Treatment Of High-grade Gliomas Research Articles

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.

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.

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.

Endovascular Applications for the Management of High-Grade Gliomas in the Modern Era.

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

The Effect of Ketogenic Metabolic Therapy on Recurrent High-Grade Gliomas: Case Series

High-grade gliomas represent the most prevalent primary malignant brain tumors in the adult population. Despite extensive efforts dedicated to advance in therapeutic modalities, treatment options remain very limited in this field, leading to a worse prognosis for affected patients. Moreover, a considerable number of cases exhibit refractory disease following the initial management. Ketogenic Metabolic Therapy (KMT) has emerged as a promising adjunctive approach for recurrent high-grade gliomas, offering them a synergistic effect enhancement of the effectiveness of conventional therapies against this type of cancer. The underlying hypothesis relies on the use of high-fat, low-carbohydrate diet, with adequate protein content can potentially induce metabolic reprogramming in cancer cells. Currently, the use of KMT is on the rise and has shown positive effects on the control of selected neurological symptoms and improvements in patient’s quality of life. This is a descriptive observational multicenter study (case series) that includes patients with recurrent high-grade gliomas who underwent Ketogenic Metabolic Therapy (KMT) and were supplemented with a liquid ketogenic formula (in a 3:1 ratio) as a complementary treatment to the ongoing medical regimen for recurrence. The results show a positive impact on seizure control, as well as significant improvements in cognition, memory and functionality, as reported by patients and/or their families (caregivers). Regarding the disease status, assessed by the RANO criteria, the 12-month follow-up evaluation indicated stable disease in 55% and a partial response in 20% of cases. Although the results of this work are promising, more conclusive clinical data are still needed to support the use of KMT in the treatment of high-grade gliomas.

Treatment advances in high-grade gliomas.

High-grade gliomas (HGG) pose significant challenges in modern tumour therapy due to the distinct biological properties and limitations of the blood-brain barrier. This review discusses recent advancements in HGG treatment, particularly in the context of immunotherapy and cellular therapy. Initially, treatment strategies focus on targeting tumour cells guided by the molecular characteristics of various gliomas, encompassing chemotherapy, radiotherapy and targeted therapy for enhanced precision. Additionally, technological enhancements are augmenting traditional treatment modalities. Furthermore, immunotherapy, emphasising comprehensive tumour management, has gained widespread attention. Immune checkpoint inhibitors, vaccines and CAR-T cells exhibit promising efficacy against recurrent HGG. Moreover, emerging therapies such as tumour treating fields (TTFields) offer additional treatment avenues for patients with HGG. The combination of diverse treatments holds promise for improving the prognosis of HGG, particularly in cases of recurrence.

Retraction: The efficacy and adverse effects of anlotinib in the treatment of high-grade glioma: a retrospective analysis.

[This retracts the article DOI: 10.3389/fonc.2023.1095362.].

KRAS is a molecular determinant of platinum responsiveness in glioblastoma

BackgroundKRAS is the undisputed champion of oncogenes, and despite its prominent role in oncogenesis as mutated gene, KRAS mutation appears infrequent in gliomas. Nevertheless, gliomas are considered KRAS-driven cancers due to its essential role in mouse malignant gliomagenesis. Glioblastoma is the most lethal primary brain tumor, often associated with disturbed RAS signaling. For newly diagnosed GBM, the current standard therapy is alkylating agent chemotherapy combined with radiotherapy. Cisplatin is one of the most effective anticancer drugs and is used as a first-line treatment for a wide spectrum of solid tumors (including medulloblastoma and neuroblastoma) and many studies are currently focused on new delivery modalities of effective cisplatin in glioblastoma. Its mechanism of action is mainly based on DNA damage, inducing the formation of DNA adducts, triggering a series of signal-transduction pathways, leading to cell-cycle arrest, DNA repair and apoptosis.MethodsLong-term cultures of human glioblastoma, U87MG and U251MG, were either treated with cis-diamminedichloroplatinum (cisplatin, CDDP) and/or MEK-inhibitor PD98059. Cytotoxic responses were assessed by cell viability (MTT), protein expression (Western Blot), cell cycle (PI staining) and apoptosis (TUNEL) assays. Further, gain-of-function experiments were performed with cells over-expressing mutated hypervariable region (HVR) KRASG12V plasmids.ResultsHere, we studied platinum-based chemosensitivity of long-term cultures of human glioblastoma from the perspective of KRAS expression, by using CDDP and MEK-inhibitor. Endogenous high KRAS expression was assessed at transcriptional (qPCR) and translational levels (WB) in a panel of primary and long-term glioblastoma cultures. Firstly, we measured immediate cellular adjustment through direct regulation of protein concentration of K-Ras4B in response to cisplatin treatment. We found increased endogenous protein abundance and involvement of the effector pathway RAF/MEK/ERK mitogen-activated protein kinase (MAPK) cascade. Moreover, as many MEK inhibitors are currently being clinically evaluated for the treatment of high-grade glioma, so we concomitantly tested the effect of the potent and selective non-ATP-competitive MEK1/2 inhibitor (PD98059) on cisplatin-induced chemosensitivity in these cells. Cell-cycle phase distribution was examined using flow cytometry showing a significant cell-cycle arrest in both cultures at different percentage, which is modulated by MEK inhibition. Cisplatin-induced cytotoxicity increased sub-G1 percentage and modulates G2/M checkpoint regulators cyclins D1 and A. Moreover, ectopic expression of a constitutively active KRASG12V rescued CDDP-induced apoptosis and different HVR point mutations (particularly Ala 185) reverted this phenotype.ConclusionThese findings warrant further studies of clinical applications of MEK1/2 inhibitors and KRAS as ‘actionable target’ of cisplatin-based chemotherapy for glioblastoma.

