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Radiotherapy delays malignant transformation and prolongs survival in patients with idh-mutant gliomas

Cancer Biology & Medicine 2022年第10期19卷 1477-1486页

作者： Yanwei Liu Huiyuan Chen Guanzhang Li Jing Zhang Kun Yao Chenxing Wu Shouwei Li Xiaoguang Qiu Department of Radiation Oncology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China National Clinical Research Center for Neurological Diseases Beijing 100070China Department of Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neuropathology Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China

Objective:idh-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAidhmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of idhmutant LGGs.Methods:We screened data for 108 patients with sAidhmut/G4 in the Chinese Glioma Genome Atlas who had initial idh-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from idh-mutant LGGs to sAidhmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with idh-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for idh-mutant/1p/19q-non-codeleted astrocytomas and idh-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;Pidh-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with idhmutant gliomas.

关键词： Lower-grade gliomas idh mutation radiotherapy malignant transformation survival

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Advances in the Immunotherapeutic Potential of Isocitrate Dehydrogenase mutations in Glioma

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Neuroscience Bulletin 2022年第9期38卷 1069-1084页

作者： Feng Tang Zhiyong Pan Yi Wang Tian Lan Mengyue Wang Fengping Li Wei Quan Zhenyuan Liu Zefen Wang Zhiqiang Li Brain Glioma Center and Department of Neurosurgery Wuhan University Zhongnan HospitalWuhan430071China Department of Physiology Wuhan University School of Basic Medical SciencesWuhan430071China

Isocitrate dehydrogenase(idh)is an essential metabolic enzyme in the tricarboxylic acid cycle(TAC).The high mutation frequency of the idh gene plays a complicated role in gliomas.In addition to affecting gliomas directly,mutations in idh can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways.idh mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion.In addition,idh mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells,also affecting their functioning.In this review,we summarize current knowledge about the effects of idh mutations as well as other gene mutations on the immune microenvironment of gliomas.We also describe recent preclinical and clinical data related to idh-mutant inhibitors for the treatment of gliomas.Finally,we discuss different types of immunotherapy and the immunotherapeutic potential of idh mutations in gliomas.

关键词： idh mutation Tumor immune microenvironment Immunotherapy Glioma

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PTPRZ1-METFUsion GENe(ZM-FUGEN)trial:study protocol for a multicentric,randomized,open-label phase II/III trial

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Chinese Neurosurgical Journal 2023年第4期9卷 315-319页

作者： Zhaoshi Bao Shouwei Li Liang Wang Bisi Zhang Peilong Zhang Hepeng Shi Xiaoguang Qiu Tao Jiang Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingChina Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China Department of Neurosurgery Tangdu HospitalFourth Military Medical UniversityXi’anChina Beijing Pearl Biotechnology Limited Liability Company BeijingChina Department of Radio‑Therapy Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Beijing Neurosurgical Institute Capital Medical UniversityBeijing 100070China Center of Brain Tumor Beijing Institute for Brain DisordersBeijing 100069China China National Clinical Research Center for Neurological Diseases Beijing 100050China

Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/idh mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or idh mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or idh mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with ***(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with ***(CTR20181664).

关键词： Glioblastoma idh mutation PTPRZ1-MET Vebreltinib Phase II/III Clinical trial

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Adult Diffuse Intrinsic Pontine Glioma:Clinical,Radiological,Pathological,Molecular Features,and Treatments of 96 patients

Adult Diffuse Intrinsic Pontine Glioma:Clinical,Radiological...

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第十六届中国医师协会神经外科医师年会

作者： Yi Wang Changcun Pan Mingguo Xie Pengcheng Zuo Xiaoou Li Guocan Gu Tian Li Zhuang Jiang Zhen Wu Junting Zhang Liwei Zhang Department of Neurosurgery Beijing Tiantan HospitalCapital Medical University Department of Neurosurgery Sanbo Brain Hospital China National Clinical Research Center for Neurological Diseases

Objective.Unlike its pediatric counterpart,adult diffuse intrinsic pontine glioma(DIPG) remains largely un-elucidated.The study examined the clinical,radiological,pathological,molecular,and clinical aspects of 96 adult DIPG.Methods.The National Brain Tumor Registry of China(2013/04-2019/12) was used to collect data on radiologically diagnosed adult DIPG patients.Survival analysis was conducted using the Kaplan–Meier Curve,univariate and multivariate Cox regression.The Chi-square test/Wilcoxon rank-sum test and multivariable logistic regression were used to examine the characteristics of long-term survival.Pidh1 mutations were 37.2% and 26.5%,respectively.All patients had a median overall survival(OS) of 19.5 months,with 1-,2-and 3-year survival rates of 67.0%,42.8%,and 36.0%,respectively.The patients with H3K27M showed a poorer prognosis than idh-mutant patients(Pidh-WT patients(P=0.002).The median OS of patients treated with RT+CT,RT/CT,and NO was 23.0 months,17.0 months,13.4 months respectively(P=0.097).The median OS of H3K27M patients who received the treatments and those who did not get treatments was 13.8 months and 7.5 months respectively(P=0.016).Short-term survival was related with cranial nerve palsy at diagnosis(OR,9.788;95%CI,2.242-42.731;P=0.002) and contrast enhancement in MRI(OR,7.741;95%CI,1.335-44.874;P=0.022).In patients with and without a pathological diagnosis,H3K27M(HR 8.084;95% CI 2.493-26.216;Pidh mutations.Despite the low prevalence,additional study is needed to be

关键词： adult diffuse intrinsic pontine glioma prognosis H3K27M idh mutation

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