Glioblastoma in Adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) Consensus Review on Current Management and Future Directions.

Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society For Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase-wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies and viral therapies will be reviewed, as well as the current challenges and future directions for research.

[1]  P. Wen,et al.  Medical management of brain tumors and the sequelae of treatment. , 2015, Neuro-oncology.

[2]  M. Delorenzi,et al.  MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status , 2012, Acta Neuropathologica.

[3]  P. Wen,et al.  Thrombotic Complications in Gliomas , 2019, Seminars in Thrombosis and Hemostasis.

[4]  M. Weller,et al.  NKG2D-Based CAR T Cells and Radiotherapy Exert Synergistic Efficacy in Glioblastoma. , 2018, Cancer research.

[5]  Susan M. Chang,et al.  Letter: When Less is More: Dexamethasone Dosing for Brain Tumors. , 2019, Neurosurgery.

[6]  Lorenzo Trippa,et al.  The clinical trials landscape for glioblastoma: is it adequate to develop new treatments? , 2018, Neuro-oncology.

[7]  Tala,et al.  A metabolic function of FGFR3-TACC3 gene fusions in cancer , 2017, Nature.

[8]  T. Todo.  ATIM-14. RESULTS OF PHASE II CLINICAL TRIAL OF ONCOLYTIC HERPES VIRUS G47Δ IN PATIENTS WITH GLIOBLASTOMA , 2019, Neuro-Oncology.

[9]  S. Horvath,et al.  Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma , 2008, PLoS medicine.

[10]  A. Ranger,et al.  Familial syndromes associated with intracranial tumours: a review , 2013, Child's Nervous System.

[11]  E. Chiocca,et al.  Oncolytic Viruses in Cancer Treatment: A Review , 2017, JAMA oncology.

[12]  D. Busam,et al.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2008, Science.

[13]  Glyn Johnson,et al.  Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade. , 2004, AJNR. American journal of neuroradiology.

[14]  E. Shaw,et al.  A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. , 2007, International journal of radiation oncology, biology, physics.

[15]  Susan M. Chang,et al.  Patterns of care for adults with newly diagnosed malignant glioma. , 2005, JAMA.

[16]  C. Brennan,et al.  Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas , 2019, Clinical Cancer Research.

[17]  J. Sarkaria,et al.  Discordant In Vitro and In Vivo Chemopotentiating Effects of the PARP Inhibitor Veliparib in Temozolomide-Sensitive versus -Resistant Glioblastoma Multiforme Xenografts , 2014, Clinical Cancer Research.

[18]  T. Mikkelsen,et al.  Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients with prior antiangiogenic therapy , 2017, Neuro-oncology.

[19]  A. Friedman,et al.  Exercise behavior, functional capacity, and survival in adults with malignant recurrent glioma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  G. Sutherland,et al.  Prophylactic Anticonvulsants in Patients with Brain Tumour , 2003, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[21]  Ludmila V. Danilova,et al.  The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity , 2018, Cancer Immunology Research.

[22]  M. Prins,et al.  Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. , 2003, The New England journal of medicine.

[23]  T. Kuner,et al.  Glutamatergic synaptic input to glioma cells drives brain tumour progression , 2019, Nature.

[24]  Susan M. Chang,et al.  It is time to include patients with brain tumors in phase I trials in oncology. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Amy S Nowacki,et al.  Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. , 2014, Journal of neurosurgery.

[26]  J. Barnholtz-Sloan,et al.  CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. , 2019, Neuro-oncology.

[27]  A. Brandes,et al.  Nitrosoureas in the Management of Malignant Gliomas , 2016, Current Neurology and Neuroscience Reports.

[28]  M. J. van den Bent,et al.  OS10.1 Survival analysis of IDH wildtype astrocytomas with molecular features of glioblastoma, WHO grade IV , 2019, Neuro-Oncology.

[29]  Xiong-jie Fu,et al.  Diagnostic performance of DWI for differentiating primary central nervous system lymphoma from glioblastoma: a systematic review and meta-analysis , 2019, Neurological Sciences.

[30]  In-Hee Lee,et al.  Clonal evolution of glioblastoma under therapy , 2016, Nature Genetics.

[31]  Walter J Curran,et al.  Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Alexander Radbruch,et al.  Primary central nervous system lymphoma and atypical glioblastoma: multiparametric differentiation by using diffusion-, perfusion-, and susceptibility-weighted MR imaging. , 2014, Radiology.

[33]  Raymond Y Huang,et al.  Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma , 2018, Neuro-oncology.

[34]  Susan M. Chang,et al.  The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients. , 2019, Neuro-oncology.

[35]  L. Livi,et al.  Re-irradiation as salvage treatment in recurrent glioblastoma: A comprehensive literature review to provide practical answers to frequently asked questions. , 2018, Critical reviews in oncology/hematology.

