Skip to main content

Radiation Therapy in High-Grade Gliomas

  • Living reference work entry
  • First Online:
Radiation Oncology

Abstract

High grade gliomas (HGG) account for the majority of primary malignant brain tumors in adults with increasing incidence in age, peaking in the 75–84 age group. Glioblastoma (GB) is the most frequently occurring subtype, followed by anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA). Since 2016 a new WHO classification has radically changed our understanding of gliomas and introduced a molecular classification system allowing for future, more personalized, treatment approaches.

As the incidence of HGG increases with advancing age, selection of optimal treatment is complicated by preexisting comorbidities and deteriorating performance status. HGG are aggressive tumors which are best managed with a combined modality approach. Maximal surgical resection is associated with improved survival and favorable neurological improved outcome. However, due to the infiltrative nature of HGG, a complete microscopic clearance is rarely possible.

Radiotherapy post surgery  has been the mainstay of treatment for HGG for several decades. Involved field radiotherapy is now the standard approach used to maximize coverage of infiltrative tumor cells, while limiting the volume of normal brain tissue irradiated. Dose escalation above 60Gy, hypo- or hyper-fractionation has not shown any additional benefit. The introduction of concomitant and adjuvant temozolomide to radical radiotherapy has provided a modest but significant improvement in overall survival for patients with GB.

Despite optimal treatment, the prognosis for HGG remains poor with limited treatment options at recurrence. Additional molecular pathways identified in the development of HGG are now the target for novel therapies, which may potentially improve the prognosis of what remains to be a challenging and highly fatal disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Armstrong GT, Jain N, Liu W, Merchant TE, Stovall M, Srivastava DK, Gurney JG, Packer RJ, Robison LL, Krull KR. Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies. Neuro-Oncology. 2010;12(11):1173–86.

    Article  PubMed  PubMed Central  Google Scholar 

  • Avril T, Saikali S, Vauléon E, Jary A, Hamlat A, De Tayrac M, Mosser J, Quillien V. Distinct effects of human glioblastoma immunoregulatory molecules programmed cell death ligand-1 (PDL-1) and indoleamine 2, 3-dioxygenase (IDO) on tumour-specific T cell functions. J Neuroimmunol. 2010;225(1):22–33.

    Article  CAS  PubMed  Google Scholar 

  • Belozerov VE, Van Meir EG. Inhibitors of hypoxia-inducible factor-1 signaling. Curr Opin Investig Drugs. 2006;7:1067–76.

    PubMed  CAS  Google Scholar 

  • Bhandare N, Jackson A, Eisbruch A, et al. Radiation therapy and hearing loss. Int J Radiat Oncol Biol Phys. 2010;76:S50–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bokstein F, Shpigel S, Blumenthal DT. Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors. Cancer. 2008;112(10):2267–73.

    Article  CAS  PubMed  Google Scholar 

  • Brandes AA, Franceschi E, Tosoni A, Hegi ME, Stupp R. Epidermal growth factor receptor inhibitors in neuro-oncology: hopes and disappointments. Clin Cancer Res. 2008;14(4):957–60.

    Article  CAS  PubMed  Google Scholar 

  • Brandsma D, Stalpers L, Taal W, et al. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 2008;9:453–61.

    Article  PubMed  Google Scholar 

  • Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, Muller P. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet. 1995;345(8956):1008–12.

    Article  CAS  PubMed  Google Scholar 

  • Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337.

    Article  CAS  PubMed  Google Scholar 

  • Chamberlain MC. Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol. 2011;5:117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chemaitilly W, Li Z, Huang S, Ness KK, Clark KL, Green DM, Barnes N, Armstrong GT, Krasin MJ, Srivastava DK, Pui CH. Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude lifetime cohort study. J Clin Oncol. 2015;33(5):492–500.

