Treatment Of High-grade Gliomas Research Articles

Real-world experience with TTFields in glioma patients with emphasis on therapy usage.

Tumor Treating Fields (TTFields) has emerged as a significant adjunctive component in the treatment of high-grade gliomas following the EF-14 trial in 2017. The incorporation of TTFields, alongside cyclic temozolomide therapy, has demonstrated improved patient outcomes when the usage exceeds 18 h per day (75% usage). Post-hoc analysis of the EF-14 trial has demonstrated that therapy usage exceeding 90% is associated with an additional benefit, while rates above 50% have also proven effective in literature. Given the cost-intensive nature and mild- to- moderate constraints associated with the therapy, our objective is to generate real-world data on therapy usage through a retrospective analysis at a high-throughput academic center. Between June 2015 and February 2022, a total of 113 high-grade glioma patients received TTFields therapy. Eight patients discontinued TTFields therapy within 2 months with less than 50% usage and were excluded from further analysis. For the remaining patients, the median age was 51 years (range: 20-76 years) and the mean preoperative Karnofsky index was 80%-90%. Most of the patients (75.2%) initiated therapy concurrently with first-line treatment, of whom 27.6% started TTFields therapy concomitant to the first cycle of temozolomide. 15.2% started TTFields therapy in the second-line and 9.5% in the third-line setting. The study cohort had an average therapy duration of 9.3 months with 3.2 break days per month. The mean therapy usage was 65.5% (SD 17.6%). Usage was highest during the first 3 months, with rates of 77.7%, 72.3%, and 71.6%, and then dropped to around 60% in the following 6 months. Linear regression found no predictors of usage, such as age, timing of therapy initiation, and duration or gender. 55% of patients continued TTFields beyond the first recurrence. Interestingly, no drop in usage rates was observed before tumor recurrence was communicated. However, after diagnosis, patients exhibited a significant drop in usage to an average of 52.3%. This high-volume, real-world TTFields usage data reveal that the extent of usage falls short of the intended 75%. It highlights the importance of monitoring and promoting adherence to maximize its potential benefits in managing high-grade glioma patients. Furthermore, strategies to expedite therapy initiation and improve long-term adherence are warranted.

Surgery in recurrent brain glioma, does it improve clinical outcome?

IntroductionGliomas account for 24% of all primary brain and CNS tumors. Histologically, gliomas were categorized into subtypes and grades (I through IV). Low-grade gliomas are grade I and grade II, while high-grade gliomas are grade III and grade IV. The gold standard for treatment of high-grade glioma is the most extensive safe surgical resection followed by radiotherapy combined with chemotherapy. However, recurrence of glioma is inevitable. Management of recurrent cases is still controversy.Aim of the workThe purpose of this research was to examine the efficacy of reoperation for cases of recurrent glioma in improving patients’ outcome.MethodsThis study included 25 patients with recurrent glioma admitted and operated upon in neurosurgical department in Assiut University hospitals through 1 year from 1/11/2020 to 30/10/2021.ResultsThere were 17 male (68%) and 8 female (32%), their age incidence ranged from 25 to 74 years with a mean age of 49.09, gross total resection of recurrent cases could be done in 14 (56%) patients, subtotal resection in 6 (24%) and partial in 5 (20%), all of recurrence were found at the same site almost the same of primary tumor except that two cases were radionecrosis and one patient revealed aggressive transformation from anaplastic astrocytoma to GBM by the end of the study period, and 17 (68%) patients alive and 8 (32%) died.ConclusionSurgical management of recurrent gliomas in selected patients is generally associated with improved functional performance and prolonged survival. Patients’ Karnofsky score at recurrence is an important prognostic factor for both low-grade glioma and high-grade glioma.

Postoperative concurrent chemoradiotherapy plus apatinib for patients with high-grade glioma: a retrospective cohort study.

Radiotherapy plus temozolomide followed by adjuvant temozolomide was the standard treatment for high-grade gliomas. This study aimed to explore the effectiveness and safety of the addition of apatinib in patients with high-grade gliomas after surgery. In this retrospective cohort study, patients with high-grade glioma [World Health Organization (WHO) grade III or IV] treated with apatinib and concurrent chemoradiotherapy (cCRT) after surgery from October 2017 to February 2021 were reviewed. High-grade glioma patients used cCRT alone in the same period were reviewed as the control group. Progression-free survival (PFS), overall survival (OS), the grade of peritumoral brain edema (PTBE) and safety profiles were recorded. Cox regression analyses were used to determine the associated factors of PFS and OS. A total of 60 patients with high-grade glioma were reviewed, with 30 patients in the apatinib plus cCRT group and 30 patients in the cCRT group. The median PFS of the apatinib plus cCRT group compared with the cCRT group was 8.53 vs. 7.33 months (P=0.62), and the median OS was 13.70 vs. 14.30 months (P=0.93). Multivariate analysis revealed that only pathological grade was independently associated with PFS [hazard ratio (HR) =4.445, 95% confidence interval (CI): 1.857 to 10.641, P<0.001] and OS (HR =3.737, 95% CI: 1.530 to 9.123, P=0.004). The apatinib plus cCRT also improved PTBE (P=0.001), and decrease the corticosteroids use than cCRT alone (P=0.002). No grade 3 or higher adverse event was observed in both groups. Post-operative cCRT plus apatinib was feasible for patients with high-grade glioma, with manageable toxicities.

Innovations in intraoperative therapies in neurosurgical oncology: a narrative review.

High-grade gliomas (HGG) represent the most aggressive primary brain tumors in adults, characterized by high recurrence rates due to incomplete resection. This review explores the effectiveness of emerging intraoperative therapies that may extend survival by targeting residual tumor cells. The main research question addressed is: What recent intraoperative techniques show promise for complementing surgical resection in HGG treatment? A comprehensive literature review was conducted, examining recent studies on intraoperative therapeutic modalities that support surgical resection of HGG. Techniques reviewed include laser interstitial thermal therapy (LITT), intraoperative brachytherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), and focused ultrasound (FUS). Each modality was evaluated based on clinical application, evidence of effectiveness, and potential for integration into standard HGG treatment protocols. Findings indicate that these therapies offer distinct mechanisms to target residual tumor cells: LITT provides localized thermal ablation; intraoperative brachytherapy delivers sustained radiation; PDT and SDT activate cytotoxic agents in tumor cells; and FUS enables precise energy delivery. Each method has shown varying levels of clinical success, with PDT and LITT currently more widely implemented, while SDT and FUS are promising but under investigation. Intraoperative therapies hold potential to improve surgical outcomes for HGG by reducing residual tumor burden. While further clinical studies are needed to optimize these techniques, early evidence supports their potential to enhance the effectiveness of surgical resection and improve patient survival in HGG management.

NCOG-37. SINGLE CENTER EXPERIENCE OF IDH INHIBITORS IN THE TREATMENT OF RECURRENT HIGH GRADE GLIOMAS

Abstract BACKGROUND The antitumor effect of IDH inhibitors in high grade gliomas (HGG) is not well known, with conflicting views regarding the role of IDH status and the potential for resistance to DNA damage treatments. We present the outcomes of patients with HGG that were treated with IDH inhibitors at our institution. METHODS We performed a retrospective review of patients with IDH mutant gliomas treated with FDA approved IDH inhibitors (ivosidenib and enasidenib) in the past 5 years at our institution. One cycle of IDH inhibitor was defined as treatment for 28 days. RESULTS We identified 10 HGG patients (both oligodendrogliomas and astrocytomas). Median age at diagnosis was 31 years and 7 were male. Seven patients were diagnosed as WHO grade 3. Six patients were WHO grade 3 oligodendrogliomas, three WHO grade 4 astrocytomas, and one patient WHO grade 3 astrocytoma. Only one patient received enasidenib and the rest were treated with ivosidenib. Eight patients were started on IDH inhibitors after 3 recurrences. Median number of cycles was 5. One patient received 23 cycles, and one patient received 11 cycles. All patients underwent resection, 4 received chemotherapy (including temozolomide, bevacizumab, and CCNU), and 4 radiation prior to starting IDH inhibitors. One patient was treated with Tumor Treating Fields. Five patients progressed during the study follow up, and 3 patients died. Four patients are still on treatment. No serious adverse events. Median PFS after starting an IDH inhibitor was 6 months. DISCUSSION IDH inhibitors were well tolerated in IDH mutant HGG patients previously treated with DNA-damaging agents. It may have a role in the treatment of HGG with multiple recurrences with 3 patients showing stable disease for more than 18 months. More studies are needed to clarify the role of IDH inhibitors in patients with IDH mutant HGG.