[36]  Ji-Yong Um,et al.  Human glioblastoma arises from subventricular zone cells with low-level driver mutations , 2018, Nature.

[37]  M. Mehta,et al.  A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913 , 2018, Neuro-oncology.

[38]  Kristen L. Jones,et al.  Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model , 2015, Cancer Immunology Research.

[39]  P. Wen,et al.  Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial , 2019, Science Translational Medicine.

[40]  Gabriele Schackert,et al.  Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis. , 2019, Cancer cell.

[41]  Merrick I Ross,et al.  Neoadjuvant Immune Checkpoint Blockade in High-Risk Resectable Melanoma , 2018, Nature Medicine.

[42]  K. Hoang-Xuan,et al.  Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci , 2018, Acta Neuropathologica.

[43]  S. Ellsworth.  Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors , 2018, Advances in radiation oncology.

[44]  K. Aldape,et al.  Ketoconazole and Posaconazole Selectively Target HK2-expressing Glioblastoma Cells , 2018, Clinical Cancer Research.

[45]  E. Chiocca,et al.  Glioma virus therapies between bench and bedside. , 2014, Neuro-oncology.

[46]  K. Hoang-Xuan,et al.  Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. , 2014, The New England journal of medicine.

[47]  S. Rabkin,et al.  Oncolytic Viruses and Their Application to Cancer Immunotherapy , 2014, Cancer Immunology Research.

[48]  V. P. Collins,et al.  Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics , 2013, Proceedings of the National Academy of Sciences.

[49]  D. Osoba,et al.  Short‐Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma , 2017, The New England journal of medicine.

[50]  Anthony Asher,et al.  Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. , 2003, Journal of neurosurgery.

[51]  Costas D. Arvanitis,et al.  The blood–brain barrier and blood–tumour barrier in brain tumours and metastases , 2019, Nature Reviews Cancer.

[52]  E. Chiocca,et al.  Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. , 2015, Neuro-oncology.

[53]  K. Schalper,et al.  Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma , 2019, Nature Medicine.

[54]  T. Mikkelsen,et al.  Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  Jörg-Christian Tonn,et al.  Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. , 2011, Journal of neurosurgery.

[56]  A. Marson,et al.  Antiepileptic drugs as prophylaxis for post-craniotomy seizures. , 2015, The Cochrane database of systematic reviews.

[57]  Tzong-Shiue Yu,et al.  A restricted cell population propagates glioblastoma growth following chemotherapy , 2012, Nature.

[58]  James M. Brown,et al.  Automatic assessment of glioma burden: a deep learning algorithm for fully automated volumetric and bidimensional measurement , 2019, Neuro-oncology.

[59]  Nicolas Servant,et al.  Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. , 2015, The Lancet. Oncology.

[60]  Henry Brem,et al.  Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. , 2014, Neuro-oncology.

[61]  M. Prados,et al.  Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. , 2016, Neuro-oncology.

[62]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[63]  M. J. van den Bent,et al.  Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  Susan M. Chang,et al.  Barriers to Accrual and Enrollment in Brain Tumor Trials. , 2019, Neuro-oncology.

[65]  D. Neuberg,et al.  Intracranial hemorrhage with direct oral anticoagulants in patients with brain tumors , 2018, Journal of thrombosis and haemostasis : JTH.

[66]  S. Nelson,et al.  Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA , 2014, Science.

[67]  G. Reifenberger,et al.  European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. , 2017, The Lancet. Oncology.

[68]  Jill S Barnholtz-Sloan,et al.  Global incidence of malignant brain and other central nervous system tumors by histology, 2003–2007 , 2017, Neuro-oncology.

[69]  M. Mehta,et al.  NRG brain tumor specialists consensus guidelines for glioblastoma contouring , 2019, Journal of Neuro-Oncology.

[70]  P. Gutin,et al.  NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. , 2012, European journal of cancer.

[71]  Susan M. Chang,et al.  Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? , 2011, Neuro-oncology.

[72]  J. Castle,et al.  Actively personalized vaccination trial for newly diagnosed glioblastoma , 2018, Nature.

[73]  C. Balañà,et al.  A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond six cycles in patients with glioblastoma (GEINO 14-01). , 2020, Neuro-oncology.

[74]  R. Beroukhim,et al.  Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients , 2011, Journal of Neuro-Oncology.

[75]  Sankha S. Basu,et al.  Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  W. Wick,et al.  Glioblastoma in elderly patients: solid conclusions built on shifting sand? , 2018, Neuro-oncology.

[77]  Colin Watts,et al.  LONGITUDINAL MOLECULAR TRAJECTORIES OF DIFFUSE GLIOMA IN ADULTS , 2019, Nature.

[78]  Mark W. Dewhirst,et al.  Glioma stem cells promote radioresistance by preferential activation of the DNA damage response , 2006, Nature.