    Article  PubMed  PubMed Central  Google Scholar 

  • Desjardins A, Reardon DA, Herndon JE, Marcello J, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Bailey L, Bigner DD. Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res. 2008;14(21):7068–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dixit S, Hingorani M, Achawal S, Scott I. Retrospective comparison of chemoradiotherapy followed by adjuvant chemotherapy, with or without previous gliadel implantation (carmustine) after initial surgery in patients with newly diagnosed high-grade gliomas: in regard to noel et al. Int J Radiat Oncol Biol Phys. 2011;81(5):1593.

    Article  PubMed  Google Scholar 

  • Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-Oncology. 2012;14(5):v1–49.

    Article  PubMed  PubMed Central  Google Scholar 

  • Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes. Neurol Clin. 2007;25(4):925–46.

    Article  PubMed  Google Scholar 

  • Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin. 2007;25:8678–90.

    Article  Google Scholar 

  • Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007;21:2683–710.

    Article  CAS  PubMed  Google Scholar 

  • Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;31:4085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gondi V, Tolakanahalli R, Mehta MP, Tewatia D, Rowley H, Kuo JS, Khuntia D, Tomé WA. Hippocampal-sparing whole-brain radiotherapy: a “how-to” technique using helical tomotherapy and linear accelerator–based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(4):1244–52.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gorlia T, Stupp R, Brandes AA, et al. New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC brain tumour group phase I and II clinical trials. Eur J Cancer. 2012;48:1176–84.

    Article  PubMed  Google Scholar 

  • Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, Vogelbaum MA. Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg. 2014;121(5):1115–23.

    Article  PubMed  Google Scholar 

  • Hardesty DA, Sanai N. The value of glioma extent of resection in the modern neurosurgical era. Front Neurol. 2012;3:140.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol. 2009;118(4):469–74.

    Article  PubMed  Google Scholar 

  • Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Ronning P, Scheie D, Vik A, Meling TR. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand. 2010;122:159–67.

    Article  CAS  PubMed  Google Scholar 

  • Herrlinger U, Felsberg J, Küker W, et al. Gliomatosis cerebri: molecular pathology and clinical course. Ann Neurol. 2002;52:390–9.

    Article  CAS  PubMed  Google Scholar 

  • Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology. 1980;30(9):907.

    Article  CAS  PubMed  Google Scholar 

  • Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN. Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol. 2009;68(12):1319–25.

    Article  CAS  PubMed  Google Scholar 

  • Hottinger AF, Levivier M, Negretti L, et al. PET imaging in glioma. The neurooncologist’s expectations. PET Clin. 2013;8:117–28.

    Article  PubMed  Google Scholar 

  • Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG. A t (1; 19)(q10; p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res. 2006;66(20):9852–61.

    Article  CAS  PubMed  Google Scholar 

  • Kleinschmidt-DeMasters BK, Aisner DL, Birks DK, Foreman NK. Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol. 2013;37(5):685.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8.

    Article  CAS  PubMed  Google Scholar 

  • Lahkola A, Auvinen A, Raitanen J, et al. Mobile phone use and risk of glioma in 5 north European countries. Int J Cancer. 2007;120:1769–75.

    Article  CAS  PubMed  Google Scholar 

  • Laperriere N, Zuraw L, Cairncross G, the Cancer Care Ontario Practice Guidelines Initiative Neuro-Oncology Disease Site Group. Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol. 2002;64:259–73.

    Article  PubMed  Google Scholar 

  • Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20.

    Article  Google Scholar 

  • Malmer B, Adatto P, Armstrong G, Barnholtz-Sloan J, Bernstein JL, Claus E, Davis F, Houlston R, Il'yasova D, Jenkins R, Johansen C. GLIOGENE—an international consortium to understand familial glioma. Cancer Epidemiol Prev Biomarkers. 2007;16(9):1730–4.

    Article  CAS  Google Scholar 

  • Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J. 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(9):916–26.

    Article  CAS  PubMed  Google Scholar 

  • Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008;70(5):1350–60.

    Article  CAS  PubMed  Google Scholar 

  • Mayo C, Martel MK, Marks LB, et al. Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys. 2010a;76:S28–35.

