The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.
Individual Disclosures for the NCCN Central Nervous System Cancers Panel
LouisDN, PerryA, ReifenbergerG, et al.. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol2016;131:803–820.
LouisDN, PerryA, ReifenbergerG, . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803–820.10.1007/s00401-016-1545-127157931)| false
HouillierC, WangX, KaloshiG, et al.. IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology2010;75:1560–1566.
Cancer Genome Atlas Research Network. BratDJ, VerhaakRG, AldapeKD, et al.. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med2015;372:2481–2498. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26061751.
Cancer Genome Atlas Research Network. BratDJ, VerhaakRG, AldapeKD, . Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481–2498. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26061751.2606175110.1056/NEJMoa1402121)| false
Eckel-PassowJE, LachanceDH, MolinaroAM, et al.. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med2015;372:2499–2508.
Eckel-PassowJE, LachanceDH, MolinaroAM, . Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 2015;372:2499–2508.10.1056/NEJMoa140727926061753)| false
WiestlerB, CapperD, SillM, et al.. Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma. Acta Neuropathol2014;128:561–571.
WiestlerB, CapperD, SillM, . Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma. Acta Neuropathol 2014;128:561–571.10.1007/s00401-014-1315-x25008768)| false
WellerM, WeberRG, WillscherE, et al.. Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol2015;129:679–693.
NittaM, MuragakiY, MaruyamaT, et al.. Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection. Neurosurg Focus2015;38:E7.
BaumertBG, HegiME, van den BentMJ, et al.. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol2016;17:1521–1532.
SansonM, MarieY, ParisS, et al.. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol2009;27:4150–4154.
SahmF, ReussD, KoelscheC, et al.. Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol2014;128:551–559.
SahmF, ReussD, KoelscheC, . Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 2014;128:551–559.2514330110.1007/s00401-014-1326-7)| false
PaiT, EpariS, DesaiS, . Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion. Neurol India 2017;65:113–120.10.4103/0028-3886.198195)| false
NeumannJE, DorostkarMM, KorshunovA, et al.. Distinct histomorphology in molecular subgroups of glioblastomas in young patients. J Neuropathol Exp Neurol2016;75:408–414.
NeumannJE, DorostkarMM, KorshunovA, . Distinct histomorphology in molecular subgroups of glioblastomas in young patients. J Neuropathol Exp Neurol 2016;75:408–414.2697536410.1093/jnen/nlw015)| false
DubbinkHJ, AtmodimedjoPN, KrosJM, et al.. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro-oncol2016;18:388–400.
DubbinkHJ, AtmodimedjoPN, KrosJM, . Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro-oncol 2016;18:388–400.2635492710.1093/neuonc/nov182)| false
LabussièreM, IdbaihA, WangXW, . All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology 2010;74:1886–1890.10.1212/WNL.0b013e3181e1cf3a20427748)| false
HorbinskiC. What do we know about IDH1/2 mutations so far, and how do we use it?Acta Neuropathol 2013;125:621–636.2351237910.1007/s00401-013-1106-9)| false
JiaoY, KillelaPJ, ReitmanZJ, et al.. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget2012;3:709–722.
LeeperHE, CaronAA, DeckerPA, . IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. Oncotarget 2015;6:30295–30305.10.18632/oncotarget.449726210286)| false
ReussDE, SahmF, SchrimpfD, et al.. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol2015;129:133–146.
ReussDE, SahmF, SchrimpfD, . ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 2015;129:133–146.10.1007/s00401-014-1370-325427834)| false
AritaH, NaritaY, FukushimaS, et al.. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol2013;126:267–276.
AritaH, NaritaY, FukushimaS, . Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 2013;126:267–276.10.1007/s00401-013-1141-623764841)| false
KillelaPJ, ReitmanZJ, JiaoY, et al.. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA2013;110:6021–6026.
KillelaPJ, ReitmanZJ, JiaoY, . TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA 2013;110:6021–6026.10.1073/pnas.1303607110)| false
KristensenBW, Priesterbach-AckleyLP, PetersenJK, . Molecular pathology of tumors of the central nervous system. Ann Oncol 2019;30:1265–1278.3112456610.1093/annonc/mdz164)| false
JiangH, CuiY, WangJ, et al.. Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system. Oncotarget2017;8:20354–20361.
JiangH, CuiY, WangJ, . Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system. Oncotarget 2017;8:20354–20361.10.18632/oncotarget.1355527888628)| false
WickW, RothP, HartmannC, et al.. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro-oncol2016;18:1529–1537.
WickW, RothP, HartmannC, . Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro-oncol 2016;18:1529–1537.27370396)| false
CairncrossJG, WangM, JenkinsRB, et al.. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol2014;32:783–790.
CairncrossJG, WangM, JenkinsRB, . Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol 2014;32:783–790.10.1200/JCO.2013.49.372624516018)| false
EverhardS, KaloshiG, CrinièreE, . MGMT methylation: a marker of response to temozolomide in low-grade gliomas. Ann Neurol 2006;60:740–743.10.1002/ana.2104417192931)| false
GorovetsD, KannanK, ShenR, et al.. IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma. Clin Cancer Res2012;18:2490–2501.
GorovetsD, KannanK, ShenR, . IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma. Clin Cancer Res 2012;18:2490–2501.2241531610.1158/1078-0432.CCR-11-2977)| false
WahlM, PhillipsJJ, MolinaroAM, et al.. Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro-oncol2017;19:242–251.
WahlM, PhillipsJJ, MolinaroAM, . Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro-oncol 2017;19:242–251.)| false
AritaH, YamasakiK, MatsushitaY, et al.. A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathol Commun2016;4:79.
PekmezciM, RiceT, MolinaroAM, et al.. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Acta Neuropathol2017;133:1001–1016.
MöllemannM, WolterM, FelsbergJ, et al.. Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer2005;113:379–385.
MöllemannM, WolterM, FelsbergJ, . Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 2005;113:379–385.1545535010.1002/ijc.20575)| false
HegiME, DiserensAC, GorliaT, . MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997–1003.1575801010.1056/NEJMoa043331)| false
HegiME, DiserensAC, GodardS, et al.. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res2004;10:1871–1874.
HegiME, DiserensAC, GodardS, . Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004;10:1871–1874.10.1158/1078-0432.CCR-03-038415041700)| false
BellEH, ZhangP, FisherBJ, et al.. Association of MGMT promoter methylation status with survival outcomes in patients with high-risk glioma treated with radiotherapy and temozolomide: an analysis from the NRG Oncology/RTOG 0424 trial. JAMA Oncol2018;4:1405–1409.
BellEH, ZhangP, FisherBJ, . Association of MGMT promoter methylation status with survival outcomes in patients with high-risk glioma treated with radiotherapy and temozolomide: an analysis from the NRG Oncology/RTOG 0424 trial. JAMA Oncol 2018;4:1405–1409.10.1001/jamaoncol.2018.197729955793)| false
MalmströmA, GrønbergBH, MarosiC, 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. Lancet Oncol2012;13:916–926.
MalmströmA, GrønbergBH, MarosiC, . Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012;13:916–926.2287784810.1016/S1470-2045(12)70265-6)| false
WickW, PlattenM, MeisnerC, et al.. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol2012;13:707–715.
SturmD, WittH, HovestadtV, et al.. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell2012;22:425–437.
SturmD, WittH, HovestadtV, . Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 2012;22:425–437.10.1016/j.ccr.2012.08.02423079654)| false
KorshunovA, CapperD, ReussD, et al.. Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. Acta Neuropathol2016;131:137–146.
KorshunovA, CapperD, ReussD, . Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. Acta Neuropathol 2016;131:137–146.2648247410.1007/s00401-015-1493-1)| false
PenmanCL, FaulknerC, LowisSP, et al.. Current understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol2015;5:54.
PenmanCL, FaulknerC, LowisSP, . Current understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol 2015;5:54.2578524610.3389/fonc.2015.00054)| false
Kleinschmidt-DeMastersBK, AisnerDL, BirksDK, . Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol 2013;37:685–698.2355238510.1097/PAS.0b013e31827f9c5e)| false
ChapmanPB, HauschildA, RobertC, et al..BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med2011;364:2507–2516.
ChapmanPB, HauschildA, RobertC, .BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507–2516.2163980810.1056/NEJMoa1103782)| false
McArthurGA, ChapmanPB, RobertC, et al.. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol2014;15:323–332.
McArthurGA, ChapmanPB, RobertC, . Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014;15:323–332.10.1016/S1470-2045(14)70012-924508103)| false
ChangS, ZhangP, CairncrossJG, et al.. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro-oncol2017;19:252–258.
ChangS, ZhangP, CairncrossJG, . Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro-oncol 2017;19:252–258.27994066)| false
OlarA, WaniKM, Alfaro-MunozKD, et al.. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol2015;129:585–596.
OlarA, WaniKM, Alfaro-MunozKD, . IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 2015;129:585–596.10.1007/s00401-015-1398-z25701198)| false
HegiME, GenbruggeE, GorliaT, et al.. MGMT promoter methylation cutoff with safety margin for selecting glioblastoma patients into trials omitting temozolomide: a pooled analysis of four clinical trials. Clin Cancer Res2019;25:1809–1816.
HegiME, GenbruggeE, GorliaT, . MGMT promoter methylation cutoff with safety margin for selecting glioblastoma patients into trials omitting temozolomide: a pooled analysis of four clinical trials. Clin Cancer Res 2019;25:1809–1816.10.1158/1078-0432.CCR-18-318130514777)| false
OstromQT, GittlemanH, XuJ, et al.. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013. Neuro-oncol2016;18(suppl_5):v1–v75.
OstromQT, GittlemanH, XuJ, . CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013. Neuro-oncol 2016;18(suppl_5):v1–v75.10.1093/neuonc/now20728475809)| false
ChangEF, PottsMB, KelesGE, et al.. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg2008;108:227–235.
ChangEF, PottsMB, KelesGE, . Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 2008;108:227–235.1824091610.3171/JNS/2008/108/2/0227)| false
SchiffD, Van den BentM, VogelbaumMA, et al.. Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro-oncol2019;21:837–853.
SchiffD, Van den BentM, VogelbaumMA, . Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro-oncol 2019;21:837–853.3075357910.1093/neuonc/noz033)| false
PiepmeierJ, ChristopherS, SpencerD, et al.. Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas. Neurosurgery1996;38:872–879.
PiepmeierJ, ChristopherS, SpencerD, . Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas. Neurosurgery 1996;38:872–879.10.1097/00006123-199605000-000028727811)| false
AfraD, OsztieE, SiposL, et al.. Preoperative history and postoperative survival of supratentorial low-grade astrocytomas. Br J Neurosurg1999;13:299–305.
GalloP, CecchiPC, LocatelliF, et al.. Pleomorphic xanthoastrocytoma: long-term results of surgical treatment and analysis of prognostic factors. Br J Neurosurg2013;27:759–764.
GianniniC, ScheithauerBW, BurgerPC, . Pleomorphic xanthoastrocytoma: what do we really know about it?Cancer 1999;85:2033–2045.1022324610.1002/(SICI)1097-0142(19990501)85:9<2033::AID-CNCR22>3.0.CO;2-Z)| false
VarshneyaK, SarmientoJM, NuñoM, . A national perspective of adult gangliogliomas. J Clin Neurosci 2016;30:65–70.2708313310.1016/j.jocn.2015.12.028)| false
Tahiri ElousroutiL, LamchahabM, BougtoubN, et al.. Subependymal giant cell astrocytoma (SEGA): a case report and review of the literature. J Med Case Reports2016;10:35.
Tahiri ElousroutiL, LamchahabM, BougtoubN, . Subependymal giant cell astrocytoma (SEGA): a case report and review of the literature. J Med Case Reports 2016;10:35.10.1186/s13256-016-0818-6)| false
RothJ, RoachES, BartelsU, et al.. Subependymal giant cell astrocytoma: diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol2013;49:439–444.
AdriaensenME, Schaefer-ProkopCM, StijnenT, et al.. Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol2009;16:691–696.
AdriaensenME, Schaefer-ProkopCM, StijnenT, . Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol 2009;16:691–696.10.1111/j.1468-1331.2009.02567.x)| false
SkalickyAM, RentzAM, LiuZ, et al.. The burden of subependymal giant cell astrocytomas associated with tuberous sclerosis complex: results of a patient and caregiver survey. J Child Neurol2015;30:563–569.
SkalickyAM, RentzAM, LiuZ, . The burden of subependymal giant cell astrocytomas associated with tuberous sclerosis complex: results of a patient and caregiver survey. J Child Neurol 2015;30:563–569.2466773810.1177/0883073814523318)| false
SunP, KohrmanM, LiuJ, et al.. Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin2012;28:657–663.
SunP, KohrmanM, LiuJ, . Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin 2012;28:657–663.2237595810.1185/03007995.2012.658907)| false
BerhoumaM, DubourgJ, MessererM. Neurology: Letter to the editor. Re: Sun P, Kohrman M, Liu J et al. Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin 2012;28:657-63. Curr Med Res Opin2012;28:1571–1572., author reply 1572–1573.
BerhoumaM, DubourgJ, MessererM. Neurology: Letter to the editor. Re: Sun P, Kohrman M, Liu J et al. Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin 2012;28:657-63. Curr Med Res Opin 2012;28:1571–1572., author reply 1572–1573.)| false
WenP, SteinA, van den BentM, 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). Neuro-oncol2019;21(Supplement_6):vi19–vi20.
WenP, SteinA, van den BentM, . 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). Neuro-oncol 2019;21(Supplement_6):vi19–vi20.10.1093/neuonc/noz175.073)| false
MarksAM, BindraRS, DiLunaML, et al.. Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatr Blood Cancer2018;65:e26969.
MarksAM, BindraRS, DiLunaML, . Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatr Blood Cancer 2018;65:e26969.10.1002/pbc.26969)| false
FranzDN, BelousovaE, SparaganaS, et al.. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet2013;381:125–132.
FranzDN, BelousovaE, SparaganaS, et al.. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol2014;15:1513–1520.
WahlM, ChangSM, PhillipsJJ, et al.. Probing the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in gliomas: A phase 2 study of everolimus for recurrent adult low-grade gliomas. Cancer2017;123:4631–4639.
WahlM, ChangSM, PhillipsJJ, . Probing the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in gliomas: A phase 2 study of everolimus for recurrent adult low-grade gliomas. Cancer 2017;123:4631–4639.10.1002/cncr.3090928759109)| false
OstromQT, CioffiG, GittlemanH, et al.. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro-oncol2019;21(Suppl 5):v1–v100.
OstromQT, CioffiG, GittlemanH, . CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro-oncol 2019;21(Suppl 5):v1–v100.3167509410.1093/neuonc/noz150)| false
PignattiF, van den BentM, CurranD, et al.. Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol2002;20:2076–2084.
PignattiF, van den BentM, CurranD, . Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 2002;20:2076–2084.1195626810.1200/JCO.2002.08.121)| false
DanielsTB, BrownPD, FeltenSJ, et al.. Validation of EORTC prognostic factors for adults with low-grade glioma: a report using intergroup 86-72-51. Int J Radiat Oncol Biol Phys2011;81:218–224.
DanielsTB, BrownPD, FeltenSJ, . Validation of EORTC prognostic factors for adults with low-grade glioma: a report using intergroup 86-72-51. Int J Radiat Oncol Biol Phys 2011;81:218–224.10.1016/j.ijrobp.2010.05.00321549518)| false
LoSS, ChoKH, HallWA, et al.. Does the extent of surgery have an impact on the survival of patients who receive postoperative radiation therapy for supratentorial low-grade gliomas?Int J Cancer2001; 96(S1, Suppl)71–78.
LoSS, ChoKH, HallWA, . Does the extent of surgery have an impact on the survival of patients who receive postoperative radiation therapy for supratentorial low-grade gliomas?Int J Cancer 2001; 96(S1, Suppl)71–78.1199238810.1002/ijc.10359)| false
ShawE, ArusellR, ScheithauerB, et al.. 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 Oncol2002;20:2267–2276.
ShawE, ArusellR, ScheithauerB, . 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;20:2267–2276.1198099710.1200/JCO.2002.09.126)| false
LoSS, HallWA, ChoKH, et al.. Radiation dose response for supratentorial low-grade glioma--institutional experience and literature review. J Neurol Sci2003;214:43–48.
ShawEG, BerkeyB, CoonsSW, et al.. Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg2008;109:835–841.
JacksonRJ, FullerGN, Abi-SaidD, . Limitations of stereotactic biopsy in the initial management of gliomas. Neuro-oncol 2001;3:193–200.1146540010.1093/neuonc/3.3.193)| false
Villena MartínM, Pena PardoFJ, Jiménez AragónF, et al.. Metabolic targeting can improve the efficiency of brain tumor biopsies. Semin Oncol2020;47:148–154.
BrownTJ, BotaDA, van Den BentMJ, . Management of low-grade glioma: a systematic review and meta-analysis. Neurooncol Pract 2019;6:249–258.31386075)| false
YangK, NathS, KoziarzA, et al.. Biopsy versus subtotal versus gross total resection in patients with low-grade glioma: a systematic review and meta-analysis. World Neurosurg2018;120:e762–e775.
YangK, NathS, KoziarzA, . Biopsy versus subtotal versus gross total resection in patients with low-grade glioma: a systematic review and meta-analysis. World Neurosurg 2018;120:e762–e775.3017297210.1016/j.wneu.2018.08.163)| false
TangS, LiaoJ, LongY. Comparative assessment of the efficacy of gross total versus subtotal total resection in patients with glioma: a meta-analysis. Int J Surg2019;63:90–97.
TangS, LiaoJ, LongY. Comparative assessment of the efficacy of gross total versus subtotal total resection in patients with glioma: a meta-analysis. Int J Surg 2019;63:90–97.3074293410.1016/j.ijsu.2019.02.004)| false
McGirtMJ, ChaichanaKL, AttenelloFJ, et al.. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery2008;63:700–707., author reply 707–708.
JakolaAS, MyrmelKS, KlosterR, et al.. Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA2012;308:1881–1888.
JakolaAS, MyrmelKS, KlosterR, . Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA 2012;308:1881–1888.10.1001/jama.2012.12807)| false
BergerMS, DeliganisAV, DobbinsJ, et al.. The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas. Cancer1994;74:1784–1791.
BergerMS, DeliganisAV, DobbinsJ, . The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas. Cancer 1994;74:1784–1791.808208110.1002/1097-0142(19940915)74:6<1784::AID-CNCR2820740622>3.0.CO;2-D)| false
KiliçT, OzdumanK, ElmaciI, et al.. Effect of surgery on tumor progression and malignant degeneration in hemispheric diffuse low-grade astrocytomas. J Clin Neurosci2002;9:549–552.
KiliçT, OzdumanK, ElmaciI, . Effect of surgery on tumor progression and malignant degeneration in hemispheric diffuse low-grade astrocytomas. J Clin Neurosci 2002;9:549–552.10.1054/jocn.2002.113612383413)| false
RoelzR, StrohmaierD, JabbarliR, et al.. Residual tumor volume as best outcome predictor in low grade glioma - a nine-years near-randomized survey of surgery vs biopsy. Sci Rep2016;6:32286.
RoelzR, StrohmaierD, JabbarliR, . Residual tumor volume as best outcome predictor in low grade glioma - a nine-years near-randomized survey of surgery vs biopsy. Sci Rep 2016;6:32286.2757403610.1038/srep32286)| false
KarimAB, MaatB, HatlevollR, et al.. 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 Phys1996;36:549–556.
KarimAB, MaatB, HatlevollR, . 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;36:549–556.894833810.1016/S0360-3016(96)00352-5)| false
van den BentMJ, AfraD, de WitteO, et al.. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet2005;366:985–990.
van den BentMJ, AfraD, de WitteO, . Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 2005;366:985–990.10.1016/S0140-6736(05)67070-5)| false
GorliaT, WuW, WangM, et al.. New validated prognostic models and prognostic calculators in patients with low-grade gliomas diagnosed by central pathology review: a pooled analysis of EORTC/RTOG/NCCTG phase III clinical trials. Neuro-oncol2013;15:1568–1579.
GorliaT, WuW, WangM, . New validated prognostic models and prognostic calculators in patients with low-grade gliomas diagnosed by central pathology review: a pooled analysis of EORTC/RTOG/NCCTG phase III clinical trials. Neuro-oncol 2013;15:1568–1579.2404911110.1093/neuonc/not117)| false
ShawEG, WangM, CoonsSW, et al.. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol2012;30:3065–3070.
BucknerJC, ShawEG, PughSL, . Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 2016;374:1344–1355.2705020610.1056/NEJMoa1500925)| false
BellEH, ZhangP, ShawEG, et al.. Comprehensive genomic analysis in NRG Oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J Clin Oncol2020;JCO1902983:JCO1902983.
BellEH, ZhangP, ShawEG, . Comprehensive genomic analysis in NRG Oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J Clin Oncol 2020;JCO1902983:JCO1902983.)| false
FisherBJ, HuC, MacdonaldDR, et al.. Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas: preliminary results of Radiation Therapy Oncology Group 0424. Int J Radiat Oncol Biol Phys2015;91:497–504.
NavarriaP, PessinaF, CozziL, et al.. Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy. BMC Cancer2016;16:362.
NavarriaP, PessinaF, CozziL, . Can advanced new radiation therapy technologies improve outcome of high grade glioma (HGG) patients? analysis of 3D-conformal radiotherapy (3DCRT) versus volumetric-modulated arc therapy (VMAT) in patients treated with surgery, concomitant and adjuvant chemo-radiotherapy. BMC Cancer 2016;16:362.27287048)| false
DingM, NewmanF, ChenC, et al.. Dosimetric comparison between 3DCRT and IMRT using different multileaf collimators in the treatment of brain tumors. Med Dosim2009;34:1–8.
DingM, NewmanF, ChenC, . Dosimetric comparison between 3DCRT and IMRT using different multileaf collimators in the treatment of brain tumors. Med Dosim 2009;34:1–8.10.1016/j.meddos.2007.04.00119181248)| false
ShawEG, Daumas-DuportC, ScheithauerBW, et al.. Radiation therapy in the management of low-grade supratentorial astrocytomas. J Neurosurg1989;70:853–861.
IndelicatoDJ, RotondoRL, UezonoH, et al.. Outcomes following proton therapy for pediatric low-grade glioma. Int J Radiat Oncol Biol Phys2019;104:149–156.
NahedBV, RedjalN, BratDJ, et al.. Management of patients with recurrence of diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline. J Neurooncol2015;125:609–630.
NahedBV, RedjalN, BratDJ, . Management of patients with recurrence of diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline. J Neurooncol 2015;125:609–630.10.1007/s11060-015-1910-226530264)| false
SmithJS, ChangEF, LambornKR, et al.. Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol2008;26:1338–1345.
SmithJS, ChangEF, LambornKR, . Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 2008;26:1338–1345.10.1200/JCO.2007.13.933718323558)| false
UppstromTJ, SinghR, HadjigeorgiouGF, et al.. Repeat surgery for recurrent low-grade gliomas should be standard of care. Clin Neurol Neurosurg2016;151:18–23.
UppstromTJ, SinghR, HadjigeorgiouGF, . Repeat surgery for recurrent low-grade gliomas should be standard of care. Clin Neurol Neurosurg 2016;151:18–23.10.1016/j.clineuro.2016.09.01327736650)| false
KesariS, SchiffD, DrappatzJ, . Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res 2009;15:330–337.10.1158/1078-0432.CCR-08-088819118062)| false
NicholsonHS, KretschmarCS, KrailoM, et al.. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer2007;110:1542–1550.
NicholsonHS, KretschmarCS, KrailoM, . Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 2007;110:1542–1550.1770517510.1002/cncr.22961)| false
MoghrabiA, FriedmanHS, AshleyDM, . Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurg Focus 1998;4:e3.10.3171/foc.1998.4.4.617168503)| false
BrandesAA, BassoU, VastolaF, et al.. Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol2003;14:1727–1731.
BrandesAA, BassoU, VastolaF, . Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol 2003;14:1727–1731.1463067610.1093/annonc/mdg494)| false
van den BentMJ, BaumertB, ErridgeSC, et al.. 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. Lancet2017;390:1645–1653.
van den BentMJ, BaumertB, ErridgeSC, . 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;390:1645–1653.10.1016/S0140-6736(17)31442-3)| false
PerryJR, LaperriereN, O’CallaghanCJ, et al.. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med2017;376:1027–1037.
PerryJR, LaperriereN, O’CallaghanCJ, . Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 2017;376:1027–1037.10.1056/NEJMoa161197728296618)| false
StuppR, MasonWP, van den BentMJ, . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.10.1056/NEJMoa04333015758009)| false
AcharyaS, RobinsonCG, MichalskiJM, et al.. Association of 1p/19q codeletion and radiation necrosis in adult cranial gliomas after proton or photon therapy. Int J Radiat Oncol Biol Phys2018;101:334–343.
AcharyaS, RobinsonCG, MichalskiJM, . Association of 1p/19q codeletion and radiation necrosis in adult cranial gliomas after proton or photon therapy. Int J Radiat Oncol Biol Phys 2018;101:334–343.10.1016/j.ijrobp.2018.01.09929534896)| false
WenPY, WellerM, LeeEQ, et al.. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol 2020. Accessed August 26, 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32328653
122.
ArevaloOD, SotoC, RabieiP, et al.. Assessment of glioblastoma response in the era of bevacizumab: longstanding and emergent challenges in the imaging evaluation of pseudoresponse. Front Neurol2019;10:460.
ArevaloOD, SotoC, RabieiP, . Assessment of glioblastoma response in the era of bevacizumab: longstanding and emergent challenges in the imaging evaluation of pseudoresponse. Front Neurol 2019;10:460.10.3389/fneur.2019.0046031133966)| false
LiXZ, LiYB, CaoY, et al.. Prognostic implications of resection extent for patients with glioblastoma multiforme: a meta-analysis. J Neurosurg Sci2017;61:631–639.
BeikoJ, SukiD, HessKR, et al.. IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro-oncol2014;16:81–91.
BeikoJ, SukiD, HessKR, . IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro-oncol 2014;16:81–91.10.1093/neuonc/not15924305719)| false
MolinaroAM, Hervey-JumperS, MorshedRA, et al.. Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol2020;6:495–503.
MolinaroAM, Hervey-JumperS, MorshedRA, . Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol 2020;6:495–503.10.1001/jamaoncol.2019.614332027343)| false
BarkerFGII, ChangSM, GutinPH, et al.. Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery1998;42:709–720., discussion 720–723.
BarkerFGII, ChangSM, GutinPH, . Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery 1998;42:709–720., discussion 720–723.10.1097/00006123-199804000-000139574634)| false
ParkJK, HodgesT, ArkoL, . Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 2010;28:3838–3843.2064408510.1200/JCO.2010.30.0582)| false
KristiansenK, HagenS, KollevoldT, et al.. Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer1981;47:649–652.
KristiansenK, HagenS, KollevoldT, . Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 1981;47:649–652.)| false
WalkerMD, AlexanderE, Jr., HuntWE, et al.. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg1978;49:333–343.
WalkerMD, AlexanderE, Jr., HuntWE, . Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978;49:333–343.35560410.3171/jns.1978.49.3.0333)| false
CabreraAR, KirkpatrickJP, FiveashJB, et al.. Radiation therapy for glioblastoma: executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. Pract Radiat Oncol2016;6:217–225.
CabreraAR, KirkpatrickJP, FiveashJB, . Radiation therapy for glioblastoma: executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. Pract Radiat Oncol 2016;6:217–225.10.1016/j.prro.2016.03.00727211230)| false
RoaW, BrasherPM, BaumanG, et al.. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol2004;22:1583–1588.
RoaW, KepkaL, KumarN, et al.. International Atomic Energy Agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol2015;33:4145–4150.
RoaW, KepkaL, KumarN, . International Atomic Energy Agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 2015;33:4145–4150.10.1200/JCO.2015.62.660626392096)| false
KimH, LeibyBE, ShiW. Too little, too soon: short-course radiotherapy in elderly patients with glioblastoma. J Clin Oncol 2016;34:2191–2192.10.1200/JCO.2015.66.319527069070)| false
StuppR, HegiME, MasonWP, 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. Lancet Oncol2009;10:459–466.
StuppR, HegiME, MasonWP, .. 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. Lancet Oncol 2009;10:459–466.10.1016/S1470-2045(09)70025-7)| false
van den BentMJ, CarpentierAF, BrandesAA, et al.. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol2006;24:2715–2722.
van den BentMJ, CarpentierAF, BrandesAA, . Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 2006;24:2715–2722.)| false
van den BentMJ, BrandesAA, TaphoornMJ, et al.. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol2013;31:344–350.
van den BentMJ, BrandesAA, TaphoornMJ, . 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;31:344–350.10.1200/JCO.2012.43.2229)| false
CairncrossG, BerkeyB, ShawE, et al.. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol2006;24:2707–2714.
CairncrossG, BerkeyB, ShawE, . Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 2006;24:2707–2714.1678291010.1200/JCO.2005.04.3414)| false
CairncrossG, WangM, ShawE, et al.. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol2013;31:337–343.
JaeckleKA, BallmanKV, van den BentM, et al.. CODEL: phase III study of RT, RT + temozolomide (TMZ), or TMZ for newly-diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design. Neuro Oncol Accessed August 26, 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32678879
JaeckleKA, BallmanKV, van den BentM, . CODEL: phase III study of RT, RT + temozolomide (TMZ), or TMZ for newly-diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design. Neuro Oncol Accessed August 26, 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3267887910.1093/neuonc/noaa168)| false
van den BentMJ, ErridgeSC, VogelbaumMA, et al.. Second interim and first molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion. ASCO 2019. Accessed August 26, 2020. Available at: https://meetinglibrary.asco.org/record/173361/abstract
142.
ClarkeJL, IwamotoFM, SulJ, et al.. Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J Clin Oncol2009;27:3861–3867.
ClarkeJL, IwamotoFM, SulJ, . Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J Clin Oncol 2009;27:3861–3867.10.1200/JCO.2008.20.794419506159)| false
GilbertMR, WangM, AldapeKD, et al.. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol2013;31:4085–4091.
StuppR, HegiME, GorliaT, 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. Lancet Oncol2014;15:1100–1108.
NaborsLB, FinkKL, MikkelsenT, et al.. Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study. Neuro-oncol2015;17:708–717.
NaborsLB, FinkKL, MikkelsenT, . Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study. Neuro-oncol 2015;17:708–717.10.1093/neuonc/nou35625762461)| false
BlumenthalDT, GorliaT, GilbertMR, et al.. Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro-oncol2017;19:1119–1126.
BlumenthalDT, GorliaT, GilbertMR, . Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG. Neuro-oncol 2017;19:1119–1126.10.1093/neuonc/nox02528371907)| false
BalanaC, VazMA, SepulvedaJM, et al.. A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond six cycles in patients with glioblastoma (GEINO 14-01) [published online April 24, 2020]. Neuro Oncol, doi: 10.1093/neuonc/noaa107 https://www.ncbi.nlm.nih.gov/pubmed/32328662
BalanaC, VazMA, SepulvedaJM, . A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond six cycles in patients with glioblastoma (GEINO 14-01) [published online April 24, 2020]. Neuro Oncol, doi: 10.1093/neuonc/noaa107 https://www.ncbi.nlm.nih.gov/pubmed/32328662)| false
GlasM, HappoldC, RiegerJ, et al.. Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. J Clin Oncol2009;27:1257–1261.
GlasM, HappoldC, RiegerJ, . Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide. J Clin Oncol 2009;27:1257–1261.10.1200/JCO.2008.19.219519188676)| false
HerrlingerU, RiegerJ, KochD, et al.. Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol2006;24:4412–4417.
HerrlingerU, RiegerJ, KochD, . Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. J Clin Oncol 2006;24:4412–4417.10.1200/JCO.2006.06.910416983109)| false
HerrlingerU, TzaridisT, MackF, 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. Lancet2019;393:678–688.
WellerJ, TzaridisT, MackF, et al.. Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol2019;20:1444–1453.
WellerJ, TzaridisT, MackF, . Health-related quality of life and neurocognitive functioning with lomustine-temozolomide versus temozolomide in patients with newly diagnosed, MGMT-methylated glioblastoma (CeTeG/NOA-09): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol 2019;20:1444–1453.3148836010.1016/S1470-2045(19)30502-9)| false
StuppR, TaillibertS, KannerAA, et al.. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA2015;314:2535–2543.
StuppR, TaillibertS, KannerAA, . Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 2015;314:2535–2543.2667097110.1001/jama.2015.16669)| false
StuppR, TaillibertS, KannerA, et al.. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA2017;318:2306–2316.
StuppR, TaillibertS, KannerA, . Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 2017;318:2306–2316.2926022510.1001/jama.2017.18718)| false
TaphoornMJB, DirvenL, KannerAA, et al.. Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial. JAMA Oncol2018;4:495–504.
TaphoornMJB, DirvenL, KannerAA, . Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: a secondary analysis of a randomized clinical trial. JAMA Oncol 2018;4:495–504.10.1001/jamaoncol.2017.508229392280)| false
PerryJR, RizekP, CashmanR, et al.. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the “rescue” approach. Cancer2008;113:2152–2157.
PerryJR, RizekP, CashmanR, . Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the “rescue” approach. Cancer 2008;113:2152–2157.10.1002/cncr.2381318756530)| false
BrandesAA, TosoniA, AmistàP, . How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology 2004;63:1281–1284.10.1212/01.WNL.0000140495.33615.CA)| false
WickW, PuduvalliVK, ChamberlainMC, et al.. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol2010;28:1168–1174.
WickW, PuduvalliVK, ChamberlainMC, . Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 2010;28:1168–1174.10.1200/JCO.2009.23.259520124186)| false
TaalW, OosterkampHM, WalenkampAM, 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. Lancet Oncol2014;15:943–953.
TaalW, OosterkampHM, WalenkampAM, . 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. Lancet Oncol 2014;15:943–953.10.1016/S1470-2045(14)70314-6)| false
FriedmanHS, PradosMD, WenPY, . Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733–4740.1972092710.1200/JCO.2008.19.8721)| false
WickW, GorliaT, BendszusM, . Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 2017;377:1954–1963.10.1056/NEJMoa170735829141164)| false
WickW, WellerM, van den BentM, et al.. Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol2010;28:e188–e189., author reply e190–e192.
WickW, WellerM, van den BentM, . Bevacizumab and recurrent malignant gliomas: a European perspective. J Clin Oncol 2010;28:e188–e189., author reply e190–e192.10.1200/JCO.2009.26.902720159801)| false
LombardiG, De SalvoGL, BrandesAA, et al.. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol2019;20:110–119.
BremH, PiantadosiS, BurgerPC, et al.. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet1995;345:1008–1012.
BremH, PiantadosiS, BurgerPC, . Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 1995;345:1008–1012.10.1016/S0140-6736(95)90755-67723496)| false
McGirtMJ, BremH. Carmustine wafers (Gliadel) plus concomitant temozolomide therapy after resection of malignant astrocytoma: growing evidence for safety and efficacy. Ann Surg Oncol2010;17:1729–1731.
McGirtMJ, BremH. Carmustine wafers (Gliadel) plus concomitant temozolomide therapy after resection of malignant astrocytoma: growing evidence for safety and efficacy. Ann Surg Oncol 2010;17:1729–1731.10.1245/s10434-010-1092-220422453)| false
StuppR, WongET, KannerAA, et al.. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer2012;48:2192–2202.
StuppR, WongET, KannerAA, . NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 2012;48:2192–2202.2260826210.1016/j.ejca.2012.04.011)| false
MohammadiAM, SullivanTB, BarnettGH, et al.. Use of high-field intraoperative magnetic resonance imaging to enhance the extent of resection of enhancing and nonenhancing gliomas. Neurosurgery2014;74:339–348.
MohammadiAM, SullivanTB, BarnettGH, . Use of high-field intraoperative magnetic resonance imaging to enhance the extent of resection of enhancing and nonenhancing gliomas. Neurosurgery 2014;74:339–348.10.1227/NEU.000000000000027824368543)| false
CoburgerJ, WirtzCR. Fluorescence guided surgery by 5-ALA and intraoperative MRI in high grade glioma: a systematic review. J Neurooncol2019;141:533–546.
CoburgerJ, WirtzCR. Fluorescence guided surgery by 5-ALA and intraoperative MRI in high grade glioma: a systematic review. J Neurooncol 2019;141:533–546.3048829310.1007/s11060-018-03052-4)| false
LevinVA, SilverP, HanniganJ, et al.. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys1990;18:321–324.
LevinVA, SilverP, HanniganJ, . Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 1990;18:321–324.215441810.1016/0360-3016(90)90096-3)| false
MinnitiG, ScaringiC, LanzettaG, et al.. Standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol Biol Phys2015;91:109–115.
MinnitiG, ScaringiC, LanzettaG, . Standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol Biol Phys 2015;91:109–115.2544233910.1016/j.ijrobp.2014.09.013)| false
BrandesAA, FranceschiE, TosoniA, et al.. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol2008;26:2192–2197.
BrandesAA, FranceschiE, TosoniA, . MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 2008;26:2192–2197.1844584410.1200/JCO.2007.14.8163)| false
EllingsonBM, ChungC, PopeWB, et al.. Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape. J Neurooncol2017;134:495–504.
TsienC, GalbánCJ, ChenevertTL, et al.. Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma. J Clin Oncol2010;28:2293–2299.
TsienC, GalbánCJ, ChenevertTL, . Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma. J Clin Oncol 2010;28:2293–2299.2036856410.1200/JCO.2009.25.3971)| false
WellerM, TabatabaiG, KästnerB, et al.. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res2015;21:2057–2064.
WellerM, TabatabaiG, KästnerB, . MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res 2015;21:2057–2064.10.1158/1078-0432.CCR-14-273725655102)| false
YungWK, AlbrightRE, OlsonJ, et al.. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer2000;83:588–593.
YungWK, AlbrightRE, OlsonJ, . A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 2000;83:588–593.1094459710.1054/bjoc.2000.1316)| false
PradosM, RodriguezL, ChamberlainM, et al.. Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. Neurosurgery1989;24:806–809.
PradosM, RodriguezL, ChamberlainM, . Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. Neurosurgery 1989;24:806–809.254609310.1227/00006123-198906000-00003)| false
NordenAD, YoungGS, SetayeshK, et al.. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology2008;70:779–787.
CloughesyT, PradosMD, MikkelsenT. A phase 2 randomized non-comparative clinical trial of the effect of bevacizumab alone or in combination with irinotecan on 6-month progression free survival in recurrent refractory glioblastoma. [abstract]J Clin Oncol2008;26(Suppl 15):2010b.
CloughesyT, PradosMD, MikkelsenT. A phase 2 randomized non-comparative clinical trial of the effect of bevacizumab alone or in combination with irinotecan on 6-month progression free survival in recurrent refractory glioblastoma. [abstract]J Clin Oncol 2008;26(Suppl 15):2010b.10.1200/jco.2008.26.15_suppl.2010b)| false
KreislTN, KimL, MooreK, et al.. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol2009;27:740–745.
KreislTN, KimL, MooreK, . Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27:740–745.10.1200/JCO.2008.16.305519114704)| false
VredenburghJJ, DesjardinsA, HerndonJEII, et al.. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res2007;13:1253–1259.
VredenburghJJ, DesjardinsA, HerndonJEII, . Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 2007;13:1253–1259.10.1158/1078-0432.CCR-06-230917317837)| false
Barnholtz-SloanJS, SloanAE, DavisFG, et al.. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol2004;22:2865–2872.
Barnholtz-SloanJS, SloanAE, DavisFG, . Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004;22:2865–2872.1525405410.1200/JCO.2004.12.149)| false
SchoutenLJ, RuttenJ, HuveneersHA, et al.. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer2002;94:2698–2705.
SchoutenLJ, RuttenJ, HuveneersHA, . Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 2002;94:2698–2705.10.1002/cncr.10541)| false
MaherEA, MietzJ, ArteagaCL, . Brain metastasis: opportunities in basic and translational research. Cancer Res 2009;69:6015–6020.1963859310.1158/0008-5472.CAN-08-4347)| false
ChurillaTM, ChowdhuryIH, HandorfE, et al.. Comparison of local control of brain metastases with stereotactic radiosurgery vs surgical resection: a secondary analysis of a randomized clinical trial. JAMA Oncol2019;5:243–247. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30419088.
ChurillaTM, ChowdhuryIH, HandorfE, . Comparison of local control of brain metastases with stereotactic radiosurgery vs surgical resection: a secondary analysis of a randomized clinical trial. JAMA Oncol 2019;5:243–247. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30419088.10.1001/jamaoncol.2018.461030419088)| false
EwendMG, MorrisDE, CareyLA, et al.. Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy. J Natl Compr Canc Netw2008;6:505–513., quiz 514.
EwendMG, MorrisDE, CareyLA, . Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy. J Natl Compr Canc Netw 2008;6:505–513., quiz 514.10.6004/jnccn.2008.003818492462)| false
PatchellRA, TibbsPA, WalshJW, . A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494–500.10.1056/NEJM1990022232208022405271)| false
VechtCJ, Haaxma-ReicheH, NoordijkEM, et al.. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?Ann Neurol1993;33:583–590.
VechtCJ, Haaxma-ReicheH, NoordijkEM, . Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?Ann Neurol 1993;33:583–590.10.1002/ana.4103306058498838)| false
MintzAH, KestleJ, RathboneMP, et al.. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer1996;78:1470–1476.
MintzAH, KestleJ, RathboneMP, . A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996;78:1470–1476.10.1002/(SICI)1097-0142(19961001)78:7<1470::AID-CNCR14>3.0.CO;2-X8839553)| false
AoyamaH, ShiratoH, TagoM, et al.. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA2006;295:2483–2491.
BrownPD, JaeckleK, BallmanKV, et al.. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA2016;316:401–409.
BrownPD, JaeckleK, BallmanKV, . Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 2016;316:401–409.2745894510.1001/jama.2016.9839)| false
ChangEL, WefelJS, HessKR, et al.. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol2009;10:1037–1044.
ChangEL, WefelJS, HessKR, . Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 2009;10:1037–1044.1980120110.1016/S1470-2045(09)70263-3)| false
KocherM, SoffiettiR, AbaciogluU, et al.. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol2011;29:134–141.
KocherM, SoffiettiR, AbaciogluU, . Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 2011;29:134–141.2104171010.1200/JCO.2010.30.1655)| false