[79]  T. Cloughesy,et al.  Adult Glioblastoma. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  C. Decaestecker,et al.  Apparent Diffusion Coefficient and Cerebral Blood Volume in Brain Gliomas: Relation to Tumor Cell Density and Tumor Microvessel Density Based on Stereotactic Biopsies , 2008, American Journal of Neuroradiology.

[81]  J. Boxerman,et al.  Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape , 2017, Journal of Neuro-Oncology.

[82]  G. Reifenberger,et al.  cIMPACT-NOW update 5: recommended grading criteria and terminologies for IDH-mutant astrocytomas , 2020, Acta Neuropathologica.

[83]  Luke Vale,et al.  Intraoperative imaging technology to maximise extent of resection for glioma. , 2017, The Cochrane database of systematic reviews.

[84]  Susan M. Chang,et al.  Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients. , 2020, Neuro-oncology.

[85]  C. Brennan,et al.  Tracking Tumor Evolution in Glioma through Liquid Biopsies of Cerebrospinal Fluid , 2018, Nature.

[86]  C. Flowers,et al.  Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[87]  M. Weller,et al.  European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. , 2017, The Lancet. Oncology.

[88]  Raymond Y Huang,et al.  Imaging of Central Nervous System Tumors Based on the 2016 World Health Organization Classification. , 2020, Neurologic clinics.

[89]  Catherine J. Wu,et al.  Immunotherapy for glioblastoma: going viral , 2018, Nature Medicine.

[90]  J. Simes,et al.  Continuing or ceasing bevacizumab beyond progression in recurrent glioblastoma: an exploratory randomized phase II trial. , 2017, Neuro-oncology practice.

[91]  M. J. van den Bent,et al.  INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma , 2019, Neuro-oncology.

[92]  M. Weller,et al.  Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma , 2020, JAMA oncology.

[93]  M. Weller.  Where does O6‐methylguanine DNA methyltransferase promoter methylation assessment place temozolomide in the future standards of care for glioblastoma? , 2018, Cancer.

[94]  Xiuli Wang,et al.  Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. , 2016, The New England journal of medicine.

[95]  J Jack Lee,et al.  Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial , 2019, Nature Medicine.

[96]  D. Bigner,et al.  Systemic CTLA-4 Blockade Ameliorates Glioma-Induced Changes to the CD4+ T Cell Compartment without Affecting Regulatory T-Cell Function , 2007, Clinical Cancer Research.

[97]  D Riddoch,et al.  Neoplasms of the central nervous system. , 1977, The Practitioner.

[98]  S. Piantadosi,et al.  Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas , 1995, The Lancet.

[99]  Susan M. Chang,et al.  Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[100]  A. Jakola,et al.  The risk of getting worse: surgically acquired deficits, perioperative complications, and functional outcomes after primary resection of glioblastoma. , 2011, World neurosurgery.

[101]  Joshua M. Korn,et al.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2008, Nature.

[102]  Emanuel F Petricoin,et al.  Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma , 2018, Nature Genetics.

[103]  Paul S Mischel,et al.  Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. , 2012, Cancer discovery.

[104]  D. Merico,et al.  Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  Armin Giese,et al.  Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients , 2014, Acta Neurochirurgica.

[106]  E. Shaw,et al.  Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[107]  Jessica M. Rusert,et al.  Extrachromosomal oncogene amplification drives tumor evolution and genetic heterogeneity , 2017, Nature.

[108]  Marion Smits,et al.  Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. , 2015, Neuro-oncology.

[109]  Leland S. Hu,et al.  Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data , 2018, Neuro-oncology.

[110]  Till Acker,et al.  DNA methylation-based classification of central nervous system tumours , 2018, Nature.

[111]  K. Furie,et al.  A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors , 1996, Neurology.

[112]  E. Bruera,et al.  Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[113]  A. Brandes,et al.  AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma. , 2016, Neuro-oncology.

[114]  B. Jeremic,et al.  International Atomic Energy Agency Randomized Phase III Study of Radiation Therapy in Elderly and/or Frail Patients With Newly Diagnosed Glioblastoma Multiforme. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[115]  K. Hess,et al.  A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors. , 2013, Journal of neurosurgery.

[116]  Christopher A. Miller,et al.  Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy. , 2016, Cancer discovery.

[117]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[118]  Arthur André,et al.  Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma , 2019, Clinical Cancer Research.

[119]  K. Aldape,et al.  A randomized trial of bevacizumab for newly diagnosed glioblastoma. , 2014, The New England journal of medicine.

[120]  James M Provenzale,et al.  Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. , 2002, Radiology.

[121]  B. Meyer,et al.  Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. , 2016, Neuro-oncology.

[122]  P. Wen,et al.  Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A Bayesian Adaptive Platform Trial to Develop Precision Medicines for Patients With Glioblastoma , 2019, JCO precision oncology.

[123]  D. Henshaw,et al.  Brain Tumours: Rise in Glioblastoma Multiforme Incidence in England 1995–2015 Suggests an Adverse Environmental or Lifestyle Factor , 2018, Journal of environmental and public health.

