The Diagnostic Value of Preoperative Hematology Makers in the Classification and Molecular Subtypes of Newly Diagnosed High-Grade Gliomas

Abstract Objective The purpose of our study is to explore the diagnostic value of the single and combined hematological maker for the classification and isocitrate dehydrogenase (IDH)-1/2 mutations molecular subtypes of high-grade gliomas (HGGs). Methods A total of 354 newly diagnosed HGGs patients were included in this study. Firstly, we compared the levels of hematology indicators in the classification and molecular subtypes of HGGs. Next, the correlation between the levels of hematology indicators with basic clinical features was analyzed. Finally, the diagnostic value of the single and combined hematology indicator for identifying the classification and molecular subtypes from HGGs was performed. Results The level of fibrinogen (FIB) was higher in higher grade gliomas and glioblastoma multiforme IDH wild type (GBM IDH-wt). Nutrition-related indicators such as serum albumin (ALB), albumin/globulin ratio (AGR), and prognostic nutrition index (PNI) were negatively correlated with age, whereas FIB was positively associated with age. Compared with women, men with GBM had significantly higher AGR and lower serum globulin (GLOB). We found that the best single and combined indicator for identifying GBM and GBM IDH-wt from HGGs were FIB [0.595 (0.519–0.672) and 0.615 (0.546–0.684)] and age + FIB [0.712 (0.642–0.783) and 0.726 (0.662–0.791)], respectively. Conclusions Preoperative hematological indicators have high diagnostic value for GBM and GBM IDH-wt from HGGs, especially FIB combined age.

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The Diagnostic Value of Preoperative Hematology Makers in the Classification and Molecular Subtypes of Newly Diagnosed High-Grade Gliomas

10.21203/rs.3.rs-569387/v1 ◽

2021 ◽

Author(s):

Xin Jia ◽

Yixuan Zhai ◽

Fengdong Yang ◽

Yiming Wang ◽

Shuxin Wei ◽

...

Keyword(s):

Molecular Subtypes ◽

Diagnostic Value ◽

High Grade ◽

Newly Diagnosed ◽

Wild Type ◽

Serum Globulin ◽

Lower Serum ◽

High Grade Gliomas ◽

Hematological Indicators ◽

Prognostic Nutrition Index

Abstract Purpose: The purpose of our study is to explore the diagnostic value of the single and combined hematological maker for the classification and isocitrate dehydrogenase (IDH)-1/2 mutations (IDH) molecular subtypes of high-grade gliomas (HGGs).Methods: A total of 354 newly diagnosed HGGs patients were included in this study. Firstly, we compared the levels of hematology indicators in the classification and molecular subtypes of HGGs. Next, the correlation between the levels of hematology indicators with basic clinical features was analyzed. Finally, the diagnostic value of the single and combined hematology indicator for identifying the classification and molecular subtypes from HGGs was performed.Results: The level of fibrinogen (FIB) was higher in higher grade gliomas and glioblastoma multiforme IDH wild type (GBM IDH-wt). Nutrition-related indicators such as serum albumin (ALB), albumin/globulin ratio (AGR), and prognostic nutrition index (PNI) were negatively correlated with age, whereas FIB was positively associated with age. Compared with women, men with GBM had significantly higher AGR and lower serum globulin (GLOB). We found that the best single and combined indicator for identifying GBM and GBM IDH-wt from HGGs were FIB [0.595 (0.519-0.672) and 0.615 (0.546-0.684)] and age+FIB [0.712 (0.642-0.783) and 0.726 (0.662-0.791)], respectively.Conclusions: Preoperative hematological indicators have high diagnostic value for GBM and GBM IDH-wt from HGGs, especially FIB combined age.

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Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: Results of a phase 1 clinical trial

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa154 ◽

2020 ◽

Author(s):

Gary L Gallia ◽

Matthias Holdhoff ◽

Henry Brem ◽

Avadhut D Joshi ◽

Christine L Hann ◽

...

Keyword(s):

Dose Escalation ◽

Plasma Levels ◽

Phase 1 ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

High Grade ◽

Newly Diagnosed ◽

Kaplan Meier ◽

High Grade Gliomas ◽

Expansion Cohort

Abstract Background Mebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers. Methods A single center dose escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas (HGG) in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose escalation levels were 25, 50, 100 and 200 mg/kg/day of oral mebendazole. A 15-patient expansion cohort was conducted at the maximum tolerated dose of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8 and 16 weeks. Results Twenty-four patients (18 glioblastoma, 6 anaplastic astrocytoma) were enrolled with median age of 49.9 years. Four patients (at 200 mg/kg) developed elevated grade 3 ALT and/or AST after one month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan Meier analysis showed a 21-month median survival with 43% of patients alive at two years and 25% at 3 and 4 years. Median progression free survival (PFS) from the date of diagnosis for 17 patients taking more than one month of mebendazole was 13.1 months (95% Confidence Interval: 8.8 to 14.6 months) but for seven patients who received less than one month of mebendazole PFS was 9.2 months (95% CI: 5.8 -13.0 months). Conclusion Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole’s efficacy in patients with HGG.

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Prognostic value of modified systemic inflammatory score in patients with newly diagnosed high-grade gliomas

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2020.106428 ◽

2021 ◽

Vol 201 ◽

pp. 106428

Author(s):

Tian Xie ◽

Xiaoyu Guo ◽

Hao Duan ◽

Zhenqiang He ◽

Yonggao Mou

Keyword(s):

Prognostic Value ◽

High Grade ◽

Newly Diagnosed ◽

Inflammatory Score ◽

High Grade Gliomas

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EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

Neuro-Oncology ◽

10.1093/neuonc/noaa222.141 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii307-iii307

Author(s):

Mariko DeWire ◽

James Leach ◽

Christine Fuller ◽

Peter de Blank ◽

Trent Hummel ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Single Agent ◽

Maximum Tolerated Dose ◽

Pharmacokinetic Studies ◽

High Grade ◽

Newly Diagnosed ◽

High Grade Gliomas ◽

Grade 3 ◽

Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

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