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Surgical resection of malignant gliomas—role in optimizing patient outcome

Nature Reviews Neurology volume 9, pages 141–151 (2013)Cite this article

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Abstract

Malignant gliomas represent one of the most devastating human diseases. Primary treatment of these tumours involves surgery to achieve tumour debulking, followed by a multimodal regimen of radiotherapy and chemotherapy. Survival time in patients with malignant glioma has modestly increased in recent years owing to advances in surgical and intraoperative imaging techniques, as well as the systematic implementation of randomized trial-based protocols and biomarker-based stratification of patients. The role and importance of several clinical and molecular factors—such as age, Karnofsky score, and genetic and epigenetic status—that have predictive value with regard to postsurgical outcome has also been identified. By contrast, the effect of the extent of glioma resection on patient outcome has received little attention, with an 'all or nothing' approach to tumour removal still taken in surgical practice. Recent studies, however, reveal that maximal possible cytoreduction without incurring neurological deficits has critical prognostic value for patient outcome and survival. Here, we evaluate state-of-the-art surgical procedures that are used in management of malignant glioma, with a focus on assessment criteria and value of tumour reduction. We highlight key surgical factors that enable optimization of adjuvant treatment to enhance patient quality of life and improve life expectancy.

Key Points

  • For patients with malignant glioma, maximal possible tumour resection (maximal surgical outcome) is critical to improve prognosis

  • Objective preoperative and postoperative tumour volumetric methods and centre-independent validated assessment criteria should be implemented as part of the standard glioma management procedure

  • Intraoperative or delayed postoperative MRI is presently the gold standard to evaluate success of malignant glioma resection

  • Intraoperative imaging techniques enable surgeons to increase the extent of tumour resection, and can be used to quantify the success of tumour removal in an unbiased manner

  • In future, patients will be stratified for inclusion in clinical trials for resection on the basis of functional tumour grading, surgical outcome (extent of tumour resection) and individual genetic characteristics

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Figure 1: Treatment algorithm for patients with glioma.
Figure 2: Functional grading and imaging of malignant gliomas and surgical planning.
Figure 3: The tumour zone model.

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References

  1. Ohgaki, H. & Kleihues, P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J. Neuropathol. Exp. Neurol. 64, 479–489 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Kohler, B. A. et al. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J. Natl Cancer Inst. 103, 714–736 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cancer Genome Atlas Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).

  4. Central Brain Tumor Registry of the United States, [online] (2012).

  5. Wen, P. Y. & Kesari, S. Malignant gliomas in adults. N. Engl. J. Med. 359, 492–507 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Stupp, R. 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. 10, 459–466 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Mirimanoff, R. O. et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J. Clin. Oncol. 24, 2563–2569 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. van den Bent, M. J., Hegi, M. E. & Stupp, R. Recent developments in the use of chemotherapy in brain tumours. Eur. J. Cancer 42, 582–588 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Keles, G. E., Lamborn, K. R. & Berger, M. S. Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome. J. Neurosurg. 95, 735–745 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Johannesen, T. B., Langmark, F. & Lote, K. Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a population-based study of 993 patients in whom tumors were diagnosed between 1970 and 1993. J. Neurosurg. 99, 854–862 (2003).

    Article  PubMed  Google Scholar 

  11. Bussiere, M. et al. Indicators of functional status for primary malignant brain tumour patients. Can. J. Neurol. Sci. 32, 50–56 (2005).

    Article  PubMed  Google Scholar 

  12. Gerstner, E. R. & Batchelor, T. T. Imaging and response criteria in gliomas. Curr. Opin. Oncol. 22, 598–603 (2010).

    Article  PubMed  Google Scholar 

  13. Gore, J. C., Manning, H. C., Quarles, C. C., Waddell, K. W. & Yankeelov, T. E. Magnetic resonance in the era of molecular imaging of cancer. Magn. Reson. Imaging 29, 587–600 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kondziolka, D., Lunsford, L. D. & Martinez, A. J. Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low-grade) astrocytoma. J. Neurosurg. 79, 533–536 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Alesch, F., Pappaterra, J., Trattnig, S. & Koos, W. T. The role of stereotactic biopsy in radiosurgery. Acta Neurochir. Suppl. 63, 20–24 (1995).

    CAS  PubMed  Google Scholar 

  16. Cohen, M. H., Johnson, J. R. & Pazdur, R. Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Clin. Cancer Res. 11, 6767–6771 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Lai, A. et al. Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J. Clin. Oncol. 29, 142–148 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Stummer, W. et al. Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. J. Neurooncol. 108, 89–97 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Perry, J. R. et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J. Clin. Oncol. 28, 2051–2057 (2010).

    CAS  PubMed  Google Scholar 

  20. Brada, M. et al. Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J. Clin. Oncol. 28, 4601–4608 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Kong, D. S. et al. Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma. Neuro Oncol. 12, 289–296 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Clarke, J. L. et al. Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J. Clin. Oncol. 27, 3861–3867 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Desjardins, A. et al. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer 118, 1302–1312 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Xu, J. F. et al. Should we reoperate for recurrent high-grade astrocytoma? J. Neurooncol. 105, 291–299 (2011).