SURG-51. DECOMPRESSIVE HEMICRANIECTOMY IN HIGH-GRADE GLIOMA PATIENTS: CLINICAL AND RADIOGRAPHIC OUTCOMES

Abstract BACKGROUND Decompressive hemicraniectomy (DHC) is an uncommonly needed treatment in high-grade gliomas (HGG), most used for refractory increased intracranial pressure (ICP) from vasogenic edema, mass effect, or related complications. Outcomes and imaging following DHC are not well described. METHODS We retrospectively identified cases of DHC for HGG at our institution since 2019. RESULTS Three patients with HGG underwent DHC (2 females, ages 39-70) for newly diagnosed (2 patients) or recurrent tumor (1 patient). Causes of increased ICP were tumor/vasogenic edema (2 patients) or abscess (1 patient). Subsequent cranioplasty was performed in 2 patients: at 1.8 months after DHC in one patient, and at 8.6 months in another patient who developed sinking skin flap syndrome (SSFS). SSFS presented as progressive worsening of tumor-related neurologic deficits after completion of radiation therapy with no change in imaging, followed by frank signs of increased ICP 8 months after DHC. Two patients died of disease progression (5.3 months and 9.1 months after DHC), and one patient remains alive at 13.5 months (patient with SSFS; neurologic deficits virtually resolved after cranioplasty repair). Imaging will be described for all patients. CONCLUSION DHC can be a life-saving intervention in HGG. When feasible, early cranioplasty should be considered to avoid complications, including SSFS, which may present with neurological deficits without corresponding imaging change.

SURG-58. COLD ATMOSPHERIC PLASMA (CAP) CAUSES SELECTIVE TUMOR CELL DEATH VIA APOPTOSIS AND FERROPTOSIS IN MALIGNANT GLIOMA CELLS

Abstract BACKGROUND High-grade gliomas (HGGs) are primary brain tumors associated with significant morbidity and mortality, and despite advances in neuro-oncology, the prognosis remains poor. Cold atmospheric plasma, a novel experimental anti-cancer therapeutic tool, is a near-room temperature ionized gas generated at atmospheric pressure. It has many promising results in vitro and in vivo with a variety of cancers. CAP cytotoxicity appears to be selective to cancer cells without significant damage to surrounding healthy tissues. We aim to evaluate the efficacy of CAP in generating tumor-selective cytotoxicity against high-grade glioma. METHODS B16, U87, GL261, patient derived high grade glioma, human neural stem cells (LM-NSC008) and astrocytes (NHA hTERT) were treated with CAP. Proliferation and propidium iodide (PI)/annexin V flow cytometry assays were employed to quantify cytotoxicity, cell cycle phases and apoptosis. Cells were pre-treated with ferroptosis inhibitors Ferrostatin-1 and Deferoxamine (DFO) in rescue assays. Cerebral organoids were transplanted with fluorescent tumor cell lines and stained with cleaved caspase-3, ki67 and transferrin receptor. RESULTS CAP induces dose dependent cell death in all glioma cell lines tested. CAP induces an accumulation of intracellular ROS, most prominent in glioma cells. CAP-mediated cell death involves apoptosis and ferroptosis. CAP selectively leads to apoptosis in tumor implanted organoids and leads to decreased proliferation in malignant and non-malignant cells. CAP leads to a shift into G0 phase of all treated cells, malignant and non-malignant. CONCLUSIONS CAP treatment induces dose-dependent increases in ROS and apoptosis in HGG lines tested more significantly than in NHAs and hNSCs. CAP induces decreased proliferation and G0 phase cell cycle arrest in all CAP-treated cells. CAP-mediated cytotoxicity was significantly mitigated with DFO pre-treatment in HGG cells, suggesting that ferroptosis plays a critical role in the mechanism of CAP treatment in HGG. CAP led to selective glioma cell death in tumor implanted cerebral organoids.

EXTH-20. EXPLORING EUPHOL’S THERAPEUTIC EFFECT IN ADULT AND PEDIATRIC BRAZILIAN HIGH-GRADE GLIOMAS PRE-CLINICAL MODELS

Abstract High grade gliomas (HGG) are among the most aggressive brain tumors affecting both adults and children. Adult HGG (aHGG) account for almost 25% of all brain tumors in adults, with glioblastoma (GBM) being the predominant subtype. Pediatric HGG (pHGG), though less common, accounts for 3-15% of primary brain tumors in children and exhibits distinct genetic profiles compared to aHGG. Standard treatment for HGG in both adults and pediatric patients includes maximal surgical resection followed by temozolomide (TMZ)-based chemotherapy and radiation therapy. Our group previously reported that euphol, a natural compound derived from the sap of Euphorbiaceae family plants, exerts cytotoxicity effects on glioma cells. In this study, we investigated the therapeutic potential of euphol in primary cell cultures and xenograft models derived from six Brazilian HGG patients, including three adults and three pediatrics. In vitro, euphol exposure significantly reduced cell viability reduction, clonogenic capacity, and migration, while enhancing apoptosis in all six primary cultures. Additionally, euphol sensitized glioma cells to TMZ, resulting in a synergistic cytotoxic effect. In vivo, euphol reduced tumor growth in both GBM and pHGG models, and prolonged the survival of mice in the GBM orthotopic experiment. These findings highlight the promising therapeutic potential of euphol for treating high-grade gliomas in both adult and pediatric populations.

TMOD-04. SAFETY AND EFFICACY DATA FROM A CLINICAL TRIAL OF SONODYNAMIC THERAPY WITH 5-ALA HCL ORAL SOLUTION AND CV-01 DELIVERED WHOLE HEMISPHERIC LOW-INTENSITY NON-ABLATIVE ULTRASOUND IN PET FRENCH BULLDOGS WITHDE NOVO NATURALLY OCCURRING HIGH-GRADE GLIOMA

Abstract To date, no animal model has been able to accurately test emerging therapeutics for high-grade glioma. Pet dogs’ high-grade gliomas closely mimic human tumors histopathologically and radiologically as well as with poor clinical survival. Dogs with these tumors have notably shorter survival than humans, with French Bulldogs showing the shortest survival of all breeds affected, aiding swift therapeutic evaluations. We report the first use of the novel CV-01 device delivering non-ablative low-intensity diffuse ultrasound (LIDU) with oral 5-ALA as a recurrent high-grade glioma treatment in a veterinary safety and efficacy trial. This Phase 1 study focused on safety, with secondary outcomes assessing histopathological efficacy markers (CC3, Iba1) and overall survival. After one SDT treatment pre-resection, treatments every 3-4 weeks were administered to eight French Bulldogs, totaling 60 administrations (average of 7.5 total treatments/patient). The control group matched breed, age, and histopathologic diagnosis. Average age was 6.35 years (range: 4.8 – 7.8 years), slightly older than controls (5.9 years, range: 3.0 - 9.9 years). No complications or toxicities were noted, and MRI scans showed no damage to the normal brain. Histopathologic analysis from four canine tumor samples revealed increased apoptosis and immune activation markers post-SDT (e.g. cleaved caspase 3 [CC3] and ionized calcium-binding adaptor molecule 1 [Iba1]), indicating selective tumor cell death. Median overall survival in the treatment group reached 205.5 days (6.8 months) compared to 55 days (1.8 months) in controls, with the longest survival at 587 days (versus 213 in controls). Although preliminary, these results affirm the safety of 5-ALA-mediated SDT in canine glioma patients. A multi-center, First-In-Human trial in recurrent high-grade glioma recently completed enrollment, aiming to further validate canine trials for emerging high-grade glioma therapeutics.