[124]  G. Reifenberger,et al.  Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma , 2017, Neurology.

[125]  S. Khatua,et al.  Pediatric and adult H3 K27M-mutant diffuse midline glioma treated with the selective DRD2 antagonist ONC201 , 2019, Journal of Neuro-Oncology.

[126]  B. Nahed,et al.  Sequestration of T-cells in bone marrow in the setting of glioblastoma and other intracranial tumors , 2018, Nature Medicine.

[127]  David T. W. Jones,et al.  N2M2 (NOA-20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma. , 2018, Neuro-oncology.

[128]  L. Recht,et al.  Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors , 2000, Neurology.

[129]  N. Galldiks,et al.  The role of amino-acid PET in the light of the new WHO classification 2016 for brain tumors. , 2018, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[130]  M. Berger,et al.  Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[131]  H. Zentgraf,et al.  Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors , 2010, Brain pathology.

[132]  T. Mikkelsen,et al.  Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[133]  E. Chiocca,et al.  Strategies in Gene Therapy for Glioblastoma , 2013, Cancers.

[134]  P. Wen,et al.  Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma , 2018, Nature Medicine.

[135]  Y. Cheng,et al.  Durable Therapeutic Efficacy Utilizing Combinatorial Blockade against IDO, CTLA-4, and PD-L1 in Mice with Brain Tumors , 2014, Clinical Cancer Research.

[136]  G. Reifenberger,et al.  MGMT testing—the challenges for biomarker-based glioma treatment , 2014, Nature Reviews Neurology.

[137]  R. Vernhout,et al.  Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. , 2014, The Lancet. Oncology.

[138]  Steven J. M. Jones,et al.  Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma , 2014, Science.

[139]  M. Mehta,et al.  Glioblastoma: Radiation treatment margins, how small is large enough? , 2016, Practical radiation oncology.

[140]  Mariella G. Filbin,et al.  An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma , 2019, Cell.

[141]  Alyssa R. Richman,et al.  Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial , 2018, Nature.

[142]  J. Barnholtz-Sloan,et al.  Glioblastoma incidence rate trends in Canada and the United States compared with England, 1995-2015. , 2019, Neuro-oncology.

[143]  C. Bettegowda,et al.  Current state of immunotherapy for glioblastoma , 2018, Nature Reviews Clinical Oncology.

[144]  G. Reifenberger,et al.  Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. , 2015, Neuro-oncology.

[145]  R. Verhaak,et al.  Molecular Evolution of IDH Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[146]  Patrick Y Wen,et al.  Application of Novel Response/Progression Measures for Surgically Delivered Therapies for Gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group , 2012, Neurosurgery.

[147]  M. Jos,et al.  Effectiveness of antiepileptic prophylaxis used with supratentorial craniotomies: a meta-analysis , 1996, Seizure.

[148]  G. Reifenberger,et al.  cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” , 2018, Acta Neuropathologica.

[149]  Didier Frappaz,et al.  Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. , 2012, The Lancet. Oncology.

[150]  J. Sampson,et al.  Brain immunology and immunotherapy in brain tumours , 2019, Nature Reviews Cancer.

[151]  W. Mason,et al.  Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[152]  R. Stupp,et al.  Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082) , 2016, Clinical Cancer Research.

[153]  A. Iafrate,et al.  Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO classification of tumors of the central nervous system recommendations , 2017, Neuro-oncology.

[154]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[155]  Jill S Barnholtz-Sloan,et al.  Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution , 2015, Genome research.

[156]  M. Gilbert,et al.  Practical strategies for management of fatigue and sleep disorders in people with brain tumors. , 2012, Neuro-oncology.

[157]  G. Linette,et al.  CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges , 2018, Neuro-oncology.

[158]  Christopher M. Jackson,et al.  Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination , 2015, Clinical Cancer Research.

[159]  K. Mansfield,et al.  A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma , 2017, Science Translational Medicine.

[160]  H. Monyer,et al.  Emerging intersections between neuroscience and glioma biology , 2019, Nature Neuroscience.

[161]  S. Heiland,et al.  Automated quantitative tumour response assessment of MRI in neuro-oncology with artificial neural networks: a multicentre, retrospective study. , 2019, The Lancet. Oncology.

[162]  G. Reifenberger,et al.  MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial , 2015, Clinical Cancer Research.

[163]  Erwin G. Van Meir,et al.  Overcoming therapeutic resistance in glioblastoma: the way forward. , 2017, The Journal of clinical investigation.

[164]  M. J. van den Bent,et al.  Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma , 2016, Neuro-oncology.

[165]  P. Wen,et al.  Targeted molecular therapies against epidermal growth factor receptor: past experiences and challenges. , 2014, Neuro-oncology.

[166]  Marion Smits,et al.  Pseudoprogression of brain tumors , 2018, Journal of magnetic resonance imaging : JMRI.

