Anaplastic Astrocytoma Research Articles

NIMG-22. QUANTITATIVE BRIGHTNESS ANALYSIS OF 5-ALA FLUORESCENCE IN GLIOMA SURGERY

Abstract OBJECTIVE The 5 aminolevulinic acid (5-ALA) is used for intraoperative tumor visualization in neurosurgery. We hypothesized that glioma may vary in pathology according to the brightness of 5-ALA fluorescence, which we quantified and compared with the pathological results of glioma. METHODS From 2019 to 2023, we investigated 28 glioma patients who underwent surgery with 5-ALA. The pathological diagnosis was based on classification of WHO 2016. The 5-ALA was administered before surgery, and the brightness of 5-ALA fluorescence was quantified. RESULTS Seventeen cases of glioblastoma (GBM), four cases of anaplastic astrocytoma (AA), three cases of oligodendroglioma (OL), and four cases of low grade glioma (LGG) were examined. The mean (SD) brightness of 5-ALA fluorescence was 155.9 (56.0) in GBM, 180.5 (64.7) in AA, and 66.3 (18.8) in OL. The brightness in OL was significantly lower than that in GBM and AA (Scheffe’s test, p<0.05). All LGGs showed negative in the brightness. CONCLUSIONS The brightness of 5-ALA fluorescence was shown to vary by pathology, which may contribute to intraoperative diagnostic support.

ANGI-07. A CASE OF HYPERBARIC OXYGEN USED AS A TREATMENT MODALITY FOR ANAPLASTIC ASTROCYTOMA

Abstract Although its precise mechanism is unclear, hyperbaric oxygen is thought to impede the growth of tumor cells by inhibiting tumor hypoxia, a known driver for angiogenesis. We present a case of a 32-year-old pilot who developed sudden onset aphasia and disorientation which led to hospitalization and imaging. He was diagnosed with anaplastic astrocytoma and underwent resection, radiation, and chemotherapy with temozolomide. Approximately one year later, MRI showed enlarging non-enhancing T2/FLAIR hyperintense mass in the right temporal lobe. He received 4 cycles of lomustine. Four months later, MRI showed slight increase in the size of ring enhancement around the treatment area. These findings were thought to be related to treatment-related changes. After 4 doses of bevacizumab every 2 weeks, there was improvement in surrounding vasogenic edema. However, after 7 doses, his MRI brain demonstrated increase in treatment-related changes with more vasogenic edema. He also had worsening left-sided weakness, unable to lift his left arm against gravity, dysarthria, and cognitive slowing. MRI perfusion supported treatment-related changes rather than tumor growth. He then started hyperbaric oxygen treatments and after 20 sessions of treatment, his vasogenic edema and his left-sided weakness improved. After 60 sessions of hyperbaric oxygen, he noticed further improvement in his strength and short-term memory. Four months after completion of his hyperbaric oxygen, he was found to have increasing size of ring-enhancing lesion and was restarted on hyperbaric oxygen treatments in addition to bevacizumab and low-dose temozolomide. He completed a total of 100 rounds of hyperbaric treatments. MRI showed improvement and stability. His left-sided weakness continued to improve. Hyperbaric oxygen alone or combined with other treatment modalities may be a promising therapy to improve quality of life. Further research will assist with mechanisms through which hyperbaric oxygen works and patient outcomes.

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.