Clinical results of helical tomotherapy for high-grade gliomas

Introduction Radiotherapy-related damage of normal tissue inevitably influences the treatment outcomes in the context of high-grade gliomas (HGGs) treatment. We reported the survival outcomes and toxicities of patients with HGG treated with helical tomotherapy (HT) and the prognostic factors were analyzed. Materials and methods A total of 67 patients (29 had grade III and 38 had grade IV HGGs) who received HT between January 2016 and June 2020 were analyzed. Overall survival (OS) and progression-free survival (PFS) from the beginning of HT and OS from surgery were assessed, and toxicity and disease control were described briefly. Results For patients with grade III HGGs, median OS (mOS) and median PFS (mPFS) from the beginning of HT were 68.933 and 62.967 months, respectively. For patients with grade IV HGGs, mOS and mPFS from the beginning of HT were 19.667 and 7.23 months, respectively. No grade ≥3 acute or late nonhematologic toxicities were observed. Multivariable Cox regression analysis showed that methylguanine methyltransferase (MGMT) methylated status, age, number of lesions, WHO grade, and monocyte count for PFS were significant. Age, monocyte count, and isocitrate dehydrogenase (IDH) status for OS. Conclusion Treatment of HGGs with HT appears to be potentially effective and safe. HT is promising for glioblastomas (GBM), especially complex cases with infratentorial involvement or multiple lesions. This study highlighted the potential clinical significance of systemic inflammation indicators in predicting survival and disease progression.

Exploring therapeutic potentials of Tridax procumbens for Glioma: An in-silico approach employed network pharmacology, molecular docking, and molecular dynamics simulation

Glioma is a frequent type of malignant brain tumor, originating from glial cells. Despite advances in understanding the molecular biology and genetics of gliomas, the treatment of high-grade gliomas remains challenging. This study focuses on the identification of potentially active compounds from the medicinal plant Tridax procumbens for the treatment of glioma. Using computational approaches such as virtual screening, ADMET profiling, network pharmacology, molecular docking, and molecular dynamics, ten potential phytocompounds were identified from a total of 106 compounds. Further analysis revealed a network of 170 common genes between the phytochemicals and disease genes, comprising 161 nodes and 2083 edges. Molecular docking experiments demonstrated that luteolin, quercetin, and 6-Hydroxyluteolin 6,3′-dimethyl ether 5-rhamnoside exhibited potential inhibitory activities against two targeted proteins, HSP90 and SRC. Luteolin with HSP90 protein and Quercetin with SRC protein complexes were found to be the highest in docking performance with the least binding affinities −10 kcal mol−1 and −9.3 kcal mol−1 respectively. Molecular dynamics simulations explored Quercetin-SRC and Luteolin-HSP90 interactions over 300 nanoseconds. Quercetin-SRC binding showed dynamic and flexible behavior with an RMSD, RMSF, and radius of gyration of 0.22 nm, 0.35 nm, and 2.12 nm, respectively, whereas Luteolin-HSP90 binding was more stable and less flexible, with an RMSD of 0.14 nm, RMSF of 0.14 nm, a radius of gyration of 1.74 nm, and maintained consistent strong interactions with specific solvent accessibility. The analysis of free binding energy in Quercetin-SRC and Luteolin-HSP90 complexes indicated highly favorable formation driven by altered interactions, with delta total values of −33.74 and −29.26 kcal/mol, respectively. Both phytochemical luteolin and quercetin showed strong inhibitory potential against HSP90 and SRC proteins, indicating their potential as effective therapeutic agent for glioma treatment. This integrated approach emphasizes the significance of these compounds in advancing treatment strategies for glioma. However, pre-clinical and clinical experimentations are required to establish the potential of T. procumbens as a treatment for glioma.

CAR T-cell therapy for gliomas.

To review the landscape of chimeric antigen receptor T-cell (CAR T) therapy for gliomas as seen in recently published trials and discuss on-going challenges with new cancer immunotherapy treatments. Given how CAR T therapy has revolutionized the treatment of several hematologic malignancies, there has been increasing interest in using immunotherapy, and particularly CAR T therapy for gliomas. Within the past decade, several first in human trials have published early patient experiences showing treatment is generally well tolerated but with limited efficacy, which may be improving with newer evolutions in CAR T design to overcome known resistance mechanisms in glioma treatment. CAR T therapy is a promising avenue of treatment for high-grade gliomas, which have a universally poor prognosis as well as limited therapeutics. There are a growing number of CAR T clinical trials for CNS tumors and thus, an understanding of their treatment strategies, toxicity management, and overcoming resistance mechanisms will be important for both clinical practice and to identify areas for future research.