[167]  Dima Suki,et al.  Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[168]  Christopher M. Jackson,et al.  Anti–PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM , 2016, Science Translational Medicine.

[169]  V. Rohde,et al.  Frequency of BRAF V600E mutations in 969 central nervous system neoplasms , 2016, Diagnostic Pathology.

[170]  C. Zimmer,et al.  A Second Course of Radiotherapy in Patients with Recurrent Malignant Gliomas: Clinical Data on Re-irradiation, Prognostic Factors, and Usefulness of Digital Biomarkers , 2019, Current Treatment Options in Oncology.

[171]  G. Reifenberger,et al.  Molecular targeted therapy of glioblastoma. , 2019, Cancer treatment reviews.

[172]  S. Goerdt,et al.  Macrophage activation and polarization: nomenclature and experimental guidelines. , 2014, Immunity.

[173]  R. Verhaak,et al.  Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target , 2018, The Journal of clinical investigation.

[174]  E. V. Van Allen,et al.  Genomic correlates of response to immune checkpoint blockade , 2019, Nature Medicine.

[175]  Q. Ostrom,et al.  Risk Factors For Childhood And Adult Primary Brain Tumors. , 2019, Neuro-oncology.

[176]  Troy Guthrie,et al.  Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[177]  M. Mehta,et al.  ACTR-34. SINGLE AGENT ONC201 IN PREVIOUSLY-TREATED, PROGRESSIVE ADULT H3 K27M-MUTANT GLIOMA , 2019, Neuro-Oncology.

[178]  J. Sarkaria,et al.  Temozolomide sensitizes MGMT-deficient tumor cells to ATR inhibitors. , 2019, Cancer research.

[179]  P. Wen,et al.  PL3.5 Efficacy and safety of selinexor in recurrent glioblastoma , 2019, Neuro-Oncology.

[180]  G. Fuller,et al.  PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma. , 2016, Cancer research.

[181]  A. Letai,et al.  Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma , 2017, Nature Medicine.

[182]  Shawn M. Gillespie,et al.  Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance. , 2017, Cell stem cell.

[183]  L. Held,et al.  Bevacizumab plus hypofractionated radiotherapy versus radiotherapy alone in elderly patients with glioblastoma: the randomized, open-label, phase II ARTE trial , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[184]  Toshinori Hirai,et al.  Usefulness of diffusion‐weighted MRI with echo‐planar technique in the evaluation of cellularity in gliomas , 1999, Journal of magnetic resonance imaging : JMRI.

[185]  Kathleen R. Lamborn,et al.  Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma. , 2010, Neuro-oncology.

[186]  Eilon D. Kirson,et al.  Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma , 2017 .

[187]  David T. W. Jones,et al.  Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis , 2018, Brain pathology.

[188]  J. C. Love,et al.  EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. , 2014, Cancer discovery.

[189]  D. Henshaw,et al.  Brain Tumours: Rise in Glioblastoma Multiforme Incidence in England 1995–2015 Suggests an Adverse Environmental or Lifestyle Factor , 2018, Journal of environmental and public health.

[190]  G. Mills,et al.  State-of-the-art strategies for targeting the DNA damage response in cancer , 2018, Nature Reviews Clinical Oncology.

[191]  M. Weller,et al.  ATIM-47. NIVOLUMAB VS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: EXPLORATORY ANALYSIS OF MGMT METHYLATION STATUS AND BASELINE CORTICOSTEROID USE , 2019, Neuro-Oncology.

[192]  A. Drilon.  TRK inhibitors in TRK fusion-positive cancers. , 2019 .

[193]  A. Iavarone,et al.  FGFR-TACC gene fusions in human glioma , 2016, Neuro-oncology.

[194]  K. Aldape,et al.  ACTR-21. A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIAL OF DEPATUXIZUMAB MAFODOTIN (ABT-414) IN EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AMPLIFIED (AMP) NEWLY DIAGNOSED GLIOBLASTOMA (nGBM) , 2019, Neuro-Oncology.

[195]  Shawn M. Gillespie,et al.  Electrical and synaptic integration of glioma into neural circuits , 2019, Nature.

[196]  R. Mirimanoff,et al.  Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. , 2009, The Lancet. Oncology.

[197]  R. Schreiber,et al.  Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion , 2011, Science.

[198]  W. Mason,et al.  Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma. , 2016, Neuro-oncology.

[199]  A. Bjørnerud,et al.  Clinical Value of Vascular Permeability Estimates Using Dynamic Susceptibility Contrast MRI: Improved Diagnostic Performance in Distinguishing Hypervascular Primary CNS Lymphoma from Glioblastoma , 2018, American Journal of Neuroradiology.

[200]  P. Wen,et al.  Corticosteroids for peritumoral edema: time to overcome our addiction? , 2016, Neuro-oncology.

[201]  Debyani Chakravarty,et al.  Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response , 2012, Proceedings of the National Academy of Sciences.