PATH-46. DETECTION OF CDKN2A/B HOMOZYGOUS DELETION BY DNA METHYLATION AND DNA NEXT GENERATION SEQUENCING: A COMPARISON

Abstract CDKN2A/B homozygous deletion status is critical for grading of several central nervous system (CNS) tumors, including IDH mutant astrocytoma, pleomorphic xanthoastrocytoma, and meningioma. CDKN2A/B status can be assed using variety of methods, but the accuracy varies due to technical and analytical variables. Here we sought to compare sensitivity of CDKN2A/B homozygous deletion detection by NGS and DNA methylation array derived copy number analysis. We retrospectively analyzed 100 CNS tumors diagnosed at NYU Langone Health between 2020 and 2023. All tumors were profiled by whole genome DNA methylation profiling using the Illumina EPIC array. Copy numbers were analyzed using the ‘conumee’ R package and visual inspection. Next-generation sequencing (NGS) analysis was performed by NYU Langone Genome PACT, a 510(k) FDA cleared (K202304) matched tumor-normal 607 gene panel. Variant allele frequency of canonical driver mutations was used to molecularly estimate tumor cell content. Discrepant cases were assed using targeted qPCR. Our cohort of 100 CNS tumors included glioblastoma (N=75), IDH mutant astrocytoma (N=14), oligodendroglioma (N=4), pleomorphic xanthoastrocytoma (N=2), meningioma (N=1), infantile hemispheric glioma (N=1), central neurocytoma (N=1), diffuse midline glioma K27-altered (N=1), and anaplastic pilocytic astrocytoma (N=1). By DNA methylation, CDKN2A/B homozygous deletion was detected in 54 cases, hemizygous deletion was detected in 13 cases, and no deletion was detected in 33 cases. By NGS, CDKN2A/B homozygous deletion was detected in 31 cases, hemizygous deletion was detected in 28, and no deletion was detected in 41 cases. DNA methylation detected a homozygous deletion in 23 cases that were not detected by NGS. All cases of homozygous deletion detected by NGS were also detected by DNA methylation. DNA methylation derived copy number assessment is more sensitive for CDKN2A/B homozygous deletion than next generation sequencing.

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.

The engagement of Ras/Raf/MEK/ERK and PLCγ1/PKC pathways regulated by TrkB receptor in resistance of glioma cells to elimination upon apoptosis induction

The most aggressive tumors of human central nervous system are anaplastic astrocytoma (AA, III grade) and glioblastoma multiforme (GBM, IV grade) with an extremely bad prognosis. Their malignant character and resistance to standard therapy are correlated to the over-expression of survival pathways such as Ras/Raf/MEK/ERK and PLCγ1/PKC regulated by TrkB receptor. Therefore, the aim of this study was to investigate the engagement of those pathways in human glioma cells resistance for apoptosis induction by Temozolomide treatment. Two cancer MOGGCCM (AA) and T98G (GBM) and normal human astrocytes (NHA) cell lines were utilized. The tested inhibitors single and simultaneous action with Temozolomide affection on apoptosis induction was analyzed by MTT, microscopic observations and flow cytometry. Bcl-2:beclin-1 complexes occurrence was also assessed. siRNAs were used for direct proof of tested pathways engagement in gliomas resistance to apoptosis elimination. The most effective in eliminating gliomas with minimal astrocyte damage was 5 μM PLCγ1 inhibitor (U-73122) for MOGGCCM and 15 μM for T98G cells, and 1 μM LOXO-101 for all cancer cells. Sorafenib, Temozolomide, U-73122, and LOXO-101 effectively eliminate cancer cells. Single applications of sorafenib and Temozolomide were effective, but had lower efficiency than U-73122 and LOXO-101. These drugs induced apoptosis, affecting mitochondrial membrane potential and caspases 3, 8, and 9 activity. The study found that a Bcl-2:beclin-1 complex formation was observed when apoptosis was dominant. Inhibiting the pathways regulated by TrkB receptor combined with Temozolomide action, led to successful gliomas elimination. Those results might serve as basis for modern targeted treatment development.

Utility and Safety of 5-ALA Guided Surgery in Pediatric Brain Tumors: A Systematic Review.

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed.

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database

Abstract Background Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims at evaluating the prognostic impact of molecular typing of pediatric spinal cord ependymomas. Methods Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database between 1992 and 2022 were included. Forty-seven tumors were analyzed by DNA methylation array profiling. In six cases, HOXB13 and MYCN proteins were detected as surrogate markers for specific methylation classes. Ten patients had NF2-related schwannomatosis. Results With a median follow-up time of 4.9 years (y), 5y- and 10y-overall survival (OS) were 100% and 86%, while 5y- and 10y-progression-free survival (PFS) were 65% and 54%. Myxopapillary ependymoma (SP-MPE, n=32, 63%) was the most common molecular type followed by spinal ependymoma (SP-EPN, n=17, 33%) and MYCN-amplified ependymoma (n=2, 4%). One case could not be molecularly classified, and one was reclassified as anaplastic pilocytic astrocytoma. 5y-PFS did not significantly differ between SP-MPE and SP-EPN (65% versus 78%, p=0.64). MYCN-amplification was associated with early relapses (<2.3y) in both cases and death in one patient. Patients with SP-MPE subtype B (n=9) showed a non-significant trend for better 5y-PFS compared to subtype A (n=18; 86% versus 56%, p=0.15). The extent of resection and WHO tumor grades significantly influenced PFS in a uni- and multivariate analysis. Conclusions Molecular typing of pediatric spinal ependymomas aids to identify very-high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making.

Epidemiology and survival of primary intracranial malignant tumor patients with drop metastasis: a population-based analysis.

Drop metastasis significantly impacts the survival of patients with primary intracranial malignant tumors. Using the information of collaborative stage from the SEER database, we aim to analyze the epidemiology and prognosis of primary intracranial malignant tumor patients with drop metastasis. We analyzed the distribution of patients and the frequency according to the demography and clinical characteristics of patients with drop metastasis. We also analyzed the survival of these patients with drop metastasis. Multivariate Cox proportional hazards models were used to analyze possible prognostic indicators. A total of 56,839 cases with primary intracranial malignant tumors were ultimately included in this cohort study. A total of 792 cases were confirmed to have drop metastasis. The average rate of drop metastasis was 1.4%. Most of the patients with drop metastases were diagnosed before ten years old. The three most common primary intracranial malignant tumors with drop metastasis were glioblastoma, embryonal/primitive/medulloblastoma, and anaplastic astrocytoma. Embryonal/primitive/medulloblastoma had the highest drop metastasis rate, at 11.6%. Tumors located in the infratentorial space and ventricles had a higher rate of drop metastasis than tumors in other locations. The prognosis for patients with drop metastasis is poor. Routine complete treatment (surgery of the primary tumor plus chemoradiotherapy) can significantly improve overall survival. We conducted a population-based analysis of primary intracranial malignant tumor patients with drop metastasis. Our study can help clinicians acquire general information on the epidemiology and survival of primary intracranial malignant tumor patients with drop metastasis.

PDOC-12 PEDIATRIC BRAIN TUMOR INCIDENCE, AND TREATMENT MODALITY AT KILIMANJARO CHRISTIAN MEDICAL CENTER

Abstract INTRODUCTION Pediatric brain tumors (PBT) a significant health concern, they are the primary cause of cancer-related deaths among children. PBTs in Low- and Middle-Income Countries are diagnosed late due to insufficient resources. This abstract describes Pediatric Brain tumor incidence and treatment modalities at Kilimanjaro Christian Medical Center (KCMC) Cancer Care Center (CCC), Moshi, Tanzania from December 2016 to March 2024. METHOD Data on pediatric patients treated at the CCC between Dec. 2016 and March 2024, were analyzed. Inclusion criteria were a primary brain tumor and patients aged 0-19 at the time of diagnosis. All patients were previously diagnosed by computer tomography/ magnetic resonance imaging. Variables retrospectively collected from patient’s medical records were: demographic characteristics (age, gender, Place of residence, and insurance status), previous history of malignant diseases, incidence date, and treatment modality. RESULTS Total of 748 cases of pedeatric cancer were diagnosed at CCC. Of all the pediatric cancers diagnosed, brain cancer accounted for 22(2.9%). Out of these cases of brain cancer, 63.6% were males and 36.4% were females.Majority of them came within the Kilimanjaro region. 41% were palliated while 59% had a curative intent at the time of diagnosis, 22.7% died between December 2016 to March 2024.Embryonal tumors were (40.9%) with a breakdown that includes 6 Medulloblastoma and 3 cases of Craniopharyngioma (teratoid/rhabdoid), gliomas (36.4%) with sub-types such as Ependymoma, Anaplastic Astrocytoma, Pilocytic Astrocytoma, Pineocytoma, Stem glioma, and Tectal glioma, unspecified cases (13.6%), and Pineoblastoma were (9.1%). Surgery was used in 40.9% of cases, radiotherapy in 31.8%, and chemotherapy in 72.7%. Chemoradiotherapy was used in 31.8% of cases. 13.6% of cases utilized a combined approach, including chemotherapy, radiotherapy, and surgery. CONCLUSION PBT incidence at KCMC is 2.9%, improving access to screening, accurate diagnosis and treatment modalities are essential in identifying and managing PBT in our setting.

Proapoptotic and antimigration properties of osthole in combination with LY294002 against human glioma cells.

Anaplastic astrocytoma and glioblastoma multiforme are infiltrating and vascularized gliomas with a high degree of chemoresistance and metastasis. Our previous studies have shown that osthole may be of great importance in the treatment of gliomas. Therefore, in this work, for the first time, coumarin was used in combination with LY294002-an inhibitor of the PI3K-Akt/PKB-mTOR pathway, which is overly active in gliomas. MOGGCCM and T98G cells were incubated with osthole and LY294002, alone and in combination. Staining with specific fluorochromes was used to visualize cell death and the scratch test to assess the migration. The level of proteins was estimated by immunoblotting. Forming protrusions were visualized by SEM, and immunocytochemistry was used to determine the localization of proteins. Additionally, the expression of Bcl-2, beclin 1 and Raf kinase was silenced using specific siRNA. The obtained results showed that osthole in combination with LY294092 effectively inhibited the migration of glioma cells by reducing the level of metaloproteinases and Rho family proteins, as well as decreasing the level of N-cadherin. In addition, the combination of compounds induced apoptosis. New combination of compounds shows a high pro-apoptotic potential and also inhibits the migration of gliomas cells.

Intraoperative Comparison Between Strain Elastography and Preoperative Magnetic Resonance Imaging Features in High-Grade Gliomas Using Fusion Imaging: A Pilot Study

To compare the elastographic patterns of high-grade gliomas (HGGs) solid portions and those of adjacent healthy brain parenchyma, on intraoperative ultrasound, with magnetic resonance image (MRI) characteristics. Clinical records and images of HGGs patients, operated between June and December 2018, were retrospectively reviewed. Fusion images were used to compare preoperative gadolinium-enhanced T1-weighted MRI/fluid-attenuated inversion recovery images (Gd-T1 MRI/FLAIR) to intraoperative strain elastography (SE). FLAIR/Gd-T1 MRI images were used to define: enhancement patterns (absent/whole lesion/peripheral) and lesions' characteristics (primary and secondary pattern, further subdivided in solid/necrotic/cystic/infiltrating). HGGs SE patterns were categorized as homogeneous/inhomogeneous, while lesions' primary and secondary patterns as stiff/intermediate/elastic. The SE motive of neighboring healthy brain parenchyma was defined similarly. 18 patients (M:F, 11:7; mean age: 53 years) harboring 14 glioblastomas (77.8%, GBMs) and 4 anaplastic astrocytomas (22.2%, AAs) were compared. GBMs typically enhanced peripherally and had a primary necrotic pattern (78.6% and 64.3%, respectively), while AAs did not enhance and were solid (75% both) at T1-Gd MRI and FLAIR images. At SE AAs had a homogeneous stiff primary pattern, whereas the majority of GBMs primary patterns were heterogeneous (85.7%) and intermediate (78.6%). Three major SE patterns defined HGGs and adjacent healthy brain parenchyma. SE patterns varied accordingly to HGG histotypes and Gd-T1 MRI/FLAIR characteristics.

Immunotherapy for children with malignant brain tumors

The incidence of high-grade malignant gliomas (MG) ranges from 35 to 46% of all central nervous system tumors. Despite combined therapy including surgery, radiation treatment and chemotherapy, overall five-year survival does not exceed 10%. The advent of novel immunotherapeutic strategies has promoted a renewed hopes for the treatment of MG. The aim of the present study was to improve the survival rates of glioma patients. Our study included 5 pediatric patients at the median age of 7.6 years (2-16). Three pts had anaplastic astrocytoma (AA) (1st relapse, 1 pt; 2nd relapse, in 2 pts), One patient was diagnosed with glioblastoma multiforme (GBM) (3rd recurrence), and 1 child had diffuse brainstem glioma (BSG). The median time to the first relapse was 12 months (4 to 16), the second relapse occurred at a median of 5 months (1 to 8). The protocol of immunotherapy included combined administration of autologous dendritic cell-based vaccine (DV) and repeated intrathecal/intraventricular injections of donor allogeneic immunocompetent cells (alloIC) for at least 2 years. Two of 3 pts with AA experienced a progression-free interval of 67 and 71 months. One patient with 3rd GBM relapse is alive without any treatment for 13.3 years after starting the immunotherapy. The median time of follow-up was 67 months, with the 2-year overall survival rate of 58%. Two pts died from the disease progression within 6 and 7 months from the beginning of immunotherapy. Over the period of treatment, the patients received a median of 20 alloIC injections (8 to 60), and 18 DV administrations (8 to 44). No serious side-effects were observed. Immunotherapy could be an promising option for treating patients with high-grade malignant gliomas refractory to conventional therapy and, therefore, deserves further investigations.

AB048. Evidence of effectiveness of neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas.

Recurrent high-grade glioma (HGG) is a challenge with limited treatment options and a poor prognosis. We conducted an open-label phase II study: neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas (NCT04588987), and interim analysis showed very promising results. We are further searching for evidence of the effectiveness of this strategy. Patients with recurrent HGG received neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), and 14 days later received surgery for recurrent tumor resection. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200 mg) and 4 weeks after surgery with the daily apatinib (250 mg) until investigator assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS). When patients suspected progress during per-protocol treatment, re-surgery for resection of lesion was done, and the tissue was further examined. Between October 9, 2020, and March 30, 2024, 24 patients were enrolled [19 glioblastomas, one World Health Organization (WHO) grade 4 diffuse astrocytoma, three anaplastic astrocytoma, and one anaplastic oligodendroglioma]. Nineteen patients with interim analysis data, and showed the median progression-free survival (PFS) was 4.8 months [95% confidence interval (CI): 4.4-5.2], the median OS was 12.9 months (95% CI: 9.3-16.4) respectively, with a median follow-up time of 17.5 months (95% CI: 9.0-26.1). There were two patients who suspected progress and received second surgery. One patient showed real tumor progression with active tumor cells. While another patient the histology revealed mainly necrosis with inflammatory cells. Five patients initially showed increased enhancement on magnetic resonance imaging (MRI) but without increased symptoms, and showed continuous improvement when receiving further treatment. This immuno-target combination neoadjuvant therapy in recurrent HGG demonstrated encouraging efficacy and revealed some evidence of efficacy, and worth to further investigate.

Presentation, surgical outcome, and supplementary motor area syndrome risk of posterior superior frontal gyrus tumors.

Following resection of posterior superior frontal gyrus (PSFG) tumors, patients can experience supplementary motor area (SMA) syndrome consisting of contralateral hemiapraxia and/or speech apraxia. Given the heterogeneity of PSFG tumors, the authors sought to determine the risk of postoperative deficits and assess predictors of outcomes for all intraparenchymal PSFG tumors undergoing surgery (biopsy or resection), regardless of histology. This was a retrospective single-center cohort study of adult PSFG-region tumors undergoing biopsy or resection by a single surgeon. A total of 106 consecutive patients undergoing 123 procedures (21 biopsies, 102 resections) fulfilled inclusion and exclusion criteria. Anaplastic astrocytomas were the most frequent among resected tumors (39% vs 29%), while glioblastomas were most common among biopsies (38% vs 27%) (p < 0.0001). The biopsy cohort was more likely to have tumor involvement outside the PSFG (90% vs 62%) (p = 0.011), most commonly in the motor cortex (67% vs 31%) (p = 0.005). Seizures were the most common presenting symptom in the resection cohort (p = 0.017), while motor deficits were more common in the biopsy cohort (58% vs 29%) (p < 0.001). Immediate postoperative neurological deficits occurred in 71 cases (58%), but only 3 of the deficits were permanent at 6 months of follow-up (2%). Postoperative SMA syndrome occurred in 48 cases (47%) and was significantly associated with involvement of the motor cortex (p = 0.018) or cingulate gyrus (p = 0.023), which were also significant in multivariate analysis as risk factors for SMA syndrome. However, postoperative SMA syndrome was not significantly associated with overall survival (p = 0.51). There were no perioperative deaths, but corpus callosum involvement (p < 0.001), contrast enhancement (p = 0.003), and glioblastoma pathology (p = 0.038) predicted worse overall survival in patients undergoing resection. Nearly half of all patients undergoing resection of PSFG-region tumors experience a postoperative SMA syndrome. Individuals with corpus callosum and/or motor cortex involvement may be at an increased risk of experiencing SMA syndrome. However, these deficits are usually transient, and the risk of permanent new deficits is very low (3%). Preoperative characteristics including corpus callosum involvement and tumor enhancement-in addition to pathology-might serve as predictors of overall survival within this patient population.

AB025. Efficacy of 5-ALA brightness analysis for malignant brain tumor surgery.

For fluorescence-guided neurosurgery, 5-aminolevulinic acid (5-ALA) is widely used for intraoperative tumor visualization. We quantified the brightness of 5-ALA by Image J and report the pathological results of glioma, and non-tumor lesions. From 2019 to 2023, we investigated 27 high-grade glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM) and four cases of anaplastic astrocytoma (AA) were examined. The pathological diagnosis was based on the classification of World Health Organization (WHO) 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness was quantified. Other than high-grade glioma, four low-grade gliomas (LGGs), two radiation necrosis, and one inflammation patients were evaluated by Image J. In GBM, the mean brightness was 134.5±65.4, except for one negative case. AA showed the mean brightness with 180.5±51.6. All LGGs showed negative in the brightness. In two radiation necrosis cases, the mean brightness was 139.5±37.4. In one inflammatory case, the brightness was 239, but after the lesion removed, the adjacent brain parenchyma showed bright, and the border was not clear. In one GBM case, the ventricle was opened, and the brightness difference between the tumor and the ventricular wall was observed. 5-ALA brightness analysis by Image J would be helpful to distinguish between malignant glioma and LGG, and other non-tumor lesions to support rapid pathological diagnosis. Also, it would be useful to distinguish between the tumor and the ventricle wall. As for radiation necrosis and inflammation, border of the lesion is unclear.

AB055. Infantile high-grade glioma (IHG)-a case series of Hong Kong experience.

Infantile high-grade glioma (IHG) is diagnosed in patients less than 12 months of age. Studies have shown that it displays a more stable genome and is usually single mutation-driven. The most identifiable mutations are receptor tyrosine kinase (RTK) fusion, such as neurotrophic tyrosine receptor kinase (NTRK) family, reactive oxygen species (ROS1), anaplastic lymphoma kinase (ALK), and mesenchymal-epithelial transition (MET) factor. The current principal treatment remains to be surgery, but it is challenging for a complete resection due to hemispheric involvement. Use of chemotherapeutic drugs for IHG is still under debate, with targeted therapy showing efficacy in promoting tumor shrinkage. Despite being a challenging central nervous system (CNS) tumor, the overall survival of IHG is superior to other high-grade gliomas. This is a retrospective review of local IHG patients and their outcome. Up till the end of 2022, we identified eight IHG patients in our local data. Mean age of diagnosis was 3 months. There were four males and four females. Seven patients had histological diagnosis of glioblastoma and one patient had a diagnosis of anaplastic astrocytoma. One patient had her tumor located in the infratentorial region. Four patients had multilobar involvement. NTRK fusion was found in four patients (ETV6-NTRK3 fusion and TPR-NTRK1 fusion). ALK fusion was found in one patient (HMBOX1-ALK). ROS1 fusion was found in one patient (ZCCHZ8-ROS1). All patients underwent chemotherapy, with four patients switched to NTRK inhibitors and one patient to ROS1 inhibitors afterward. Surgery was performed at various time points for these patients. Two patients passed away, at 22 and 35 months of age at submission of this abstract. Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.