    Article  PubMed  Google Scholar 

  • Mayo C, Yorke E, Merchant TE. Radiation associated brainstem injury. Int J Radiat Oncol Biol Phys. 2010b;76:S36–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001;19:509–18.

    Article  Google Scholar 

  • Nieder C, Astner ST, Mehta MP, Grosu AL, Molls M. Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma. Am J Clin Oncol. 2008;31:300–5.

    Article  PubMed  Google Scholar 

  • Niyazi M, Brada M, Chalmers AJ, Combs SE, Erridge SC, Fiorentino A, Grosu AL, Lagerwaard FJ, Minniti G, Mirimanoff RO, Ricardi U. ESTRO-ACROP guideline “target delineation of glioblastomas”. Radiother Oncol. 2016;118(1):35–42.

    Article  PubMed  Google Scholar 

  • Noorbakhsh A, Tang JA, Marcus LP, McCutcheon B, Gonda DD, Schallhorn CS, Talamini MA, Chang DC, Carter BS, Chen CC. Gross-total resection outcomes in an elderly population with glioblastoma: a SEER-based analysis. J Neurosurg. 2014;120(1):31–9.

    Article  PubMed  Google Scholar 

  • Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(5):510–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okada H, Weller M, Huang R, et al. Immunotherapy response assessment in neuro-oncology (iRANO): a report of the RANO working group. Lancet Oncol. 2015;16(15):e534–42.

    Article  PubMed  PubMed Central  Google Scholar 

  • Paleologos TS, Dorward NL, Wadley JP, Thomas DG. Clinical validation of true frameless stereotactic biopsy: analysis of the first 125 consecutive cases. Neurosurgery. 2001;49(4):830–7.

    PubMed  CAS  Google Scholar 

  • Paulsson AK, McMullen KP, Peiffer AM, Hinson WH, Kearns WT, Johnson AJ, Lesser GJ, Ellis TL, Tatter SB, Debinski W, Shaw EG. Limited margins using modern radiotherapy techniques does not increase marginal failure rate of glioblastoma. Am J Clin Oncol. 2014;37(2):177.

    Article  PubMed  PubMed Central  Google Scholar 

  • Perry JR. Thromboembolic disease in patients with high-grade glioma. Neuro-Oncology. 2012;14(4):iv73–80.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule. Cancer. 2008;113(8):2152–7.

    Article  CAS  PubMed  Google Scholar 

  • Perry JR, Laperriere N, O’Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017;376(11):1027–37.

    Article  CAS  PubMed  Google Scholar 

  • Reardon DA, Schuster J, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Desjardins A, Ashby LS, Duic JP. ReACT: overall survival from a randomized phase II study of rindopepimut (CDX-110) plus bevacizumab in relapsed glioblastoma. Neuro Oncol. 2014;16(Suppl 5):v116

    Google Scholar 

  • Ringel F. SN1 study group, Pape H, SN1 study group, Sabel M, SN1 study group, Krex D, SN1 study group, bock HC, SN1 study group, Misch M. Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro-Oncology. 2015;18(1):96–104.

    Article  PubMed  PubMed Central  Google Scholar 

  • Roa W, Brasher PM, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22:1583e1588.

    Article  Google Scholar 

  • Romanelli P, Conti A, Pontoriero A, Ricciardi GK, Tomasello F, De Renzis C, Innocenzi G, Esposito V, Cantore G. Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme. Neurosurg Focus. 2009;27(6):E8.

    Article  PubMed  Google Scholar 

  • Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011;115(1):3–8.

    Article  PubMed  Google Scholar 

  • Sanson M, Cartalat-Carel S, Taillibert S, the ANOCEF Group, et al. Initial chemotherapy in gliomatosis cerebri. Neurology. 2004;63:270–5.

    Article  CAS  PubMed  Google Scholar 

  • Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009;27(25):4150–4.

    Article  CAS  PubMed  Google Scholar 

  • Sathornsumetee S, Rich JN, Reardon DA. Diagnosis and treatment of high grade astrocytoma. Neurol Clin. 2007;25:1111–39.