[202]  Radleigh G. Santos,et al.  A Randomized Double-Blind Placebo-Controlled Phase II Trial of Dendritic Cell Vaccine ICT-107 in Newly Diagnosed Patients with Glioblastoma , 2019, Clinical Cancer Research.

[203]  M. Malkin,et al.  PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma , 2010, Journal of thrombosis and haemostasis : JTH.

[204]  R. Stupp,et al.  Improving survival in molecularly selected glioblastoma , 2019, The Lancet.

[205]  W. Mason,et al.  Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[206]  S. Piantadosi,et al.  Immunosuppression in Patients with High-Grade Gliomas Treated with Radiation and Temozolomide , 2011, Clinical Cancer Research.

[207]  Ian Law,et al.  Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. , 2016, Neuro-oncology.

[208]  Anita Mahajan,et al.  Sleep-wake disturbance in patients with brain tumors , 2016, Neuro-oncology.

[209]  Susan M. Chang,et al.  Towards a standard pathological and molecular characterization of recurrent glioma in adults: a RANO effort. , 2019, Neuro-oncology.

[210]  P. Wen,et al.  Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study , 2019, Neuro-oncology.

[211]  Claus Belka,et al.  ESTRO-ACROP guideline "target delineation of glioblastomas". , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[212]  M. Gilbert,et al.  MGMT Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide: A Pooled Analysis of Four Clinical Trials , 2018, Clinical Cancer Research.

[213]  K. Kurian,et al.  Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells. , 2018, Cancer research.

[214]  Keith L. Ligon,et al.  Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies , 2007, Science.

[215]  T. Mikkelsen,et al.  Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy , 2017, Neuro-oncology.

[216]  D. O’Rourke,et al.  Clinical investigation of CAR T cells for solid tumors: lessons learned and future directions. , 2019, Pharmacology & therapeutics.

[217]  Timothy F Cloughesy,et al.  Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. , 2008, Neuro-oncology.

[218]  P. Wen,et al.  Clinical Relevance of Steroid Use in Neuro-Oncology , 2017, Current Neurology and Neuroscience Reports.

[219]  Sang Joon Kim,et al.  MRI as a diagnostic biomarker for differentiating primary central nervous system lymphoma from glioblastoma: A systematic review and meta‐analysis , 2019, Journal of magnetic resonance imaging : JMRI.

[220]  E. Chiocca,et al.  Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual? , 2018, Neuro-oncology.

[221]  Hao Xiong,et al.  Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study , 2017, Cancer Chemotherapy and Pharmacology.

[222]  D. Gerber,et al.  Management of venous thromboembolism in patients with primary and metastatic brain tumors. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[223]  Martin Glas,et al.  Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial , 2019, The Lancet.

[224]  Martin Klein,et al.  Lomustine and Bevacizumab in Progressive Glioblastoma , 2017, The New England journal of medicine.

[225]  Dima Suki,et al.  Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. , 2016, JAMA oncology.

[226]  T. Mikkelsen,et al.  Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma , 2016, Science Translational Medicine.

[227]  G. Hon,et al.  An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers. , 2016, Cancer cell.

[228]  Jens Frahm,et al.  Clinical proton MR spectroscopy in central nervous system disorders. , 2013, Radiology.

[229]  Timothy Heffron.  Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels. , 2018, Neuro-oncology.

[230]  L. Douw,et al.  The effect of modafinil on fatigue, cognitive functioning, and mood in primary brain tumor patients: a multicenter randomized controlled trial. , 2013, Neuro-oncology.

[231]  M. Taphoorn,et al.  Predictors of subjective versus objective cognitive functioning in patients with stable grades II and III glioma. , 2015, Neuro-oncology practice.

[232]  J. Pichler,et al.  A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma , 2014, Clinical Cancer Research.

[233]  M. Gilbert,et al.  Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. , 2011, International journal of radiation oncology, biology, physics.

[234]  G. Raskob,et al.  Edoxaban for the Treatment of Cancer‐Associated Venous Thromboembolism , 2017, The New England journal of medicine.

[235]  T. Mikkelsen,et al.  Phase I Study of GRN1005 in Recurrent Malignant Glioma , 2013, Clinical Cancer Research.

[236]  P. Wen,et al.  First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma , 2020, Clinical Cancer Research.

[237]  Raymond Y Huang,et al.  Mechanisms and therapeutic implications of hypermutation in gliomas , 2020, Nature.

[238]  Mitchel S Berger,et al.  An extent of resection threshold for newly diagnosed glioblastomas. , 2011, Journal of neurosurgery.

[239]  A. Holodny,et al.  MR Perfusion and MR Spectroscopy of Brain Neoplasms. , 2019, Radiologic clinics of North America.

[240]  Dirk Troost,et al.  Addressing diffuse glioma as a systemic brain disease with single-cell analysis. , 2012, Archives of neurology.

