Radiation Oncology pp 1-26 | Cite as
Radiation Therapy in High-Grade Gliomas
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.
Keywords
Radiotherapy High grade glioma Malignant glioma Personalised medicine Target volume definitionReferences
- 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
- Belozerov VE, Van Meir EG. Inhibitors of hypoxia-inducible factor-1 signaling. Curr Opin Investig Drugs. 2006;7:1067–76.PubMedGoogle Scholar
- Bhandare N, Jackson A, Eisbruch A, et al. Radiation therapy and hearing loss. Int J Radiat Oncol Biol Phys. 2010;76:S50–7.CrossRefPubMedPubMedCentralGoogle Scholar
- Bokstein F, Shpigel S, Blumenthal DT. Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors. Cancer. 2008;112(10):2267–73.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Chamberlain MC. Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol. 2011;5:117.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
- Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin. 2007;25:8678–90.CrossRefGoogle Scholar
- Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007;21:2683–710.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Hardesty DA, Sanai N. The value of glioma extent of resection in the modern neurosurgical era. Front Neurol. 2012;3:140.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Herrlinger U, Felsberg J, Küker W, et al. Gliomatosis cerebri: molecular pathology and clinical course. Ann Neurol. 2002;52:390–9.CrossRefPubMedGoogle Scholar
- Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology. 1980;30(9):907.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Hottinger AF, Levivier M, Negretti L, et al. PET imaging in glioma. The neurooncologist’s expectations. PET Clin. 2013;8:117–28.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle Scholar
- Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008;70(5):1350–60.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Mayo C, Yorke E, Merchant TE. Radiation associated brainstem injury. Int J Radiat Oncol Biol Phys. 2010b;76:S36–41.CrossRefPubMedPubMedCentralGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.PubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle Scholar
- Perry JR. Thromboembolic disease in patients with high-grade glioma. Neuro-Oncology. 2012;14(4):iv73–80.PubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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):v116Google 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Sanson M, Cartalat-Carel S, Taillibert S, the ANOCEF Group, et al. Initial chemotherapy in gliomatosis cerebri. Neurology. 2004;63:270–5.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
- Sathornsumetee S, Rich JN, Reardon DA. Diagnosis and treatment of high grade astrocytoma. Neurol Clin. 2007;25:1111–39.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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;390:1645–1653Google 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle Scholar
- You G, Sha Z, Jiang T. The pathogenesis of tumor-related epilepsy and its implications for clinical treatment. Seizure. 2012;21:153–9.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.Google Scholar