care helps patients diagnosed with an incurable or chronic disease manage physical, social, and psychological symptoms and has been shown to increase survival for patients with cancer. Previous data of former care partners of patients with GBM indicated only 30% of patients used palliative care whereas 90% used hospice. To better understand the reasons for underutilization of palliative care patients with GBM, 38-question survey about the use of palliative care, type of medical center where treatment occurred, and discussions with care team members about palliative care was given to current care partners recruited from Facebook support groups in February 2024. Inclusion criteria: current primary care partner of a patient with GBM, over the age of 18, and willing to participate (IRB exempt; H24-0393). The care partner was excluded if their patient was no longer living. Of the 77 current care partners, 56 reported they did not use palliative care as part of their care team. The use of palliative care was similar among care facilities (community hospital, major medical center, university hospital, brain tumor center). When care team members discussed palliative care with patients and their care partners (n=21), 71% of the dyads used palliative care. When care team members did not discuss palliative care (n=56), the use of palliative care was much lower at 7%. Interestingly, 55% of respondents reported they would benefit from knowing more about ways to increase physical and emotional support. This data suggests discussions around palliative care increase the use of palliative care services among patients with GBM and their care partners.

DDDR-23. DECODING GLIOBLASTOMA DRUG RESISTANCE DYNAMICS USING NOVEL MICROFLUIDIC EX VIVO MODELS

Abstract Glioblastoma (GBM) is clinically challenging due to its aggressive nature and limited treatment options. Current standard of care involves surgical resection and chemoradiation with temozolomide (TMZ). GBM, however, often returns post-treatment fueled by its complex biology and the presence of resilient GBM stem cells. Compounding the issue is the blood-brain barrier, which poses a formidable obstacle to drug delivery into the brain. Understanding the molecular dynamics post-therapy within the brain, influenced by the tissue microenvironment, is key for developing more effective therapeutic strategies. Unfortunately, existing research models have fallen short in capturing the complexity of GBM and its response to treatment. While animal models have been a mainstay in GBM research, their ability to predict human responses has been called into question, highlighted by the disappointing results seen in clinical trials. We are therefore advancing bioprinting-based approaches for modeling various components of the tumor microenvironment to gain insight into mechanisms of drug resistance. We report on the development of three novel microfluidic platforms to investigate and interrogate GBM biology. First, we have developed a novel microfluidic model of GBM, termed GlioFlow-3D, produced through a combination of 3D printing methods. GlioFlow-3D mimics specific aspects of the perivascular niche, including protection from circulating TMZ. Second, we have adapted GlioFlow-3D as part of a platform to investigate advanced ultrasound techniques for delivering novel therapeutics into the human brain. Third, we are developing a novel approach aimed at exploring the relationship between the brain extracellular matrix and tumoral cells using bioprinting of living tumor organoids obtained from patients with a history of recurrence. By integrating bioprinting technologies with patient-derived models to create novel ex vivo platforms, we aim to obtain new insights into the intricate dynamics of drug resistance in GBM, ultimately paving the way for more effective therapeutic strategies. Funding: The Brain Tumor Center Research Award (UCGNI) The ARC Project - CCHMC and UC joint Research Award

BIOM-30. NOVEL HISTOLOGIC AND MOLECULAR BIOMARKERS FOR OLIGODENDROGLIOMA

Abstract Oligodendrogliomas are progressive, infiltrative gliomas. While new molecular criteria were introduced in 2016 for diagnosing oligodendroglioma, the grading criteria remains largely unchanged. We evaluated histologic and molecular features for new biomarkers of aggressive behavior, using a cohort of 184 specimens diagnosed as low grade oligodendroglioma within the Duke Brain Tumor Center Biorepository. To identify tumors meeting current molecular criteria for oligodendroglioma, IDH1/2 status was confirmed by whole exome sequencing and 1p/19q codeletion confirmed using inferred copy number variation. First, we assessed for a histologic feature called hypercellular nodules (HCN), which are foci of increased cellularity in regions of otherwise lower cellularity tumor. In patients with newly diagnosed grade 2 oligodendroglioma, 16% (15/92) had HCN. While the median overall survival (OS) was 24.1 years without HCN, the median OS with HCN was only 13.6 years (p<0.02, Mantel-Cox test). We then assessed for homozygous deletion of CDKN2A. Cases with potential CDKN2A homozygous deletion by inferred copy number variation were validated by fluorescence in situ hybridization. In patients with newly diagnosed grade 2 oligodendroglioma, 2% had homozygous CDKN2A deletion (2/107). While the median OS with intact or hemizygous CDKN2A loss was 21 years, it decreased to 3.8 years with homozygous CDKN2A deletion (p<0.0001, Mantel-Cox test), although interpretation is limited given the rarity of homozygous CDKN2A loss at initial diagnosis. For recurrent grade 2 oligodendroglioma, 6% had homozygous deletion (5/77). While the median OS with intact or hemizygous CDKN2A loss in recurrent oligodendroglioma was 25.4 years, it decreased to 6.7 years with homozygous CDKN2A deletion (p< 0.04, Mantel-Cox test). These studies provide support for using HCN and CDKN2A homozygous deletion as grading criteria for oligodendroglioma. Further studies are ongoing, including covariate analysis, expanded cohorts, and ongoing analysis of whole exome sequencing data to identify additional genetic alterations correlated with overall survival.