Advancements and challenges: immunotherapy therapy in high-grade glioma- a meta-analysis of randomized clinical trials.

High-grade gliomas (HGG)are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells. This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG. Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events. We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05months, with virotherapy at 11.79months and notably longer for DCV at 24.11months. The mean progression-free survival (PFS) for ICIs was 3.65months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvementwith a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile. Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.

Tumor-related epilepsy in high-grade glioma: a large series survival analysis.

Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes. Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status. Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset. Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required.

Differentiation of Edematous, Tumoral and Normal Areas of Brain Using Diffusion Tensor and Diffusion Kurtosis Imaging

Glioma is the most common type of intracranial tumor, and surgery followed by radiation therapy is the best treatment for high-grade glioma. Presurigical planning for glioma tumor resection and radiotherapy treatment require proper delineation of tumoral and peritumoral areas of brain.

HGG-43. DIFFUSE PEDIATRIC HIGH GRADE GLIOMA SUCCESSFULLY TREATED WITH MULTIMODAL THERAPY

Abstract BACKGROUND Pediatric high grade glioma (HGG) have a dismal prognosis despite aggressive treatment. In this report, we discuss a patient with HGG successfully treated with combination of resection, radiotherapy, chemotherapy, and biologic therapy. RESULTS An 8-year-old male presented with intermittent headaches, vomiting and fatigue. Imaging demonstrated four solid/cystic enhancing intra-axial lesions within the left cerebral hemisphere- two within the left frontotemporal region, one in the superior parietal region, and one in the temporal lobe, all with perilesional edema and resultant subfalcine herniation with midline shift. The patient underwent subtotal resection of the frontotemporal and parietal lesions. Histopathology was consistent with glioblastoma. Whole exome sequencing revealed alterations in TP53, ATRX, PTEN, TSC2 as well as subclonal mutation in NF1. The tumor was unable to be further classified by DNA methylation. However histopathologic and molecular findings support the diagnosis of diffuse pediatric-high grade glioma, H3-wildtype and IDH-wildtype. The patient received adjuvant 59.4 Gy focal proton therapy with concurrent temozolomide and maintenance chemotherapy with temozolomide and lomustine for 6 cycles. End of therapy imaging demonstrated complete resolution of all sites of disease. Due to high likelihood of recurrence, the patient was subsequently started on targeted therapy with everolimus and ribociclib which continue to be well tolerated without dose adjustments. The patient remains stable and without recurrence 2.5 years since diagnosis, and 15 months since initiation of biologic therapy. Additionally, the patient underwent testing for cancer predisposition which revealed presence of TP53 heterozygous mutation consistent with Li-Fraumeni syndrome. The patient remains without other malignancies on surveillance imaging per LFS guidelines. CONCLUSION Our case report illustrates the value of both chemotherapy and biologic therapy in treatment of HGG. In addition to this, it emphasizes the importance of germline testing for cancer predisposition in patients with high grade tumors.

Single center experience of IDH inhibitors in high-grade gliomas.