    Article  PubMed  Google Scholar 

  • Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 2011;12(11):997–1003.

    Article  PubMed  Google Scholar 

  • Stewart LA, Group GM. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002;359(9311):1011–8.

    Article  CAS  PubMed  Google Scholar 

  • 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;7:392–401.

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  CAS  PubMed  Google Scholar 

  • Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P. 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(5):459–66.

    Article  CAS  Google Scholar 

  • Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP. 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 Oncol. 2014;15(10):1100–8.

    Article  CAS  PubMed  Google Scholar 

  • Subbiah V, Bang YJ, Lassen UN, Wainberg ZA, Soria JC, Wen PY, Zenz T, Moreau P, Brunsvig P, De Braud FG, De Greve J. ROAR: a phase 2, open-label study in patients (pts) with BRAF V600E–mutated rare cancers to investigate the efficacy and safety of dabrafenib (D) and trametinib (T) combination therapy. J Clin Oncol. 2016;34(15).

    Google Scholar 

  • Theeler BJ, Gilbert MR. Advances in the treatment of newly diagnosed glioblastoma. BMC Med. 2015;13(1):293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van den Bent MJ, Brandes AA, Taphoorn MJ, 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 Oncol. 2013;31:344–50.

    Article  CAS  PubMed  Google Scholar 

  • Van Den Bent MJ, Erridge S, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Wick W, Clement PM, Baurain JF, Mason WP, Wheeler H. Results of the interim analysis of the EORTC randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q co-deletion: an Intergroup trial. Lancet. 2017;390:1645–1653

    Google Scholar 

  • Walker MD, Alexander E, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978;49:333–43.

    Article  CAS  PubMed  Google Scholar 

  • Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys. 1989;16(6):1405–9.

    Article  CAS  PubMed  Google Scholar 

  • Weller M, Stupp R, Wick W. Epilepsy meets cancer: when, why, and what to do about it? Lancet Oncol. 2012;13(9):e375–82.

    Article  PubMed  Google Scholar 

  • Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15(9):e395–403.

    Article  PubMed  Google Scholar 

  • Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18(10):1373–85.

    Article  CAS  PubMed  Google Scholar 

  • Wen PY, Schiff D, Kesari S, Drappatz J, Gigas D, Doherty L. Medical management of patients with brain tumors. J Neuro-Oncol. 2006;80:313–32.

    Article  CAS  Google Scholar 

  • Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–72.

    Article  PubMed  Google Scholar 

  • Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncology. 2003;5:79–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009;27(35):5874–80.

    Article  CAS  PubMed  Google Scholar 

  • Wick W, Meisner C, Hentschel B, Platten M, Schilling A, Wiestler B, Sabel MC, Koeppen S, Ketter R, Weiler M, Tabatabai G. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology. 2013;81(17):1515–22.

    Article  CAS  PubMed  Google Scholar 

  • Yin A-a, Zhang L-h, Cheng J-x, Dong Y, Liu B-l, et al. Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the elderly: a meta-analysis. PLoS One. 2013;8(9):e74242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You G, Sha Z, Jiang T. The pathogenesis of tumor-related epilepsy and its implications for clinical treatment. Seizure. 2012;21:153–9.

    Article  PubMed  Google Scholar 

  • Zach L, Guez D, Last D, Daniels D, Grober Y, Nissim O, Hoffmann C, Nass D, Talianski A, Spiegelmann R, Tsarfaty G. Delayed contrast extravasation MRI: a new paradigm in neuro-oncology. Neuro-Oncology. 2014;17(3):457–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao F, Li M, Kong L, Zhang G, Yu J. Delineation of radiation therapy target volumes for patients with postoperative glioblastoma: a review. OncoTargets Ther. 2016;9:3197–204.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank Saran .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Saran, F., Welsh, L., Adjogatse, D. (2018). Radiation Therapy in High-Grade Gliomas. In: Wenz, F. (eds) Radiation Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-52619-5_3-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-52619-5_3-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-52619-5

  • Online ISBN: 978-3-319-52619-5

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics