Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Clinical presentation, initial surgical approach, and prognosis of high-grade gliomas

Jorg Dietrich, MD, PhD
Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD
Deputy Editor
April F Eichler, MD, MPH


High-grade gliomas are malignant, often rapidly progressive brain tumors that are divided into anaplastic gliomas (anaplastic astrocytoma, anaplastic oligodendroglioma) and glioblastoma based upon their histopathologic and molecular features. (See "Classification and pathologic diagnosis of gliomas", section on 'Histopathologic and molecular classification'.)

The clinical manifestations, prognostic factors, and initial surgical approach to patients with high-grade gliomas will be reviewed here.

Other patient management topics that are covered separately include:

The diagnostic approach to patients with suspected brain tumors (see "Overview of the clinical features and diagnosis of brain tumors in adults")

Adjuvant radiation therapy and chemotherapy following initial surgery (see "Radiation therapy for high-grade gliomas" and "Initial postoperative therapy for glioblastoma and anaplastic astrocytoma")

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 29, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Chang SM, Parney IF, Huang W, et al. Patterns of care for adults with newly diagnosed malignant glioma. JAMA 2005; 293:557.
  2. Wheen LC, Anderson NE, Baker PC, et al. Leptomeningeal infiltration as the presenting manifestation of a malignant glioma. J Clin Neurosci 2006; 13:298.
  3. Cho TA, Chi AS, Schaefer PW, Louis DN. Case records of the Massachusetts General Hospital. Case 8-2014. A 29-year-old man with headache, vomiting, and diplopia. N Engl J Med 2014; 370:1049.
  4. Wagner S, Benesch M, Berthold F, et al. Secondary dissemination in children with high-grade malignant gliomas and diffuse intrinsic pontine gliomas. Br J Cancer 2006; 95:991.
  5. Narin O, Drappatz J, Doherty LM, et al. Cerebrospinal fluid spread of anaplastic glioma. J Clin Oncol 2007; 25:596.
  6. Scott JN, Brasher PM, Sevick RJ, et al. How often are nonenhancing supratentorial gliomas malignant? A population study. Neurology 2002; 59:947.
  7. Woodworth GF, McGirt MJ, Samdani A, et al. Frameless image-guided stereotactic brain biopsy procedure: diagnostic yield, surgical morbidity, and comparison with the frame-based technique. J Neurosurg 2006; 104:233.
  8. Steinmetz MP, Barnett GH, Kim BS, et al. Metastatic seeding of the stereotactic biopsy tract in glioblastoma multiforme: case report and review of the literature. J Neurooncol 2001; 55:167.
  9. Perrin RG, Bernstein M. Iatrogenic seeding of anaplastic astrocytoma following stereotactic biopsy. J Neurooncol 1998; 36:243.
  10. Pirotte B, Goldman S, Massager N, et al. Comparison of 18F-FDG and 11C-methionine for PET-guided stereotactic brain biopsy of gliomas. J Nucl Med 2004; 45:1293.
  11. McKnight TR, von dem Bussche MH, Vigneron DB, et al. Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg 2002; 97:794.
  12. Hall WA, Liu H, Maxwell RE, Truwit CL. Influence of 1.5-Tesla intraoperative MR imaging on surgical decision making. Acta Neurochir Suppl 2003; 85:29.
  13. Herminghaus S, Dierks T, Pilatus U, et al. Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data. J Neurosurg 2003; 98:74.
  14. Brown TJ, Brennan MC, Li M, et al. Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis. JAMA Oncol 2016; 2:1460.
  15. Trifiletti DM, Alonso C, Grover S, et al. Prognostic Implications of Extent of Resection in Glioblastoma: Analysis from a Large Database. World Neurosurg 2017; 103:330.
  16. Barker FG 2nd, Curry WT Jr, Carter BS. Surgery for primary supratentorial brain tumors in the United States, 1988 to 2000: the effect of provider caseload and centralization of care. Neuro Oncol 2005; 7:49.
  17. Pirotte B, Goldman S, Dewitte O, et al. Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures. J Neurosurg 2006; 104:238.
  18. Krishnan R, Raabe A, Hattingen E, et al. Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome. Neurosurgery 2004; 55:904.
  19. Ganslandt O, Buchfelder M, Hastreiter P, et al. Magnetic source imaging supports clinical decision making in glioma patients. Clin Neurol Neurosurg 2004; 107:20.
  20. Kamada K, Todo T, Masutani Y, et al. Visualization of the frontotemporal language fibers by tractography combined with functional magnetic resonance imaging and magnetoencephalography. J Neurosurg 2007; 106:90.
  21. Hervey-Jumper SL, Li J, Lau D, et al. Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period. J Neurosurg 2015; 123:325.
  22. Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping for glioma resection. N Engl J Med 2008; 358:18.
  23. Kubben PL, ter Meulen KJ, Schijns OE, et al. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol 2011; 12:1062.
  24. Barone DG, Lawrie TA, Hart MG. Image guided surgery for the resection of brain tumours. Cochrane Database Syst Rev 2014; :CD009685.
  25. Senft C, Bink A, Franz K, et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011; 12:997.
  26. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208630s000lbl.pdf.
  27. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006; 7:392.
  28. Pichlmeier U, Bink A, Schackert G, et al. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro Oncol 2008; 10:1025.
  29. Mansouri A, Mansouri S, Hachem LD, et al. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review. Cancer 2016; 122:2469.
  30. Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, Prospective Double-Blinded Study Comparing 3 Different Doses of 5-Aminolevulinic Acid for Fluorescence-Guided Resections of Malignant Gliomas. Neurosurgery 2017; 81:230.