e14036 Background: IDH inhibitors have shown to improve progression free survival in low grade gliomas. Antitumor effect in high-grade gliomas is not well known, with conflicting views regarding the role of IDH mutations in high-grade gliomas and the potential for resistance to DNA-damage-inducing therapies. We present the outcomes of high-grade gliomas that were treated in our institution with IDH inhibitors. Methods: We performed a retrospective review of patients with gliomas treated with FDA approved IDH inhibitors (ivosidenib and enasidenib) in the past 5 years at our institution (January 1st 2019- January 1st 2024). Our search identified 32 patients of which 11 were identified as high-grade gliomas (both oligodendrogliomas and astrocytomas). Institutional Review Board PA17-0222 was used for this study. Results: Eleven high grade, IDH-mutant glioma patients treated with IDH inhibitors were identified with a median age at diagnosis of 31 years; 63.6% of these patients were men. Over 63% of patients were categorized as WHO grade 3 and 36.4% as grade 4 tumors. Over 63% of patients were astrocytoma (4 out of 7 patients with WHO grade 4 astrocytoma) while the rest were oligodendrogliomas. All patients underwent initial resection and had received radiation plus at least one prior line of systemic therapy prior to starting an IDH inhibitor. Over 72% were started on IDH-inhibitor therapy after 3 or more recurrences; previous lines of systemic therapy included temozolomide, bevacizumab, and lomustine. Five patients were treated with more than 1 cycle of IDH inhibitor, 2 patients with 8 cycles, and 1 patient with 18 cycles. Of the 11 treated patients, four had progression while on an IDH inhibitor, of which one patient died. IDH inhibitors were discontinued in two patients (due to headaches and abnormal liver enzymes). Median survival and progression free survival after IDH inhibitors were not reached. Conclusions: IDH inhibitors were started on patients with high-grade astrocytoma and oligodendroglioma after multiple recurrences and after receiving DNA-damage-inducing therapies. Prolonged responses were observed in 3 patients (one oligodendroglioma and two WHO grade 3 astrocytomas). Further investigation is needed to establish the role for IDH inhibitors in the treatment of high-grade gliomas.

Ginsenosides as Promising Therapeutic Agents for Glioma: Mechanisms of Action and Future Perspectives

Brain cancers, particularly gliomas, are a significant cause of mortality worldwide. Gliomas are primary tumors of the central nervous system (CNS) and are characterized by diverse clinical and biological features. Despite advancements in clinical approaches and surgical techniques, the treatment of high-grade gliomas still poses multiple challenges. This article focuses on a key active substance found in Panax ginseng called Ginsenosides. Ginsenosides belong to a specific class of triterpenoid saponins and have demonstrated various therapeutic effects, including neuroprotective, anticancer, anti-inflammatory, and neuroprotective functions. These compounds have shown potential in the treatment of gliomas and other cancers. Several pathways associated with ginsenosides, such as Rg3, Rh2, Rd, and Rb1, have been extensively studied, and these compounds have been proposed as potential targets in glioma treatment. The precise mechanisms of action of ginsenosides in gliomas are still being investigated, but their ability to modulate various signalling pathways and exert multiple therapeutic effects makes them promising candidates for further research and development. Clinical trials and additional studies are necessary to validate their therapeutic benefits and determine the optimal dosage, administration route, and potential combination with other treatment modalities. In summary, ginsenosides, the active compounds found in Panax ginseng, exhibit various therapeutic effects, including potential anti-cancer properties in gliomas. Their ability to modulate multiple pathways makes them promising targets for further research in the field of glioma treatment. However, more studies are required to establish their effectiveness and safety in clinical settings.

P.088 Wounded glioma syndrome: neurologic worsening in patients with subtotal resection in high-grade gliomas

Background: For treatment of high-grade gliomas (HGGs), subtotal resection (STR) may be preferred to minimize injury to eloquent areas. We aimed to characterize neurologic deficits developed in STR patients within the first month post-operatively and to establish a potential threshold for a safe volume of residual tumor to avoid neurological worsening. Methods: This is a single institution retrospective chart review, with 146 charts reviewed and 78 patients deemed eligible. Preoperative deficits and postoperative neurological deficits presenting prior to 1 month after surgery were captured. Imaging features such as tumour volume, edema, and other pertinent imaging characteristics were collected from preoperative and postoperative imaging. Results: Most patients that developed a postoperative deficit presented with motor deficits (55.1%), while only 1.3% of patients developed new or worsening tremor after surgery. On average, in patients with a new deficit, 26.5% of tumor was resected, and all patients had more than 19% of residual tumor. Conclusions: Postoperative neurologic deficits may develop after a subtotal resection when an average of 73.5% of tumor remains. The proposed threshold for tumor resection is greater than 26.5% to minimize the potential of neurologic worsening 1 month postoperatively.

Risk factors for nausea and vomiting requiring the daily administration of 5-HT3 receptor antagonists in radiotherapy combined with temozolomide for high-grade glioma.

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT3RA) for the first 3 days. The daily administration of 5-HT3RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT3RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT3RA) and resuming 5-HT3RA group (patients who resumed 5-HT3RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT3RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT3RA group following the resumption of 5-HT3RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT3RA according to the condition of each patient.