Highlights
- •Low grade gliomas (LGG) traditionally categorised as indolent or ‘benign’ lesions.
- •Surveillance imaging has been the mainstay for incidental or asymptomatic LGG.
- •Such patients are monitored often without being referred to a Neuro-oncology unit.
- •New biological knowledge and validated treatment options have advanced LGG care.
- •Thus, proactive LGG management, with early neurosurgical referral, is essential.
Abstract
The discovery of IDH1/2 (isocitrate dehydrogenase) mutation in large scale, genomewide
mutational analyses of gliomas has led to profound developments in understanding tumourigenesis,
and restructuring of the classification of both high and low grade gliomas. Owing
to this progress made in the recognition of molecular markers which predict tumour
behavior and treatment response, the increasing importance of adjuvant treatments
such as chemo- and radiotherapy, and the tremendous advances in surgical technique
and intraoperative monitoring which have facilitated superior extents of resection
whilst preserving neurological functioning and quality of life, contemporary management
of low grade glioma (LGG) has switched from a passive, observant approach to a more
active, interventional one. Furthermore, this has implications for the manner in which
patients with incidentally discovered and/or asymptomatic LGG are managed, and this
review of the biological behaviour of LGG, as well as its clinical investigation and
management, should act as a timely reminder to all clinicians of the importance of
referring LGG patients early to a surgical neuro-oncologist who is not only familiar
and acquainted with the vagaries of this disease process, but who, in addition, is
devoted to delivering care to these patients with the support of a multi-disciplinary
clinical decision-making unit, comprising medical neuro-oncologists, radiation oncologists
and allied health professionals.
Keywords
Abbreviations:
1p19q (short arm of chromosome 1, long arm of chromosome 19), 2-HG (2-Hydroxyglutarate), α-KG (α (Alpha)-Ketoglutarate), ATRX (Alpha Thalassemia/mental Retardation syndrome X-linked), BBB (Blood-brain barrier), CDKN2A (Cyclin-Dependent Kinase inhibitor 2A), CDK4NA (Cyclin-Dependent Kinase inhibitor 4A), CNS (Central Nervous System), CNV (Copy Number Variations), CT (Computed Tomography), DNA (Deoxyribonucleic acid), DWI (Diffusion Weighted Imaging), EANO (European Association of Neuro-oncology), EGFR (Epithelial Growth Factor Receptor), EOR (Extent of resection), EORTC (European Organisation for Research and Treatment of Cancer), FET (Fluoroethyltyrosine), FLAIR (Fluid Attenuated Inversion Recovery), H3F3A (Histone H3.3A), HGG (High Grade Glioma), HR (Hazard ratio), IDH (Isocitrate Dehydrogenase), IDHmut (IDH mutant), IDHwt (IDH wildtype), IGFBP2 (Insulin-like Growth Factor Binding Protein 2), KPS (Karnofsky Performance Score), LGG (Low Grade Glioma), MGMT (O-6-methylguanine-DNA methyltransferase), MR(I) (Magnetic Resonance (Imaging)), MRS (Magnetic Resonance Spectroscopy), NOS (Not otherwise specified), OS (Overall survival), PCV (Procarbazine/Lomustine/Vincristine), PET (Positron Emission Tomography), Pi3k (Phosphatidylinositol 3-Kinase), PFS (Progression-free survival), PTEN (Phosphastase and Tensin homologue), PWI (Perfusion Weighted Imaging), RTV (Residual Tumour Volume), TCGA (The Cancer Genome Atlas), TERT (Telomerase Reverse Transcriptase), TP53 (Tumour Protein 53), UCSF (University of California San Francisco), WHO (World Health Organisation)To read this article in full you will need to make a payment
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References
- The 2016 World Health Organization classification of tumors of the central nervous system: a summary.Acta Neuropathol. 2016; 131: 803-820
- IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas.Am J Pathol. 2009; 174: 1149-1153
- Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin.J Clin Oncol. 2011; 29: 4482-4490
- IDH1 and IDH2 mutations in gliomas.N Engl J Med. 2009; 360: 765-773
- Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis.Acta Neuropathol. 2010; 120: 719-729
- Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities.Acta Neuropathol. 2015; 130: 407-417
Cancer Genome Atlas Research N, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481–98.
- IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.Acta Neuropathol. 2015; 129: 867-873
- Response assessment in neuro-oncology working group and european association for neuro-oncology recommendations for the clinical use of PET imaging in gliomas.Neuro Oncol. 2016; 18: 1199-1208
- The role of imaging in the management of adults with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.J Neurooncol. 2015; 125: 457-479
- Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials.Neuro Oncol. 2015; 17: 1188-1198
- (18)F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naive gliomas: a cross-sectional study.J Neurooncol. 2018; 139: 399-409
- The silent phase of diffuse low-grade gliomas. Is it when we missed the action?.Acta Neurochir (Wien). 2013; 155: 2237-2242
- Silent diffuse low-grade glioma: toward screening and preventive treatment?.Cancer. 2014; 120: 1758-1762
- Continuous growth of mean tumor diameter in a subset of grade II gliomas.Ann Neurol. 2003; 53: 524-528
- Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas.Ann Neurol. 2006; 60: 380-383
- Dynamic history of low-grade gliomas before and after temozolomide treatment.Ann Neurol. 2007; 61: 484-490
- Inter- and intrapatients comparison of WHO grade II glioma kinetics before and after surgical resection.Neurosurg Rev. 2010; 33: 91-96
- Intraoperative subcortical stimulation mapping of language pathways in a consecutive series of 115 patients with Grade II glioma in the left dominant hemisphere.J Neurosurg. 2008; 109: 461-471
- Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas.J Clin Oncol. 2008; 26: 1338-1345
- Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients: clinical article.J Neurosurg. 2012; 117: 1039-1052
Mohammadi AM, Sullivan TB, Barnett GH, Recinos V, Angelov L, Kamian K, et al. Use of high-field intraoperative magnetic resonance imaging to enhance the extent of resection of enhancing and nonenhancing gliomas. Neurosurgery 2014;74:339–48; discussion 49; quiz 49–50.
- Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis.J Clin Oncol. 2012; 30: 2559-2565
- The, “onco-functional balance” in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life.Acta Neurochir (Wien). 2013; 155: 951-957
- Supratotal resection of diffuse gliomas - an overview of its multifaceted implications.Neurochirurgie. 2017; 63: 243-249
- Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas.Neuro Oncol. 2014; 16: 914-923
- An integrated genomic analysis of human glioblastoma multiforme.Science. 2008; 321: 1807-1812
- Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas.Acta Neuropathol. 2009; 118: 469-474
- Analysis of the IDH1 codon 132 mutation in brain tumors.Acta Neuropathol. 2008; 116: 597-602
- IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas.Oncotarget. 2015; 6: 30295-30305
- IDH wild-type WHO grade II diffuse low-grade gliomas. A heterogeneous family with different outcomes. Systematic review and meta-analysis.Neurosurg Rev. 2018;
- Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.Cancer Cell. 2010; 17: 98-110
- Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases.Cancer Cell. 2011; 19: 17-30
- IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.Nature. 2012; 483: 479-483
- IDH mutation impairs histone demethylation and results in a block to cell differentiation.Nature. 2012; 483: 474-478
- Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma.Oncotarget. 2012; 3: 1194-1203
- Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.Oncotarget. 2012; 3: 709-722
- IDH mutation status trumps the Pignatti risk score as a prognostic marker in low-grade gliomas.J Neurooncol. 2017; 135: 273-284
- Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors.N Engl J Med. 2015; 372: 2499-2508
- IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.Acta Neuropathol. 2015; 129: 585-596
- IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma.Clin Cancer Res. 2012; 18: 2490-2501
- IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas.Clin Cancer Res. 2009; 15: 6002-6007
- Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.Cancer Cell. 2012; 22: 425-437
- IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma.Oncotarget. 2015; 6: 30232-30238
- IGFBP2 expression predicts IDH-mutant glioma patient survival.Oncotarget. 2017; 8: 191-202
- DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status.Acta Neuropathol Commun. 2015; 3: 34
- Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis.J Neurooncol. 2017; 133: 183-192
- Genetic and epigenetic features of rapidly progressing IDH-mutant astrocytomas.J Neuropathol Exp Neurol. 2018; 77: 542-548
- Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.Acta Neuropathol. 2018; 136: 153-166
- Radial expansion rates and tumor growth kinetics predict malignant transformation in contrast-enhancing low-grade diffuse astrocytoma.CNS Oncol. 2015; 4: 247-256
- Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas.Neuro Oncol. 2014; 16: 1100-1109
- Acute progression of untreated incidental WHO Grade II glioma to glioblastoma in an asymptomatic patient.J Neurosurg. 2016; 124: 141-145
- IDH mutation and 1p19q codeletion distinguish two radiological patterns of diffuse low-grade gliomas.J Neurooncol. 2017; 133: 37-45
- Apparent diffusion coefficient histograms may predict low-grade glioma subtype.NMR Biomed. 2007; 20: 49-57
- Apparent diffusion coefficient and fractional anisotropy of newly diagnosed grade II gliomas.NMR Biomed. 2009; 22: 449-455
Chaskis C, Stadnik T, Michotte A, Van Rompaey K, D'Haens J. Prognostic value of perfusion-weighted imaging in brain glioma: a prospective study. Acta Neurochir (Wien) 2006;148:277–85; discussion 85.
