scholarly journals The Biological Behavior of High-Grade Glioma in H3K27M Mutant Circumscribed Midline Gliomas

2021 ◽  
Author(s):  
Hainan Li ◽  
Jieyun Tan ◽  
Mingyao Lai ◽  
Wendan Chen ◽  
Minting Liu ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Clinicopathological Characteristics ◽  
Biological Behavior ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Prognostic Stratification ◽  
Grade 3 ◽  
Elder Adults ◽  
H3k27m Mutation

Abstract Purpose Due to the prognosis of circumscribed middle gliomas（CMGs）with H3K27M mutation is still unclear. This study explored the prognostic stratification of （CMGs） with H3K27M mutation.Methods: One hundred and sixty middle gliomas（MGs）were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and P53, and Sanger sequencing performed for IDH and H3 genes. The clinicopathological characteristics were reviewed and survival analysis performed.Results: 1. H3K27M mutation was associated with a poor prognosis (p = 0.00017) for brainstem gliomas, but not for thalamic gliomas (p = 0.3). In the elder adults (≥40 years), there was no correlation between H3K27M mutation and the prognosis for MGs (p = 0.49).2. For H3K27M mutant MGs, there was no difference in prognosis between diffuse midline gliomas (DMGs) and CMGs (p = 0.211), also between the CNS WHO grades.3. The prognosis of H3K27M mutant CMGs of CNS WHO grade 1 was worse than that of H3K27M wild-type CMGs (p = 0.0024), even worse than of DMGs without H3K27M mutation of CNS WHO grade 2(p = 0.0066). There was no significant difference in prognosis from DMGs with histological grades CNS WHO grade 3 and 4 (p = 0.46).Conclusions: The weight value of H3K27M affecting prognosis is affected by location and age. CMGs with H3K27M mutation have biological behavior similar to high-grade gliomas. It is recommended that Treatment management was referenced to high-grade glioma for CMGs with H3K27 mutation.

scholarly journals CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Rna Sequencing ◽  
Tumor Antigens ◽  
High Grade Glioma ◽  
Treatment Discontinuation ◽  
Sequencing Analysis ◽  
High Grade ◽  
Who Grade ◽  
Cytokine Levels ◽  
Grade 3

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.

Effect of temozolomide chronotherapy in patients with high-grade glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14525-e14525 ◽  
Author(s):  
Himachandana Atluri ◽  
Jian Li Campian ◽  
Grayson Talcott ◽  
Melissa Meyer ◽  
Emily Slat ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Biological Rhythms ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Well Being ◽  
Current Therapy ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Morning Administration

e14525 Background: High grade gliomas (HGG) (the most common being glioblastoma) are the most common primary CNS malignancy in adults. Mainstay of therapy is surgical resection followed by concurrent radiation and temozolomide (TMZ) followed by adjuvant TMZ. Unfortunately, prognosis remains poor and optimization of current therapy is critical. Chronotherapy is defined as improvement in treatment outcomes by maximizing treatment efficacy and minimizing toxicity by administering medications in accordance with biological rhythms of the patient. In a mouse model, there was greater anti-tumor efficacy during morning administration of TMZ. This trial was designed to determine the feasibility and potential clinical impact of chrono-therapeutically administering TMZ in patients with HGG. Methods: Adult patients ( > 18 years) with HGG (WHO Grade III/IV) were eligible. Patients were screened and consented prior to initiation of monthly TMZ therapy. Eligible patients were randomized to TMZ in the morning (AM) before 10AM or in the evening (PM) after 8PM. Pill diaries were recorded for drug administration time and compliance. Fact-Br Quality of Life (QoL) surveys were administered to patients at the time of enrollment in the trial and at the end of treatment to measure differences in QoL in both groups. Circadian rhythm was recorded by Actiwatch. Adverse events (AE), overall survival (OS) and progression free survival (PFS) were measured for each group. Results: At the time of submission, a total of 28 patients were evaluated. 15 patients were in AM group and 13 in PM group. It is feasible for participants to take TMZ per study assignment. There was no significant difference in the QoL based on the Fact-Br dataset in the four main categories of physical well-being, social/family well-being, functional well-being and emotional well-being. The Friedman’s two-way nonparametric ANOVA tests were used to analyze the differences across time points. Cytopenias are a known adverse effect of TMZ. There was a trend towards worsening lymphocyte counts in the AM group compared to PM group, although not statistically significant. There was no statistical significance in PFS or OS in patients with newly diagnosed glioblastoma. Conclusions: Chronotherapy with TMZ is feasible. A trend of worsening lymphocyte counts is noted in AM treatment group compared to PM group but was not statistically significant. No difference in OS or PFS was noted, although sample size was too small to effectively assess this. A larger study will need to be conducted to effectively assess the effect of chronotherapy on survival. Clinical trial information: NCT02781792.