Dose escalation with simultaneous integrated boost for un-methylated multiple glioblastoma.

Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial.

Review: therapeutic approaches for circadian modulation of the glioma microenvironment.

High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.

Safety and feasibility of intra-arterial delivery of teniposide to high grade gliomas after blood-brain barrier disruption: a case series.

This case series describes the safety and efficacy of superselective intra-arterial (IA) cerebral infusion of teniposide for the treatment of patients with glioma, to provide new ideas and methods for the treatment of high grade gliomas. 12 patients with glioma who were previously treated with standard therapy were treated with superselective IA cerebral infusion of teniposide. Patients received at least two cycles of treatment (one cycle: 150 mg/time, used for 1 day, repeated at 28 day intervals) after blood-brain barrier disruption. Patients received individualized treatment on the tumor location. The ophthalmic artery was bypassed during the super-selective arterial infusion. No significant differences in biochemical indexes and Karnofsky performance status (KPS) score were observed before and after treatment, and no evident adverse events occurred (P>0.05). In a recent response evaluation (August 2023), two (8%) patients presented with a complete response (16.7%), four had a partial response (33.3%), four had stable disease (33.3%), and two showed progressive disease (16.7%). The overall response rate and disease control rate were 50.0% and 83.3%, respectively. In addition, we described the detailed course of treatment in two patients. Case No 1 (recurrent tumor) and case No 2 (primary tumor) received six and three cycles of teniposide infusion, respectively. After treatment, the tumors of the patients were significantly reduced without evident adverse effects. This small series suggests that superselective IA cerebral infusion of teniposide may be a safe and effective therapy in the multimodal treatment of malignant glioma and warrants further study in larger prospective investigations.

QLTI-11. TIMELINE FROM INITIAL MRI TO INTERVENTION IN NEWLY DIAGNOSED HIGH GRADE GLIOMA

Abstract OBJECTIVE Prompt treatment of high-grade glioma is crucial for prolonging life. In an attempt to identify factors that lead to delays in treatment, we evaluated the amount of time between initial MRI and treatment start date for our patients with newly diagnosed high grade glioma. METHODS This was a retrospective chart review study. Adults over the age of 18 years of age with newly diagnosed high grade glioma were included if they were seen by the neuro-oncology department at Loma Linda University Medical Center. Reviewed charts were dated from November 2020 to August 2022. We evaluated the amount of time between initial MRI and several important milestones in the diagnosis and treatment of high grade glioma, including resection; biopsy results; neuro-oncology consult; radiation-oncology consult; date that chemotherapy was ordered, received by the patient, and initiated; and radiation therapy start date. RESULTS Twenty-two patients with new diagnosis of high-grade glioma were identified. Six patients were excluded due to complicated treatment courses involving outside facilities. Sixteen patients were included in the study. Thirteen patients (81%) had a diagnosis of glioblastoma, 2 (12%) had a diagnosis of diffuse midline glioma, and 1 (6%) had a diagnosis of anaplastic astrocytoma. The mean number of days between initial MRI and chemotherapy start date was 88. Prolonged timelines were seen in all analyzed metrics. CONCLUSIONS There is a significant delay in chemotherapy initiation for patients with high grade glioma at our facility. We also provide a framework for other institutions to evaluate their system processes in order to improve care delivery.