[241]  T. Mikkelsen,et al.  Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[242]  Steven R. Abram,et al.  First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma , 2018, Journal of Translational Medicine.

[243]  John H. Sampson,et al.  Recurrent Glioblastoma Treated with Recombinant Poliovirus , 2018, The New England journal of medicine.

[244]  J. Sarkaria,et al.  PARP Inhibitors for Sensitization of Alkylation Chemotherapy in Glioblastoma: Impact of Blood-Brain Barrier and Molecular Heterogeneity , 2019, Front. Oncol..

[245]  U. Röhrig,et al.  Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond , 2019, Nature Reviews Drug Discovery.

[246]  Ian Law,et al.  Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0 , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[247]  R. Bindra,et al.  Targeting DNA repair in gliomas. , 2019, Current opinion in neurology.

[248]  A. Brandes,et al.  A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma. , 2016, Neuro-oncology.

[249]  R. Stupp,et al.  Associations of anticoagulant use with outcome in newly diagnosed glioblastoma. , 2018, European journal of cancer.

[250]  A. Carson,et al.  Frequency, clinical associations, and longitudinal course of major depressive disorder in adults with cerebral glioma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[251]  Hugues Sicotte,et al.  Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors , 2017, Nature Genetics.

[252]  Stephen Broderick,et al.  Neoadjuvant PD‐1 Blockade in Resectable Lung Cancer , 2018, The New England journal of medicine.

[253]  Selene M. Virk,et al.  Epidemiology of Intracranial Gliomas. , 2018, Progress in neurological surgery.

[254]  David M. Hyman,et al.  BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[255]  S. Grossman,et al.  Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[256]  D. Neuberg,et al.  Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin. , 2017, Blood.

[257]  Michael E. Lassman,et al.  Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy , 2017, Cell.

[258]  P. Wen,et al.  Complications of therapy for venous thromboembolic disease in patients with brain tumors , 1993, Neurology.

[259]  G. Reifenberger,et al.  Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[260]  P. Brown,et al.  Investigating the Effect of Reirradiation or Systemic Therapy in Patients With Glioblastoma After Tumor Progression: A Secondary Analysis of NRG Oncology/Radiation Therapy Oncology Group Trial 0525. , 2018, International journal of radiation oncology, biology, physics.

[261]  K. Aldape,et al.  Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[262]  G. Reifenberger,et al.  Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. , 2012, The Lancet. Oncology.

[263]  Gary L. Gallia,et al.  TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal , 2013, Proceedings of the National Academy of Sciences.

[264]  P. Mischel,et al.  Altered cellular metabolism in gliomas — an emerging landscape of actionable co-dependency targets , 2019, Nature Reviews Cancer.

[265]  Steven J. M. Jones,et al.  Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma , 2016, Cell.

[266]  A. Brandes,et al.  Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. , 2019, The Lancet. Oncology.

[267]  R. Plummer,et al.  The DNA Damaging Revolution: PARP Inhibitors and Beyond. , 2019, American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

[268]  Benjamin M. Ellingson,et al.  Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials , 2017, Neurotherapeutics.

[269]  Susan M. Chang,et al.  Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. , 2014, Neuro-oncology.

[270]  G. Chiang,et al.  Imaging Glioblastoma Posttreatment: Progression, Pseudoprogression, Pseudoresponse, Radiation Necrosis. , 2019, Radiologic clinics of North America.

[271]  Yutaka Sato,et al.  Genetic Syndromes Associated with Central Nervous System Tumors. , 2017, Radiographics : a review publication of the Radiological Society of North America, Inc.

[272]  Pieter Wesseling,et al.  Reconstructing the molecular life history of gliomas , 2017, bioRxiv.

[273]  P. Wen,et al.  A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE) , 2019, Neuro-oncology.

[274]  R. Stupp,et al.  Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter--still a dilemma? , 2015, Neuro-oncology.

[275]  David T. W. Jones,et al.  Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. , 2012, Cancer cell.

[276]  C. Horbinski.  What do we know about IDH1/2 mutations so far, and how do we use it? , 2013, Acta Neuropathologica.

[277]  J. Debbins,et al.  Correlations between Perfusion MR Imaging Cerebral Blood Volume, Microvessel Quantification, and Clinical Outcome Using Stereotactic Analysis in Recurrent High-Grade Glioma , 2012, American Journal of Neuroradiology.

[278]  Rebecca A Betensky,et al.  Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. , 2011, Cancer cell.

[279]  William P. Accomando,et al.  Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC , 2018, Neuro-oncology.

[280]  D. Kondziolka,et al.  Mutant IDH1 and thrombosis in gliomas , 2016, Acta Neuropathologica.

[281]  R. Mirimanoff,et al.  MGMT gene silencing and benefit from temozolomide in glioblastoma. , 2005, The New England journal of medicine.

[282]  Brian M Alexander,et al.  Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE , 2017, Clinical Cancer Research.

