Abstract
Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.
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References
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359(5):492–507.
Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64(6):479–89.
Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United Sates in 2007–2011. Neuro Oncol. 2014;16(Suppl 4):iv1–63.
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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 Oncol. 2009;10(5):459–66.
Scott JG, Bauchet L, Fraum TJ, Nayak L, Cooper AR, Chao ST, et al. Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older. Cancer. 2012;118(22):5595–600.
Young RM, Jamshidi A, Davis G, Sherman JH. Current trends in the surgical management and treatment of adult glioblastoma. Ann Transl Med. 2015;3(9):121.
Wrensch M, Minn Y, Chew T, Bondy M, Berger MS. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol. 2002;4(4):278–99.
Wong ET, Lok E, Swanson KD. An evidence-based review of alternating electric fields therapy for malignant gliomas. Curr Treat Options Oncol. 2015;16(8):40.
Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130(Pt 10):2596–606.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003.
Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499–508.
Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19(4):764–72.
Wilson TA, Karajannis MA, Harter DH. Glioblastoma multiforme: State of the art and future therapeutics. Surg Neurol Int. 2014;8(5):64.
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807–12.
Nobusawa S, Watanabe T, Kleihues P, Ohgaki H. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009;15(19):6002–7.
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98–110.
Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9(3):157–73.
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.
Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.
Yoshida T, Kawano N, Oka H, Fujii K, Nakazato Y. Clinical cure of glioblastoma—two case reports. Neurol Med Chir (Tokyo). 2000;40(4):224–9.
Yamada S, Endo Y, Hirose T, Takada K, Usui M, Hara M. Autopsy findings in a long-term survivor with glioblastoma multiforme—case report. Neurol Med Chir (Tokyo). 1998;38(2):95–9.
Davis FG, Freels S, Grutsch J, Barlas S, Brem S. Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on surveillance, epidemiology, and end results (SEER) data, 1973–1991. J Neurosurg. 1998;88(1):1–10.
Lamborn KR, Chang SM, Prados MD. Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro Oncol. 2004;6(3):227–35.
Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, et al. 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(14):2192–202.
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.
Vuorinen V, Hinkka S, Färkkilä M, Jääskeläinen J. Debulking or biopsy of malignant glioma in elderly people—a randomised study. Acta Neurochir (Wien). 2003;145(1):5–10.
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, 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(5):392–401.
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.
Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, Raza SM, Pascual-Gallego M, Ibrahim A, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014;16(1):113–22.
Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, et al. Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg. 2012;117(5):851–9.
Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, et al. Residual tumor volume versus extent of resection: predictors of survival after surgery for glioblastoma. J Neurosurg. 2014;121(5):1115–23.
Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, et al. Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg. 2012;117(6):1032–8.
Gállego Pérez-Larraya J, Delattre JY. Management of elderly patients with gliomas. Oncologist. 2014;19(12):1258–67.
Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW, et al. An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg. 2014;120(4):846–53.
Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 1995;345(8956):1008–12.
Wangaryattawanich P, Hatami M, Wang J, Thomas G, Flanders A, Kirby J, et al. Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival. Neuro Oncol. 2015;17(11):1525–37.
Sanai N, Berger MS. Intraoperative stimulation techniques for functional pathway preservation and glioma resection. Neurosurg Focus. 2010;28(2):E1.
Krieg SM, Sollmann N, Obermueller T, Sabih J, Bulubas L, Negwer C, et al. Changing the clinical course of glioma patients by preoperative motor mapping with navigated transcranial magnetic brain stimulation. BMC Cancer. 2015;8(15):231.
Romano A, D’Andrea G, Minniti G, Mastronardi L, Ferrante L, Fantozzi LM, et al. Pre-surgical planning and MR-tractography utility in brain tumour resection. Eur Radiol. 2009;19(12):2798–808.
Abdullah KG, Lubelski D, Nucifora PG, Brem S. Use of diffusion tensor imaging in glioma resection. Neurosurg Focus. 2013;34(4):E1.
González-Darder JM, González-López P, Talamantes F, Quilis V, Cortés V, García-March G, et al. Multimodal navigation in the functional microsurgical resection of intrinsic brain tumors located in eloquent motor areas: role of tractography. Neurosurg Focus. 2010;28(2):E5.
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.
Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol. 2011;12(11):1062–70.
Wu JS, Gong X, Song YY, Zhuang DX, Yao CJ, Qiu TM, et al. 3.0-T intraoperative magnetic resonance imaging-guided resection in cerebral glioma surgery: interim analysis of a prospective, randomized, triple-blind, parallel-controlled trial. Neurosurgery. 2014;61(Suppl 1):145–54.
Brell M, Roldán P, González E, Llinàs P, Ibáñez J. Implantación de la primera resonancia intraoperatoria en un hospital de la red sanitaria pública española: experiencia inicial, viabilidad y dificultades en nuestro entorno. Neurocirugia (Astur). 2013;24(1):11–21.
Senft C, Seifert V, Hermann E, Franz K, Gasser T. Usefulness of intraoperative ultra low-field magnetic resonance imaging in glioma surgery. Neurosurgery. 2008;63(4 Suppl 2):257–66 (discussion 266–7).
Díez Valle R, Slof J, Galván J, Arza C, Romariz C, Vidal C, et al. Estudio observacional retrospectivo sobre la efectividad del ácido 5-aminolevulínico en la cirugíaa de los gliomas malignos en España (Estudio VISIONA). Neurologia. 2014;29(3):131–8.
Gil-Salú JL, Arraez MÁ, Barcia JA, Piquer J, Rodríguez de Lope A, Villalba Martínez G, et al. Recomendaciones sobre el uso de ácido 5-aminolevulínico en la cirugíaa de os gliomas malignos. Documento de consenso. Neurocirugia (Astur). 2013;24(4):163–9.
Slof J, Díez Valle R, Galván J. Análisis coste-efectividad de la cirugía del glioma maligno guiada por fluorescencia con ácido 5-aminolevulínico. Neurologia. 2015;30(3):163–8.
Eljamel S. 5-ALA fluorescence image guided resection of glioblastoma multiforme: a meta-analysis of the literature. Int J Mol Sci. 2015;16(5):10443–56.
Coburger J, Hagel V, Wirtz CR, König R. Surgery for glioblastoma: impact of the combined use of 5-aminolevulinic acid and intraoperative MRI on extent of resection and survival. PLoS One. 2015;10(6):e0131872.
Meyer FB, Bates LM, Goerss SJ, Friedman JA, Windschitl WL, Duffy JR, et al. Awake craniotomy for aggressive resection of primary gliomas located in eloquent brain. Mayo Clin Proc. 2001;76(7):677–87.
Zhang YD, Dai RY, Chen Z, Zhang YH, He XZ, Zhou J. Efficacy and safety of carmustine wafers in the treatment of glioblastoma multiforme: a systematic review. Turk Neurosurg. 2014;24(5):639–45.
Bregy A, Shah AH, Diaz MV, Pierce HE, Ames PL, Diaz D, et al. The role of Gliadel wafers in the treatment of high-grade gliomas. Expert Rev Anticancer Ther. 2013;13(12):1453–61.
Wong ET, Lok E, Gautam S, Swanson KD. Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma. Br J Cancer. 2015;113(2):232–41.
Wong ET, Lok E, Swanson KD. Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC after temozolomide and bevacizumab failure: a preliminary observation. Cancer Med. 2015;4(3):383–91.
Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, et al. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med. 1980;303(23):1323–9.
Coffey RJ, Lunsford LD, Taylor FH. Survival after stereotactic biopsy of malignant gliomas. Neurosurgery. 1988;22(3):465–73.
Nelson DF, Diener-West M, Horton J, Chang CH, Schoenfeld D, Nelson JS. Combined modality approach to treatment of malignant gliomas–re-evaluation of RTOG 7401/ECOG 1374 with long-term follow-up: a joint study of the Radiation Therapy Oncology Group and the Eastern Cooperative Oncology Group. NCI Monogr. 1988;6:279–84.
Chan JL, Lee SW, Fraass BA, Normolle DP, Greenberg HS, Junck LR, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J Clin Oncol. 2002;20(6):1635–42.
Narayana A, Yamada J, Berry S, Shah P, Hunt M, Gutin PH, et al. Intensity-modulated radiotherapy in high-grade gliomas: clinical and dosimetric results. Int J Radiat Oncol Biol Phys. 2006;64(3):892–7.
Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356(15):1527–35.
Paulino AC, Mai WY, Chintagumpala M, Taher A, Teh BS. Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys. 2008;71(5):1381–7.
Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, et al. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys. 2004;60(3):853–60.
Selker RG, Shapiro WR, Burger P, Blackwood MS, Arena VC, Gilder JC, et al. The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. Neurosurgery. 2002;51(2):343–55 (discussion 355–7).
Castro JR, Phillips TL, Prados M, Gutin P, Larson DA, Petti PL, et al. Neon heavy charged particle radiotherapy of glioblastoma of the brain. Int J Radiat Oncol Biol Phys. 1997;38(2):257–61.
Fitzek MM, Thornton AF, Rabinov JD, Lev MH, Pardo FS, Munzenrider JE, et al. Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg. 1999;91(2):251–60.
Athanassiou H, Synodinou M, Maragoudakis E, Paraskevaidis M, Verigos C, Misailidou D, et al. Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. J Clin Oncol. 2005;23(10):2372–7.
Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L. The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol. 2007;9(1):47–52 (Epub 2006 Nov 15).
Armstrong TS, Wefel JS, Wang M, Gilbert MR, Won M, Bottomley A, et al. Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma. J Clin Oncol. 2013;31(32):4076–84.
Poulsen HS, Urup T, Michaelsen SR, Staberg M, Villingshøj M, Lassen U. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients. Cancer Manag Res. 2014;26(6):373–87.
Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733–40.
Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27(5):740–5.
Iwamoto FM, Abrey LE, Beal K, Gutin PH, Rosenblum MK, Reuter VE, et al. Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology. 2009;73(15):1200–6.
Miranda PC, Mekonnen A, Salvador R, Basser PJ. Predicting the electric field distribution in the brain for the treatment of glioblastoma. Phys Med Biol. 2014;59(15):4137–47.
Turner SG, Gergel T, Wu H, Lacroix M, Toms SA. The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF™-100A system. World J Surg Oncol. 2014;22(12):162.
Lacouture ME, Davis ME, Elzinga G, Butowski N, Tran D, Villano JL, et al. Characterization and management of dermatologic adverse events with the NovoTTF-100A System, a novel anti-mitotic electric field device for the treatment of recurrent glioblastoma. Semin Oncol. 2014;41(Suppl 4):S1–14.
Omar AI. Tumor treating field therapy in combination with bevacizumab for the treatment of recurrent glioblastoma. J Vis Exp. 2014;92:e51638.
Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, et al. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg. 2003;99(3):467–73.
Hegi ME, Liu L, Herman JG, Stupp R, Wick W, Weller M, 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(25):4189–99.
Reifenberger G, Hentschel B, Felsberg J, Schackert G, Simon M, Schnell O, et al. Predictive impact of MGMT promoter methylation in glioblastoma of the elderly. Int J Cancer. 2012;131(6):1342–50.
Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009;27(25):4150–4.
Hartmann C, Hentschel B, Simon M, Westphal M, Schackert G, Tonn JC, et al. Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations. Clin Cancer Res. 2013;19(18):5146–57.
Labussière M, Boisselier B, Mokhtari K, Di Stefano AL, Rahimian A, Rossetto M, et al. Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes. Neurology. 2014;83(13):1200–6.
Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res. 2005;11(4):1462–6.
Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res. 2003;63(20):6962–70.
Rahmathulla G, Hovey EJ, Hashemi-Sadraei N, Ahluwalia MS. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges. Onco Targets Ther. 2013;15(6):371–89.
Carlsson SK, Brothers SP, Wahlestedt C. Emerging treatment strategies for glioblastoma multiforme. EMBO Mol Med. 2014;6(11):1359–70.
Hernández-Pedro NY, Rangel-López E, Magaña-Maldonado R, de la Cruz VP, del Angel AS, Pineda B, et al. Application of nanoparticles on diagnosis and therapy in gliomas. Biomed Res Int. 2013;2013:351031.
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Thanks to M. Rodríguez Miguélez for the careful review of the English version of the manuscript.
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Delgado-López, P.D., Corrales-García, E.M. Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol 18, 1062–1071 (2016). https://doi.org/10.1007/s12094-016-1497-x
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DOI: https://doi.org/10.1007/s12094-016-1497-x