LTBK-09. RESULTS OF BMX-HGG STUDY: A MULTI-INSTITUTIONAL, RANDOMIZED PHASE 2 CLINICAL TRIAL OF CONCURRENT CHEMORADIATION WITH OR WITHOUT BMX-001 IN PATIENTS WITH NEWLY DIAGNOSED HIGH GRADE GLIOMA

Abstract BACKGROUND Standard treatment for high grade glioma (HGG) remains neurosurgical resection followed by concurrent radiation therapy (RT) and temozolomide (TMZ). Overall survival (OS) for GBM is roughly 12-16 months. RT is associated with cognitive and quality of life (QoL) impairments. Advances are needed to improve OS while mitigating injury to the normal brain. BMX-001 is a novel metalloporphyrin that radiosensitizes cancer cells and radioprotects normal tissue. METHODS This multi-institutional, open-label, phase 2 trial randomized newly diagnosed HGG patients to receive RT/TMZ with or without BMX-001 (NCT02655601). Both arms received 6 weeks RT/TMZ (75 mg/m2). BMX-001 was administered as a loading dose of 28 mg sc before RT, followed by 14 mg twice weekly for 8 weeks. Randomization was stratified by tumor grade and institution. Key eligibility criteria include histologically confirmed HGG, age ≥ 18 years, and KPS ≥ 70%. The primary endpoint was OS. Key secondary/exploratory outcomes included cognition, QoL, and white matter integrity using advanced imaging. OS evaluation occurred after 84 deaths when a 1-tailed logrank test (α=0.2) had 90% power to detect a hazard ratio of 0.63. Two interim analyses and a final analysis were conducted using an O’Brien-Fleming stopping boundary. RESULTS Of the 160 patients randomized, 72.5% had GBM, and 62.5% were male. Analyses focused on 145 patients who completed RT/TMZ (74 with BMX-001, 71 without BMX-001). Median OS of BMX-001+RT/TMZ group (31.3 [95% CI, 21.6, not reached] months) was longer than RT/TMZ group (24.7 [95% CI, 19.6-32.6] months), HR=0.735; p=0.079 (significant at the predefined α level). Common toxicities (Grade 1-2) attributed to BMX-001 were injection site reactions (64), tachycardia (24), and pruritus (17) with no related Grade 4-5. Diffusion tensor MR imaging indicated mitigation of dose-related white matter damage in BMX-001+RT/TMZ group. CONCLUSIONS BMX-001 is safe, and there is improved OS in HGG patients receiving BMX-001.

NCOG-41. REAL WORLD EXPERIENCE WITH TTFIELDS WITH EMPHASIS ON THERAPY COMPLIANCE

Abstract Tumor Treating Fields (TTF) therapy has emerged as a significant adjunctive component in the treatment of high-grade tumors following its validation in the EF-14 trial in 2017. The incorporation of TTF therapy, alongside cyclic temozolomide (TMZ) therapy, has demonstrated enhanced outcomes in terms of PFS and OS when the useage exceeds 18 hours per day (75% compliance rate). Post-hoc analysis of the EF-14 trial has demonstrated that compliance rates exceeding 90% are associated with an additional benefit. Given the cost-intensive nature and significant constraints associated with the therapy, our objective is to generate real-world data on compliance through a retrospective analysis at a high-throughput academic center. Between June 2015 and February 2022, a total of 115 patients were prescribed TTFields as pa rt of their treatment for high-grade glioma. Mean age was 50y and mean preoperative Karnofsky Index 80-90. The average duration of therapy was 8 months. The majority of patients (74%) initiated therapy concurrently with 1st-line treatment, while only 25% managed to start concomitant to the first cycle of temozolomide. 16.7% started TTFields in the 2nd-line and 9.3% in the 3rd-line setting. Thirteen patients discontinued TTFields treatment within the first 3 months and were consequently excluded from further compliance analysis. Across the study cohort, the median compliance rate was 72% (SD 22%), with an average of 41 days of breaks observed. Compliance was highest during the first 3 cycles, with rates of 79%, 73%, and 72%, respectively. Linear regression analysis did not identify any predictors of compliance, including age at surgery, timing of therapy, duration of therapy, gender, and preoperative Karnofsky Index. These findings highlight the importance of monitoring and promoting adherence to TTFields therapy to maximize its potential benefits in the management of high-grade gliomas. Further strategies are warranted to expedite the start of therapy and improve long-term compliance.