scholarly journals Venous Thromboembolism and Intracranial Hemorrhage in Patients with High-grade Glioma

2020 ◽  
Author(s):  
Clara Borges ◽  
Carlota Lemos ◽  
Pedro Soares ◽  
Roberto Silva ◽  
Catarina Fernandes ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Intracranial Hemorrhage ◽  
Systemic Treatment ◽  
Performance Status ◽  
High Grade Glioma ◽  
Adult Patients ◽  
High Grade ◽  
Ecog Performance Status ◽  
Significant Difference ◽  
Grade 3

AbstractBackgroundPatients with high-grade glioma (HGG) are at increased risk of venous thromboembolism (VTE), throughout the course of disease. Prophylactic anticoagulation is not established among patients with HGG, outside of perioperative context, due to potential for intracranial hemorrhage (ICH) and the limited data available for predictive VTE scores in primary brain tumors. The aim of this study was to characterize VTE prevalence in adult patients with HGG and assess ICH risk during therapeutic anticoagulation.MethodsRetrospective analysis of patients diagnosed with HGG at our institution, between 2009 and 2018. All adult patients proposed to systemic treatment were included into this study. Exclusion criteria was anticoagulation previous to diagnosis. VTE was defined as any radiographic-confirmed thrombus in the venous system. Risk factors of interest for VTE and bleeding risk scores were analyzed by chi-squared test and multivariate logistic regression. Survival analysis was performed using Kaplan-Meier method.ResultsA total of 410 patients were included of whom 31 (7,8%) developed a VTE, including 22 deep vein, 6 pulmonary and 3 central venous thrombosis. Twenty-nine patients with VTE had a WHO grade 4 glioma and 2 patients had grade 3 (anaplastic astrocytoma and oligodendroglioma).In 22 cases, the VTE occurred during systemic treatment, more frequently during Temozolomide (n=15), followed by Irinotecan+Bevacizumab (n=6), Lomustine+Bevacizumab (n=1) and PCV (n=1). The median time between diagnosis and VTE was 10,11 months (95CI 6,46-14,79). Khorana score, age, ECOG performance status, smoking and obesity did not significantly differ in the VTE population. All VTE were initially treated with low molecular weight heparin (LMWH), of which 64.5% maintained LMWH, and the remainder switched to warfarin (19.4%) or to direct oral anticoagulant (16.1%). Six patients (19,4%) had spontaneous ICH under anticoagulation. Patients with grade 3 glioma (p=0,032) had significantly higher rates of ICH than grade 4. Patients with higher ECOG had significantly higher risk of ICH (OR 3,23 (95CI 1,18-8,81), p=0,022). HAS-BLED and ACCP bleeding scores were not associated with ICH. There was no significant difference in overall survival for TVE or ICH.ConclusionAccording to our data, ICH occurred in nearly 20% anticoagulated patients with HGG, as described in literature, and did not correlate with poorer prognosis. High ECOG performance status was an independent risk factor for ICH. Further effort towards better prediction models for VTE and ICH in HGG is warranted.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

scholarly journals A descriptive analysis of end-of-life discussions for high-grade glioma patients

2021 ◽  
Author(s):  
Ai Chikada ◽  
Sayaka Takenouchi ◽  
Yoshiki Arakawa ◽  
Kazuko Nin
Keyword(s):  
End Of Life ◽  
Health Care Providers ◽  
Patient Participation ◽  
High Grade Glioma ◽  
Team Approach ◽  
High Grade ◽  
Care Providers ◽  
Patient Goals ◽  
Significant Difference ◽  
Eol Care