[283]  D. Bigner,et al.  T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma , 2018, Clinical Cancer Research.

[284]  Ivan Babic,et al.  De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. , 2013, Cancer discovery.

[285]  Lorenzo Trippa,et al.  Design and Evaluation of an External Control Arm Using Prior Clinical Trials and Real-World Data , 2019, Clinical Cancer Research.

[286]  David T. W. Jones,et al.  Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge , 2014, Nature Reviews Cancer.

[287]  R. Verhaak,et al.  Delineation of MGMT Hypermethylation as a Biomarker for Veliparib-Mediated Temozolomide-Sensitizing Therapy of Glioblastoma. , 2015, Journal of the National Cancer Institute.

[288]  G. Lyman,et al.  Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[289]  K. Aldape,et al.  Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. , 2014, The Lancet. Oncology.

[290]  R. McLendon,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[291]  R. Stupp,et al.  Corticosteroids compromise survival in glioblastoma. , 2016, Brain : a journal of neurology.

[292]  Act Investigators.  Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial , 2017 .

[293]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[294]  C. Thompson,et al.  Metabolic Reprogramming in Brain Tumors. , 2017, Annual review of pathology.

[295]  D. Haussler,et al.  The Somatic Genomic Landscape of Glioblastoma , 2013, Cell.

[296]  F. Lieberman,et al.  Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial , 2017, JAMA.

[297]  Raymond Y Huang,et al.  Diffusion MRI Phenotypes Predict Overall Survival Benefit from Anti-VEGF Monotherapy in Recurrent Glioblastoma: Converging Evidence from Phase II Trials , 2017, Clinical Cancer Research.

[298]  D J Ruiter,et al.  Quantitative immunohistological analysis of the microvasculature in untreated human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor sections. , 1994, Journal of neurosurgery.

[299]  Richard A. Moore,et al.  Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy , 2017, Nature.

[300]  Jennifer S. Yu,et al.  Review of cranial radiotherapy-induced vasculopathy , 2015, Journal of Neuro-Oncology.

[301]  T. Hirai,et al.  Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity. , 2006, AJNR. American journal of neuroradiology.

[302]  J. Blay,et al.  ACTR-30. UPDATED EFFICACY AND SAFETY OF DABRAFENIB PLUS TRAMETINIB IN PATIENTS WITH RECURRENT/REFRACTORY BRAF V600E–MUTATED HIGH-GRADE GLIOMA (HGG) AND LOW-GRADE GLIOMA (LGG) , 2019, Neuro-Oncology.

[303]  John Wong,et al.  Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. , 2013, International journal of radiation oncology, biology, physics.

[304]  R. Bourgon,et al.  Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[305]  M. Sanson,et al.  Comparative assessment of 5 methods (methylation‐specific polymerase chain reaction, methylight, pyrosequencing, methylation‐sensitive high‐resolution melting, and immunohistochemistry) to analyze O6‐methylguanine‐DNA‐methyltranferase in a series of 100 glioblastoma patients , 2012, Cancer.

[306]  Christopher M. Jackson,et al.  Mechanisms of immunotherapy resistance: lessons from glioblastoma , 2019, Nature Immunology.

[307]  Tracy T Batchelor,et al.  A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. , 2006, Cancer research.

[308]  Naoya Hashimoto,et al.  Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. , 2015, The Lancet. Oncology.

[309]  R. Mirimanoff,et al.  Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG , 2015, Neuro-oncology.

[310]  A. Lassman,et al.  EPID-11. IDENTIFYING BARRIERS TO CLINICAL RESEARCH: A PILOT STUDY TO IMPROVE ACCESS AND ENROLLMENT TO NEURO-ONCOLOGY TRIALS AT COLUMBIA UNIVERSITY CENTER MEDICAL CENTER (CUMC) , 2017 .

[311]  Manfred Westphal,et al.  A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. , 2003, Neuro-oncology.

[312]  M. Mehta,et al.  ACTR-32. NRG ONCOLOGY RTOG 1205: RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VS. BEVACIZUMAB ALONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA , 2019, Neuro-Oncology.

[313]  J. Rich,et al.  Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer , 2019, Genes & development.

[314]  Shawn M. Gillespie,et al.  Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma , 2014, Science.

[315]  W. van Putten,et al.  Dose‐effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors , 1994, Neurology.

[316]  Christopher M. Jackson,et al.  Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model , 2014, PloS one.

[317]  Toshihiro Kumabe,et al.  Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis. , 2006, Radiology.

[318]  Katrina H. Smith,et al.  A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. , 2014, Neuro-oncology.

[319]  Edward F. Chang,et al.  Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. , 2017, Cancer cell.

[320]  Alona Muzikansky,et al.  Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[321]  Susan M. Chang,et al.  Response Assessment in Neuro-Oncology Clinical Trials. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[322]  K. Lange,et al.  Cognitive deficits before treatment among patients with brain tumors. , 2000, Neurosurgery.