13 Do No Harm: Does Repeated Surgical Resections for Management of HighGrade Glioma Recurrence Impact Quality of Life?

Objective:High-grade gliomas are aggressive and infiltrate surrounding brain parenchyma, making gross total resection difficult, and despite aggressive treatment, its recurrence is inevitable (Zhou et al., 2016). Repeated tumor resections have been shown to increase survival (Chaichana et al., 2013) but the cost of doing so on quality of life (QoL) and functioning is not known. To address this gap, we compared changes in QoL using the Functional Assessment of Cancer Therapy-Brain questionnaire (FACT-Br; Weitzner et al., 1995) in high-grade glioma patients undergoing first versus repeat surgical resection.Participants and Methods:Thirty-three patients with high-grade gliomas (mean age=52, 54.5% female) that underwent tumor resection and completed comprehensive neuropsychological evaluations that included FACT-Br pre-operative and at 2-week follow up were included in this study. FACT-Br assesses four QoL domains: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), and functional well-being (FWB). A subscale total score was computed for each domain, and these subscale scores were summed to compute a total score for overall QoL. Difference scores were computed for each subscale score and total score by subtracting patients’ pre-operative rating from post-operative rating. More positive scores indicate lesser perceived changes of QoL post-operatively. One-way MANOVA analysis was run to compare the difference scores between patients that underwent first resection and those that underwent repeated resection.Results:There was no significant difference in perceived changes of overall QoL between the two groups of patients. However, patients with previous resection reported larger decline in perceived physical well-being compared to patients without previous resection (F(1,30)=99.93, p&lt;.05,partial n2=.16). There were no significant differences in other QoL domains between the two groups.Conclusions:We showed no differences in perceived changes across most QoL domains in patients undergoing repeat versus first surgical resection for treatment of high-grade glioma, suggesting that repeated resections may be a viable strategy in managing tumor recurrences. Specifically, there were no group differences in social, emotional, and functional well-being pre-to postoperatively. However, patients with previous resection reported significantly larger decline in their perceived physical well-being than those without any previous resection. A possible explanation is that patients with previous resection underwent adjuvant therapies (e.g., radiation therapy, chemotherapy) and experienced tumor progression necessitating reoperation, which could have made them more vulnerable to the physical impacts of surgery. Our findings are encouraging and may provide useful insight to guide treatment strategies and patient’s decision making to optimize both surgical and functional outcomes.

NEED OF THE HOUR TO USE MR PERFUSION TO DIFFERENTIATE BETWEEN RADIATION NECROSIS AND TUMOUR RECURRENCE IN KNOWN GLIOMA PATIENTS

Conventional MR imaging may be non-specific in diagnosing low-grade gliomas. Better modalities are used nowadays including MRS (spectroscopy), perfusion, and diffusion-weighted imaging (1).&#x0D; MR perfusion is better than CT perfusion in various aspects. MR perfusion does not expose the patient to ionizing radiation. CT perfusion, on the other hand, can be harmful if the patient receives repeated doses. However, CT perfusion may be more readily available in emergency settings and can be quicker to perform than MR perfusion, which requires a longer acquisition time. CT perfusion can also provide more precise measurements of blood flow in small vessels than MR perfusion. Ultimately, the choice between MR perfusion and CT perfusion depends on the specific clinical situation and the preferences of the medical team.&#x0D; Perfusion MRI studies have become an increasingly important tool in the management of high-grade gliomas as well. Perfusion MRI allows clinicians to assess the vascularity of these tumors, providing information on tumor grade, response to treatment, and prognosis. Perfusion imaging can be performed using various techniques, including dynamic susceptibility contrast (DSC) MRI and arterial spin labeling (ASL) MRI. DSC-MRI is the most commonly used technique, and it provides information on cerebral blood volume (CBV) and cerebral blood flow (CBF) in the tumor and surrounding tissue. ASL-MRI, on the other hand, measures blood flow by magnetically labeling arterial blood water protons and can provide information on tumor perfusion without the use of contrast agents. Overall, perfusion MRI studies have demonstrated significant potential for improving the diagnosis, management, and prognosis of high-grade gliomas. MR brain perfusion is a type of imaging technique that can be used to differentiate between radiation-related changes and tumor recurrence in patients who have undergone radiation therapy for brain tumors. (2).&#x0D; &#x0D; Tumor resection followed by chemoradiation remains the current criterion standard treatment for high-grade gliomas. Radiation therapy can cause changes in the brain that may appear similar to tumor recurrence on conventional MRI scans. However, MR brain perfusion can detect differences in blood flow patterns between tumor tissue and normal brain tissue, which can help to differentiate between radiation-related changes/necrosis and tumor recurrence (3).&#x0D; Every institute should start using MR perfusion studies to differentiate these. This will eventually help in patient correct diagnosis and reduction in morbidity and mortality.&#x0D; Key-words:&#x0D; Gliomas, MR Perfusion, CT Perfusion, Tumour Recurrence, Radiation Necrosis.&#x0D; &#x0D; Conflict of Interest: All authors declare no conflict of interest.&#x0D; &#x0D; Funding Role: None to declare.&#x0D; &#x0D; Author Contributions: All authors contributed equally to the drafting of study.&#x0D; &#x0D; Ethical Statement: Written as per the ethical guidelines of hospital board.&#x0D; &#x0D;

Evaluation of the Effectiveness of Boron Neutron Capture Therapy with Iodophenyl-Conjugated closo-Dodecaborate on a Rat Brain Tumor Model.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron used by the carrier compounds-such as 4-borono-L-phenylalanine (L-BPA)-have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BNCT mediated by BC-IP showed significant survival improvement in glioma-bearing rats compared to controls (not treated animals and neutrons only). These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.