Abstract Background End-of-life discussions (EOLDs) in patients with high-grade glioma (HGG) have not been well described. Therefore, this study examined the appropriateness of timing and the extent of patient involvement in EOLDs and their impact on HGG patients. Methods A cross-sectional survey was conducted among 105 bereaved families of HGG patients at a university hospital in Japan between July and August 2019. Fisher’s exact test and the Wilcoxon rank-sum test were used to assess the association between patient participation in EOLDs and their outcomes. Results In total, 77 questionnaires were returned (response rate 73%), of which 20 respondents replied with refusal documents. Overall, 31/57 (54%) participated in EOLDs at least once in acute hospital settings, and a significant difference was observed between participating and nonparticipating groups in communicating the patient’s wishes for EOL care to the family (48% vs 8%, P = .001). Moreover, >80% of respondents indicated that the initiation of EOLDs during the early diagnosis period with patients and families was appropriate. Most EOLDs were provided by neurosurgeons (96%), and other health care providers rarely participated. Additionally, patient goals and priorities were discussed in only 28% of the EOLDs. Patient participation in EOLDs was not associated with the quality of EOL care and a good death. Conclusions Although participation in EOLDs is relatively challenging for HGG patients, this study showed that participation in EOLDs may enable patients to express their wishes regarding EOL care. It is important to initiate EOLDs early on through an interdisciplinary team approach while respecting patient goals and priorities.

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

CTNI-22. A PHASE 0/1 ‘TRIGGER’ TRIAL OF RIBOCICLIB PLUS EVEROLIMUS IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi64-vi64
Author(s):  
Nader Sanai ◽  
An-Chi Tien ◽  
Jun Jiang ◽  
Yu-Wei Chang ◽  
Chelsea Pennington-Krygier ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Mtor Inhibition ◽  
Who Grade ◽  
Expansion Phase ◽  
Pik3ca Mutations ◽  
Pten Loss ◽  
Drug Concentrations ◽  
Phase 0 ◽  
Unbound Concentration

Abstract BACKGROUND mTOR activation is a mechanism of resistance in CDK4/6 targeting. We evaluated tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of combined CDK4/6 and mTOR inhibition in recurrent high-grade glioma (HGG) patients. METHODS Recurrent HGG patients with (1) intact RB, (2) CDKN2A/B deletion or CDK4/6 amplification, and (3) PTEN loss or PIK3CA mutations receive five days of presurgical ribociclib plus everolimus prior to resection at 2, 8 or 24 hours after the final dose. Beginning at 400mg QD ribociclib plus 2.5mg QD everolimus, six dose-escalations summit at 600mg QD plus 60mg QW. Gadolinium [Gd]-enhancing and nonenhancing tumor regions, CSF, and plasma are collected. Total and unbound drug concentrations are determined using validated LC-MS/MS methods. RB and S6 phosphorylation are compared to matched archival tissue. To select patients for a therapeutic expansion phase of combined drug therapy, the protocol includes a PK ‘trigger’ (i.e., for each drug, unbound concentration in Gd-nonenhancing tumor > 5-fold biochemical IC50) and a PD ‘trigger’ (i.e., for each tumor, > 30% decrease in pRB and pS6). RESULTS 21 patients with WHO Grade III (n=2) and IV (n=19) gliomas were enrolled into the Phase 0 component of the study. No dose-limiting toxicities were observed. In Gd-nonenhancing tumor regions, the median unbound concentration of ribociclib was 719 nM, whereas unbound everolimus tumor concentrations were undetectable. Across all dose-levels, 62% (13/21) and 22% (5/21) of tumors demonstrated decreased tumor RB and S6 phosphorylation, respectively. Tumor proliferation (MIB-1) was decreased in 67% (14/21) of all patients. No patients qualified for the therapeutic expansion phase. CONCLUSION In adult HGG, ribociclib achieves pharmacologically-relevant concentrations in Gd-nonenhancing tumor whereas everolimus exhibits no meaningful tumor penetration. These findings support further clinical development of ribociclib, but not everolimus, for the treatment of high-grade glioma patients.