- Low-grade gliomas: dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging–prediction of patient clinical response.Radiology. 2006; 238: 658-667
- Predicting IDH mutation status in grade II gliomas using amide proton transfer-weighted (APTw) MRI.Magn Reson Med. 2017; 78: 1100-1109
Wenger KJ, Hattingen E, Franz K, Steinbach J, Bahr O, Pilatus U. In vivo metabolic profiles as determined by (31)P and short TE (1)H MR-spectroscopy: no difference between patients with IDH wildtype and IDH mutant gliomas. Clin Neuroradiol 2017.
- Prognostic value of choline and creatine in WHO grade II gliomas.Neuroradiology. 2008; 50: 759-767
- 2-hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data.Neuro Oncol. 2018;
- Prognostic value of O-(2–18F-fluoroethyl)-L-tyrosine PET and MRI in low-grade glioma.J Nucl Med. 2007; 48: 519-527
- The use of dynamic O-(2–18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma.Neuro Oncol. 2015; 17: 1293-1300
- Role of O-(2–18F-fluoroethyl)-L-tyrosine PET as a diagnostic tool for detection of malignant progression in patients with low-grade glioma.J Nucl Med. 2013; 54: 2046-2054
- Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications.Acta Neurochir (Wien). 2018; 160: 1451-1460
- Low-grade gliomas in adults.J Neurosurg. 2011; 115: 948-965
Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al. CBTRUS Statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol 2015;17 Suppl 4:iv1-iv62.
- IDH1 mutation may not be prognostically favorable in glioblastoma when controlled for tumor location: a case-control study.J Clin Neurosci. 2016; 34: 117-120
- Imaging prediction of isocitrate dehydrogenase (IDH) mutation in patients with glioma: a systemic review and meta-analysis.Eur Radiol. 2018;
- Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article.J Neurosurg. 2013; 118: 1157-1168
- Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.Cancer. 2008; 113: 1953-1968
- Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.Epilepsia. 2017; 58: 2038-2047
- IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas.Epilepsia. 2014; 55: 1438-1443
- IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: a systematic review and meta-analysis.Seizure. 2018; 55: 76-82
- Epileptic seizures and survival in early disease of grade 2 gliomas.Eur J Neurol. 2009; 16: 823-831
- Seizure characteristics and control following resection in 332 patients with low-grade gliomas.J Neurosurg. 2008; 108: 227-235
- Tumor-related neurocognitive dysfunction in patients with diffuse glioma: a systematic review of neurocognitive functioning prior to anti-tumor treatment.J Neurooncol. 2017; 134: 9-18
- Prognostic factors for survival in adult patients with cerebral low-grade glioma.J Clin Oncol. 2002; 20: 2076-2084
- No prognostic value of IDH1 mutations in a series of 100 WHO grade II astrocytomas.J Neurooncol. 2012; 109: 15-22
- Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life.Ann Neurol. 2003; 54: 514-520
- Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials.Neuro Oncol. 2017; 19: 12-21
- Natural history and surgical management of incidentally discovered low-grade gliomas.J Neurosurg. 2012; 116: 365-372
- Low-grade gliomas associated with intractable epilepsy: seizure outcome utilizing electrocorticography during tumor resection.J Neurosurg. 1993; 79: 62-69
- Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome.Epilepsia. 1991; 32: 179-186
- Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study.Neuro Oncol. 2012; 14: 230-241
- Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom.Arq Neuropsiquiatr. 2015; 73: 924-928
Tanriverdi T, Kemerdere R, Baran O, Sayyahmelli S, Ozlen F, Isler C, et al. Long-term surgical and seizure outcomes of frontal low-grade gliomas. Int J Surg 2016;33 Pt A:60–4.
- Surgery guided with intraoperative electrocorticography in patients with low-grade glioma and refractory seizures.J Neurosurg. 2018; 128: 840-845
Englot DJ, Han SJ, Berger MS, Barbaro NM, Chang EF. Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors. Neurosurgery. 2012;70:921–8; discussion 8.
- An extent of resection threshold for seizure freedom in patients with low-grade gliomas.J Neurosurg. 2018; 128: 1084-1090
- Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas.JAMA. 2012; 308: 1881-1888
- Surgical resection versus watchful waiting in low-grade gliomas.Ann Oncol. 2017; 28: 1942-1948
- Residual tumor volume as best outcome predictor in low grade glioma - a nine-years near-randomized survey of surgery vs. Biopsy.Sci Rep. 2016; 6: 32286
- The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas.Cancer. 1994; 74: 1784-1791
- Comparative volumetric analysis of the extent of resection of molecularly and histologically distinct low grade gliomas and its role on survival.J Neurooncol. 2017; 134: 65-74
- Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial.Lancet Oncol. 2011; 12: 997-1003
Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, et al. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008;62:564–76; discussion -76.
- Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial.J Neurosurg. 2008; 109: 835-841
- Relationship between the extent of resection and the survival of patients with low-grade gliomas: a systematic review and meta-analysis.BMC Cancer. 2018; 18: 48
- Awake surgery for WHO Grade II gliomas within “noneloquent” areas in the left dominant hemisphere: toward a “supratotal” resection. Clinical article.J Neurosurg. 2011; 115: 232-239
- Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up.Acta Neurochir (Wien). 2016; 158: 51-58
- The error of Broca: From the traditional localizationist concept to a connectomal anatomy of human brain.J Chem Neuroanat. 2018; 89: 73-81
- The rationale to perform early resection in incidental diffuse low-grade glioma: toward a “preventive surgical neurooncology”.World Neurosurg. 2013; 80: e115-e117
- Functional outcome after language mapping for glioma resection.N Engl J Med. 2008; 358: 18-27
- Intraoperative subcortical stimulation mapping for hemispherical perirolandic gliomas located within or adjacent to the descending motor pathways: evaluation of morbidity and assessment of functional outcome in 294 patients.J Neurosurg. 2004; 100: 369-375
- Intra-operative direct electrical stimulations of the central nervous system: the Salpetriere experience with 60 patients.Acta Neurochir (Wien). 1999; 141: 1157-1167
- Cortical and subcortical motor mapping in rolandic and perirolandic glioma surgery: impact on postoperative morbidity and extent of resection.J Neurosurg Sci. 2007; 51: 45-51
- Postoperative deficits and functional recovery following removal of tumors involving the dominant hemisphere supplementary motor area.J Neurosurg. 1991; 75: 62-68
- Proposal of an optimized strategy for intraoperative testing of speech and language during awake mapping.Neurosurg Rev. 2017; 40: 29-35
- Structural and functional integration between dorsal and ventral language streams as revealed by blunt dissection and direct electrical stimulation.Hum Brain Mapp. 2016; 37: 3858-3872
- The course and the anatomo-functional relationships of the optic radiation: a combined study with 'post mortem' dissections and 'in vivo' direct electrical mapping.J Anat. 2015; 226: 47-59
- Electrical stimulation of the dorsolateral prefrontal cortex impairs semantic cognition.Neurology. 2018; 90: e1077-e1084
- Challenging the Myth of Right Nondominant Hemisphere: Lessons from Corticosubcortical Stimulation Mapping in Awake Surgery and Surgical Implications.World Neurosurg. 2017; 103: 449-456
- NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide.J Clin Oncol. 2009; 27: 5874-5880
- Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951.J Clin Oncol. 2013; 31: 344-350
- Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402.J Clin Oncol. 2013; 31: 337-343
- Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH.J Clin Oncol. 2014; 32: 783-790
- Interim results from the CATNON trial (EORTC study 26053–22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study.Lancet. 2017; 390: 1645-1653
- Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.N Engl J Med. 2005; 352: 987-996
- MGMT gene silencing and benefit from temozolomide in glioblastoma.N Engl J Med. 2005; 352: 997-1003
- European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas.Lancet Oncol. 2017; 18: e315-e329
- Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma.N Engl J Med. 2016; 374: 1344-1355
- Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review.Neuro Oncol. 2015; 17: 924-934
- IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas.Neurology. 2010; 75: 1560-1566
- IDH1/2 mutation is a prognostic marker for survival and predicts response to chemotherapy for grade II gliomas concomitantly treated with radiation therapy.Int J Oncol. 2012; 41: 1325-1336
- MGMT methylation: a marker of response to temozolomide in low-grade gliomas.Ann Neurol. 2006; 60: 740-743
- Multiinstitutional validation of the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System. Clinical article.J Neurosurg. 2009; 111: 203-210
- The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma.J Neurooncol. 2017; 135: 535-543
- Influence of blood-brain barrier efflux pumps on the distribution of vincristine in brain and brain tumors.Neuro Onco. 2010; 12: 1043-1049
- Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.Oncotarget. 2018; 9: 33623-33633
- Diffuse infiltrating oligodendroglioma and astrocytoma.J Clin Oncol. 2017; 35: 2394-2401
- A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844.Int J Radiat Oncol Biol Phys. 1996; 36: 549-556
- Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BRO4: an interim analysis.Int J Radiat Oncol Biol Phys. 2002; 52: 316-324
- Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study.J Clin Oncol. 2002; 20: 2267-2276
- Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033–26033): a randomised, open-label, phase 3 intergroup study.Lancet Oncol. 2016; 17: 1521-1532
Article info
Publication history
Published online: May 04, 2020
Accepted:
April 26,
2020
Received:
October 8,
2019
Identification
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Crown Copyright © 2020 Published by Elsevier Ltd. All rights reserved.