  31. Nickel K, Renovanz M, König J, et al. The patients' view: impact of the extent of resection, intraoperative imaging, and awake surgery on health-related quality of life in high-grade glioma patients-results of a multicenter cross-sectional study. Neurosurg Rev 2017.
  32. Dinapoli RP, Brown LD, Arusell RM, et al. Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma. J Clin Oncol 1993; 11:1316.
  33. Quigley MR, Maroon JC. The relationship between survival and the extent of the resection in patients with supratentorial malignant gliomas. Neurosurgery 1991; 29:385.
  34. Kreth FW, Warnke PC, Scheremet R, Ostertag CB. Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme. J Neurosurg 1993; 78:762.
  35. Sandberg-Wollheim M, Malmström P, Strömblad LG, et al. A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4. Cancer 1991; 68:22.
  36. Devaux BC, O'Fallon JR, Kelly PJ. Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 1993; 78:767.
  37. Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 1993; 26:239.
  38. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001; 95:190.
  39. Bucci MK, Maity A, Janss AJ, et al. Near complete surgical resection predicts a favorable outcome in pediatric patients with nonbrainstem, malignant gliomas: results from a single center in the magnetic resonance imaging era. Cancer 2004; 101:817.
  40. Kreth FW, Thon N, Simon M, et al. Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol 2013; 24:3117.
  41. Noorbakhsh A, Tang JA, Marcus LP, et al. Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg 2014; 120:31.
  42. Sanai N, Mirzadeh Z, Polley M, Berger M. The Value of Glioblastoma Extent of Resection: A Volumetric Analysis of 500 Patients (abstract). Presented at Am Assoc Neuro Surg meeting, 2010.
  43. Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol 2014; 16:113.
  44. Beiko J, Suki D, Hess KR, et al. 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.
  45. WHO Classification of Tumours of the Central Nervous System, 4th ed, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (Eds), IARC, Lyon 2016.
  46. van den Bent MJ, Weller M, Wen PY, et al. A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics. Neuro Oncol 2017; 19:614.
  47. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med 2015; 373:726.
  48. Ostrom QT, Gittleman H, Xu J, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013. Neuro Oncol 2016; 18:v1.
  49. Chien LN, Gittleman H, Ostrom QT, et al. Comparative Brain and Central Nervous System Tumor Incidence and Survival between the United States and Taiwan Based on Population-Based Registry. Front Public Health 2016; 4:151.
  50. Gramatzki D, Dehler S, Rushing EJ, et al. Glioblastoma in the Canton of Zurich, Switzerland revisited: 2005 to 2009. Cancer 2016; 122:2206.
  51. Gittleman H, Lim D, Kattan MW, et al. An independently validated nomogram for individualized estimation of survival among patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825. Neuro Oncol 2017; 19:669.
  52. Molitoris JK, Rao YJ, Patel RA, et al. Multi-institutional external validation of a novel glioblastoma prognostic nomogram incorporating MGMT methylation. J Neurooncol 2017; 134:331.
  53. Li J, Wang M, Won M, et al. Validation and simplification of the Radiation Therapy Oncology Group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 2011; 81:623.
  54. Scott JG, Bauchet L, Fraum TJ, et al. Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older. Cancer 2012; 118:5595.
  55. Zhao H, Wang S, Song C, et al. The prognostic value of MGMT promoter status by pyrosequencing assay for glioblastoma patients' survival: a meta-analysis. World J Surg Oncol 2016; 14:261.
  56. Hegi ME, Liu L, Herman JG, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol 2008; 26:4189.
  57. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352:997.
  58. Brandes AA, Franceschi E, Tosoni A, et al. Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 2009; 115:3512.
  59. Gerstner ER, Yip S, Wang DL, et al. Mgmt methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 2009; 73:1509.
  60. Reifenberger G, Hentschel B, Felsberg J, et al. Predictive impact of MGMT promoter methylation in glioblastoma of the elderly. Int J Cancer 2012; 131:1342.
  61. Brandes AA, Tosoni A, Franceschi E, et al. Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status. J Clin Oncol 2009; 27:1275.
  62. van den Bent MJ, Dubbink HJ, Marie Y, et al. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res 2010; 16:1597.
  63. Wick W, Hartmann C, Engel C, et al. 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.
  64. Weller M, Felsberg J, Hartmann C, et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 2009; 27:5743.
  65. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360:765.
  66. Sanson M, Marie Y, Paris S, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009; 27:4150.
  67. Hartmann C, Hentschel B, Simon M, et al. Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations. Clin Cancer Res 2013; 19:5146.
  68. Reifenberger G, Weber RG, Riehmer V, et al. Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling. Int J Cancer 2014; 135:1822.
  69. Simon M, Hosen I, Gousias K, et al. TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas. Neuro Oncol 2015; 17:45.
  70. Nonoguchi N, Ohta T, Oh JE, et al. TERT promoter mutations in primary and secondary glioblastomas. Acta Neuropathol 2013; 126:931.
  71. Labussière M, Boisselier B, Mokhtari K, et al. Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology 2014; 83:1200.
  72. Reuss DE, Mamatjan Y, Schrimpf D, et al. 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.