Multiscale segmentation net for segregating heterogeneous brain tumors: Gliomas on multimodal MR images

In this research, the 3D volumetric segmentation of heterogeneous brain tumors such as Gliomas- anaplastic astrocytoma, and Glioblastoma Multiforme (GBM) is performed to extract enhancing tumor (ET), whole tumor (WT), and tumor core (TC) regions using T1, T2, and FLAIR images. Therefore, a deep learning-based encoder-decoder architecture named “MS-SegNet” using 3D multi-scale convolutional layers is proposed. The proposed architecture employs multi-scale feature extraction (MS-FE) block the filter size 3 × 3 × 3 to extract confined information like tumor boundary and edges of necrotic part. The filter of size 5 × 5 × 5 focuses on varied features like shape, size, and location of tumor region with edema. The local and global features from different MR modalities are extracted for segmenting thin and meshed boundaries of heterogeneous tumors between anatomical sub-regions like peritumoral edema, enhancing tumor, and necrotic tumor core. The learning parameters on introducing the MS-FE block are reduced to 10 million, which is much less than other architectures like 3D-Unet which takes into consideration 27 million features leading to the consumption of less computational power. A customized loss function is also prophesied based on a combination of dice loss and focal loss along with metrics such as accuracy and Intersection over Union (IoU) i.e. the overlapping of ground truth mask and predicted value for addressing the class imbalance problem. For evaluating the efficacy of the proposed method, four evaluation metrics such as Dice Coefficient (DSC), Sensitivity, Specificity, and Hausdorff95 distance (H95) are employed for analyzing the model's overall performance. It is observed that the proposed MS-SegNet architecture achieved the DSC of 0.81, 0.91, and 0.83 on BraTS 2020; 0.86, 0.92, and 0.84 on BraTS 2021 for ET, WT, and TC respectively. The developed model is also tested on a real-time dataset collected from the Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh. The DSC of 0.79, 0.76, and 0.68 for ET, WT, and TC respectively on the real-time dataset. These findings show that deep learning models with enhanced feature extraction capabilities can be readily trained to attain high accuracy in segmenting heterogeneous brain tumors and hold promising results. In the future, other tumor datasets will be explored for the detection and treatment planning of brain tumors to check the effectiveness of the model in real-world healthcare environments.

A Four-Grade Astrocytoma Classification System with Optimal Feature Selection Using Ant Colony Optimization Algorithm

An efficient Four-Grade Astrocytoma brain tumor classification is proposed in this research work. The work highlights the optimal feature selection using a hybrid combination of Ant Colony Optimization (ACO) algorithm and machine learning techniques, leading to better classification accuracy. A diverse set of features including spatial and frequency domain features will provide better discrimination of patterns. ACO provides a robust and efficient mechanism for exploring the vast space of possible feature subsets. A total of 135 features are extracted including Tamura features, Gabor Wavelet Features, Coiflet Wavelet Coefficients, Speeded Up Robust Features, and GLCM features. Ant Colony Optimization is used to find out the optimum set of features. The selected feature set is used for training a Decision Tree classifier, where the Astrocytoma MRI images are categorized into four grades of astrocyoma namely, pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma and glioblastoma multiforne. Classification is also performed using KNN classifier, SVM classifier and Ensemble Bagged Tree Classifier. Performance metrics like accuracy, sensitivity, specificity, precision and FScore are utilized to evaluate the proposed system’s performance. It is found out that the decision tree classifier outperforms the other classifiers. Thus this integrated approach of ACO with machine learning classifiers results in improved Astrocytoma classification performance aiding clinicians in making accurate treatment decisions.

Re-irradiation in High-grade Glioma: An Experience from A Series of Five Patients

ABSTRACT The management of recurrences or residual lesions following radiation therapy for brain tumors poses a challenging clinical scenario, necessitating careful consideration for treatment strategies. There is no standard of care for patients with recurrent high-grade glioma. Treatment strategies include resection, re-irradiation, systemic agents, and intratumoral thermotherapy using magnetic iron-oxide nanoparticles (nanotherapy). A small percentage of patients can undergo repeat surgery and re-radiation is also a matter of concern due to anticipated toxicities. However, advancements in radiation technology have made people more willing to consider re-irradiation. In this study, we retrospectively analyzed patients who underwent re-irradiation for high-grade glioma. In total, five patients were included in the study. All five patients had anaplastic astrocytoma. All patients were considered for surgery, followed by radiation therapy during the initial treatment. Three patients had an average of 4 years of symptom-free survival, while the other two had symptoms ranging from moderate to severe. Three of the five patients died within 1 year of taking the re-radiation; however, two patients are still in follow-up.