scholarly journals High-grade glioma with anterior skull base erosion and intranasal extension: case report

2017 ◽  
Vol 126 (5) ◽  
pp. 1484-1487 ◽  
Author(s):  
Matthew T. Stib ◽  
Michael Johnson ◽  
Alan Siu ◽  
M. Isabel Almira-Suarez ◽  
Zachary Litvack ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Skull Base ◽  
Radiation Treatment ◽  
High Grade Glioma ◽  
Brain Parenchyma ◽  
Anterior Skull Base ◽  
High Grade ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment.

High-grade gliomas and molecular biology of neurosurgical oncology

2019 ◽  
pp. 89-106
Author(s):  
Stephen J Price ◽  
Harry Bulstrode ◽  
Richard Mair
Keyword(s):  
Molecular Markers ◽  
Who Classification ◽  
High Grade Glioma ◽  
High Grade ◽  
Optimal Management ◽  
Who Grade ◽  
Normal Human ◽  
Who Grade Iii ◽  
Grade Iii

The term high-grade glioma (HGG) encompasses a number of histological entities that are considered by the WHO Classification as WHO Grade III and IV tumours. They have traditionally been considered as having similar behaviour and had been treated in a similar manner but recent advances in our understanding of tumour biology have led to the identification of molecular markers that are now central to the classification of these tumours. Normal human cells develop into cancer cells through a stepwise accumulation of genomic and epigenomic alterations and this chapter considers the molecular markers of gliomas and explains their significance before going on to discuss the optimal management.

scholarly journals ACTR-59. A PHASE 1 STUDY OF BPM31510 PLUS VITAMIN K IN SUBJECTS WITH HIGH-GRADE GLIOMA THAT HAS RECURRED ON A BEVACIZUMAB-CONTAINING REGIMEN

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi27-vi27
Author(s):  
Lawrence Recht ◽  
Reena Thomas ◽  
Sophie Bertrand ◽  
Priya Yerballa ◽  
Gordon Li ◽  
...  
Keyword(s):  
Phase I ◽  
Vitamin K ◽  
Phase I Study ◽  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3

Abstract BACKGROUND High-grade gliomas (HGG) are characterized by dysregulated metabolism, utilizing glycolysis for energy production to support unrestricted growth. BPM 31510, an ubidecarenone (coenzyme Q10) containing lipid nanodispersion, causes a switch in cancer energy sourcing from glycolysis towards mitochondrial oxidative phosphorylation in vitro, reversing the Warburg effect and suggesting potential as an anti-tumor agent. The current study is a phase I study of BPM31510 + vitamin K in GB with tumor growth after bevacizumab (BEV). METHODS This is an open-label phase I study of BPM31510 continuous infusion with weekly vitamin K (10mg IM) in HGG patients using an mTPI design, starting at 110mg/kg, allowing for a single dose de-escalation and 2 dose-escalations. Patients had received first-line ChemoRadiation and were in recurrence following a BEV containing regimen. RESULTS 9 eligible and evaluable patients completed the 28 day DLT period. 8 patients had primary GB, 1 had anaplastic astrocytoma with confirmed pathologic transformation to GB. Median age was 55 years (27–67) and median KPS 70 (60–90) at enrollment. 4 patients were treated at the highest dose 171mg/kg, where there was a single DLT: Grade 3 AST & ALT. The most common grade 1–2 AEs possibly, probably or definitely related to drug were elevated AST, rash, and fatigue, each occurring in 3 patients. Median OS for 9 eligible/evaluable patients was 128 days (95% CI: 48–209) while PFS was 34 days (CI of mean 8.9). 3 patients are currently alive; 2 patients have survived >1 year. PK/PD data are being processed and will be presented. CONCLUSION This study confirms that BPM 31510 + vitamin K is safe and feasible in treatment-refractory HGG patients. Though this study demonstrates safety at 171mg/kg, the proposed dose for future studies in GB, based on additional pre-clinical and non-GB clinical data is 88mg/kg.

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