NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

[1]  T. Batchelor,et al.  Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system , 2021, Cancer.

[2]  G. Reifenberger,et al.  The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. , 2021, Neuro-oncology.

[3]  V. Puduvalli,et al.  False-positive 1p/19q Testing Results in Gliomas , 2020, American journal of clinical oncology.

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

[5]  C. Ida,et al.  Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas , 2020, Neuro-oncology advances.

[6]  Wei-wei Wang,et al.  IDH mutant lower grade (WHO Grades II/III) astrocytomas can be stratified for risk by CDKN2A, CDK4 and PDGFRA copy number alterations , 2019, Brain pathology.

[7]  F. Ducray,et al.  PL1.1 CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDHmutant gliomas , 2019, Neuro-Oncology.

[8]  P. Wesseling,et al.  Molecular pathology of tumors of the central nervous system , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  E. Holland,et al.  Targeted copy number analysis outperforms histologic grading in predicting patient survival for WHO grades II/III IDH-mutant astrocytomas. , 2019, Neuro-oncology.

[10]  C. Bettegowda,et al.  Incidence and clinicopathologic features of H3 K27M mutations in adults with radiographically-determined midline gliomas , 2019, Journal of Neuro-Oncology.

[11]  G. Tabatabai,et al.  High frequency of H3 K27M mutations in adult midline gliomas , 2019, Journal of Cancer Research and Clinical Oncology.

[12]  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.

[13]  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.

[14]  K. Aldape,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 , 2018, JAMA oncology.

[15]  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.

[16]  Pieter Wesseling,et al.  cIMPACT-NOW update 2: diagnostic clarifications for diffuse midline glioma, H3 K27M-mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant , 2018, Acta Neuropathologica.

[17]  Kun Mu,et al.  Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma , 2017, Cancer cell.

[18]  F. Ducray,et al.  Characteristics of H3 K27M-mutant gliomas in adults , 2017, Neuro-oncology.

[19]  Jennie W. Taylor,et al.  Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT , 2017, Acta Neuropathologica.

[20]  T. Gupta,et al.  Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion , 2017, Neurology India.

[21]  Susan M. Chang,et al.  Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813 , 2016, Neuro-oncology.

[22]  Yong Cui,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 , 2016, Oncotarget.

[23]  Susan M. Chang,et al.  Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide , 2016, Neuro-oncology.

[24]  Brigitta G. Baumert,et al.  Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma , 2016, The Lancet. Oncology.

[25]  Uri Tabori,et al.  Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma , 2016, Acta Neuropathologica Communications.

[26]  E. Miyaoka,et al.  A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas , 2016, Acta neuropathologica communications.

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

[28]  U. Schüller,et al.  Distinct Histomorphology in Molecular Subgroups of Glioblastomas in Young Patients , 2016, Journal of neuropathology and experimental neurology.

[29]  Pieter Wesseling,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. , 2016, Neuro-oncology.

[30]  G. Reifenberger,et al.  Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. , 2015, Neuro-oncology.

[31]  P. Decker,et al.  IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas , 2015, Oncotarget.

[32]  Steven J. M. Jones,et al.  Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. , 2015, The New England journal of medicine.

[33]  Alexander R. Pico,et al.  Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. , 2015, The New England journal of medicine.

[34]  Arie Perry,et al.  CDKN2A Loss Is Associated With Shortened Overall Survival in Lower-Grade (World Health Organization Grades II–III) Astrocytomas , 2015, Journal of neuropathology and experimental neurology.

[35]  D. Merico,et al.  BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  Gabriele Schackert,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 , 2015, Acta Neuropathologica.

[37]  K. Kurian,et al.  Current Understanding of BRAF Alterations in Diagnosis, Prognosis, and Therapeutic Targeting in Pediatric Low-Grade Gliomas , 2015, Front. Oncol..

[38]  K. Aldape,et al.  IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas , 2015, Acta Neuropathologica.

[39]  Hiroshi Iseki,et al.  Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection. , 2015, Neurosurgical focus.

[40]  Volker Hovestadt,et al.  Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity , 2015, Acta Neuropathologica.

[41]  K. Ligon,et al.  Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas , 2014, Acta Neuropathologica.

[42]  David T. W. Jones,et al.  Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma , 2014, Acta Neuropathologica.

[43]  Martin Sill,et al.  Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma , 2014, Acta Neuropathologica.

[44]  Caterina Giannini,et al.  Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Michael Brudno,et al.  Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations , 2014, Nature Genetics.

[46]  Dirk Schadendorf,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. , 2014, The Lancet. Oncology.

[47]  David T. W. Jones,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 , 2014, Acta Neuropathologica.

[48]  M. Nikiforova,et al.  1p/19q testing has no significance in the workup of glioblastomas , 2013, Neuropathology and applied neurobiology.

[49]  K. Ichimura,et al.  Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss , 2013, Acta Neuropathologica.

[50]  D. Aisner,et al.  Epithelioid GBMs Show a High Percentage of BRAF V600E Mutation , 2013, The American journal of surgical pathology.

[51]  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.

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

[53]  C. Horbinski.  To BRAF or Not to BRAF: Is That Even a Question Anymore? , 2013, Journal of neuropathology and experimental neurology.

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

[55]  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.

[56]  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.

[57]  R. McLendon,et al.  Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas , 2012, Oncotarget.

[58]  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.

[59]  David T. W. Jones,et al.  K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas , 2012, Acta Neuropathologica.

[60]  I. Pollack,et al.  Interplay among BRAF, p16, p53, and MIB1 in pediatric low-grade gliomas. , 2012, Neuro-oncology.

[61]  J. Huse,et al.  IDH Mutation and Neuroglial Developmental Features Define Clinically Distinct Subclasses of Lower Grade Diffuse Astrocytic Glioma , 2012, Clinical Cancer Research.

[62]  A. Hauschild,et al.  Improved survival with vemurafenib in melanoma with BRAF V600E mutation. , 2011, The New England journal of medicine.

[63]  N. Alon,et al.  BRAF-KIAA1549 Fusion Predicts Better Clinical Outcome in Pediatric Low-Grade Astrocytoma , 2011, Clinical Cancer Research.

[64]  R. Guillevin,et al.  IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas , 2010, Neurology.

[65]  K. Hoang-Xuan,et al.  All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2 , 2010, Neurology.

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

[67]  K. Hoang-Xuan,et al.  Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  I. Pollack,et al.  Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas , 2009, Acta Neuropathologica.

[69]  M. Delorenzi,et al.  Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. , 2008, The Journal of molecular diagnostics : JMD.

[70]  K. Hoang-Xuan,et al.  MGMT methylation: A marker of response to temozolomide in low‐grade gliomas , 2006, Annals of neurology.

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

[72]  M. Wolter,et al.  Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors , 2005, International journal of cancer.

[73]  Luca Regli,et al.  Clinical Trial Substantiates the Predictive Value of O-6-Methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastoma Patients Treated with Temozolomide , 2004, Clinical Cancer Research.