    Article  PubMed  Google Scholar 

  25. Wick, A. et al. Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J. Clin. Oncol. 25, 3357–3361 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. van den Bent, M. J. et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J. Clin. Oncol. 27, 1268–1274 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kubben, P. L. et al. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol. 12, 1062–1070 (2011).

    Article  PubMed  Google Scholar 

  28. Van Meir, E. G. et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J. Clin. 60, 166–193 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pace, A. et al. Epilepsy in the end-of-life phase in patients with high-grade gliomas. J. Neurooncol. http://dx.doi.org/10.1007/s11060-012-0993-2.

  30. Liu, C. Q., Zhou, J., Qi, X. & Luan, G. M. Refractory temporal lobe epilepsy caused by angiocentric glioma complicated with focal cortical dysplasia: a surgical case series. J. Neurooncol. 110, 375–380 (2012).

    Article  PubMed  Google Scholar 

  31. Kubben, P. L., Postma, A. A., Kessels, A. G., van Overbeeke, J. J. & van Santbrink, H. Intraobserver and interobserver agreement in volumetric assessment of glioblastoma multiforme resection. Neurosurgery 67, 1329–1334 (2010).

    Article  PubMed  Google Scholar 

  32. Macdonald, D. R., Cascino, T. L., Schold, S. C. Jr & Cairncross, J. G. Response criteria for phase II studies of supratentorial malignant glioma. J. Clin. Oncol. 8, 1277–1280 (1990).

    Article  CAS  PubMed  Google Scholar 

  33. Wen, P. Y. et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J. Clin. Oncol. 28, 1963–1972 (2010).

    Article  PubMed  Google Scholar 

  34. Vogelbaum, M. A. et al. Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group. Neurosurgery 70, 234–243 (2012).

    Article  PubMed  Google Scholar 

  35. Sutherland, G. R. et al. A mobile high-field magnetic resonance system for neurosurgery. J. Neurosurg. 91, 804–813 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Nimsky, C., Ganslandt, O., Buchfelder, M. & Fahlbusch, R. Intraoperative visualization for resection of gliomas: the role of functional neuronavigation and intraoperative 1.5 T MRI. Neurol. Res. 28, 482–487 (2006).

    Article  PubMed  Google Scholar 

  37. Nimsky, C., Ganslandt, O., Merhof, D., Sorensen, A. G. & Fahlbusch, R. Intraoperative visualization of the pyramidal tract by diffusion-tensor-imaging-based fiber tracking. Neuroimage 30, 1219–1229 (2006).

    Article  PubMed  Google Scholar 

  38. Stummer, W. et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 7, 392–401 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Diez Valle, R. et al. Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience. J. Neurooncol. 102, 105–113 (2011).

    Article  CAS  PubMed  Google Scholar 

  40. Eyüpoglu, I. Y. et al. Improving the extent of malignant glioma resection by dual intraoperative visualization approach. PLoS ONE 7, e44885 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Senft, C. et al. Optimizing the extent of resection in eloquently located gliomas by combining intraoperative MRI guidance with intraoperative neurophysiological monitoring. J. Neurooncol. 109, 81–90 (2012).

    Article  PubMed  Google Scholar 

  42. Pia, H. W. Microsurgery of gliomas. Acta Neurochir. (Wien) 80, 1–11 (1986).

    Article  CAS  Google Scholar 

  43. Smith, A. & Burklund, C. W. Dominant hemispherectomy: preliminary report on neuropsychological sequelae. Science 153, 1280–1282 (1966).

    Article  CAS  PubMed  Google Scholar 

  44. Wilson, C. B. & Barker, M. Intrathecal transplantation of human neural tumors to the guinea pig. J. Natl Cancer Inst. 41, 1229–1240 (1968).

    CAS  PubMed  Google Scholar 

  45. McIntosh, D. A. et al. Homotransplantation of a cadaver neoplasm and a renal homograft. JAMA 192, 1171–1173 (1965).

    Article  CAS  PubMed  Google Scholar 

  46. Buell, J. F. et al. Donors with central nervous system malignancies: are they truly safe? Transplantation 76, 340–343 (2003).

    Article  PubMed  Google Scholar 

  47. Singh, S. K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821–5828 (2003).

    CAS  PubMed  Google Scholar 

  48. Sanai, N., Alvarez-Buylla, A. & Berger, M. S. Neural stem cells and the origin of gliomas. N. Engl. J. Med. 353, 811–822 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Phillips, H. S. et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9, 157–173 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Galli, R. et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64, 7011–7021 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Ricci-Vitiani, L. et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468, 824–828 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Wang, R. et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468, 829–833 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Parson, A. B. Stem cell biotech: seeking a piece of the action. Cell 132, 511–513 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Torkamani, A. & Schork, N. J. Identification of rare cancer driver mutations by network reconstruction. Genome Res. 19, 1570–1578 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Schwartzentruber, J. et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482, 226–231 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Felsberg, J. et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int. J. Cancer 129, 659–670 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Laws, E. R. et al. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J. Neurosurg. 99, 467–473 (2003).

    Article  PubMed  Google Scholar 

  58. Showalter, T. N. et al. Multifocal glioblastoma multiforme: prognostic factors and patterns of progression. Int. J. Radiat. Oncol. Biol. Phys. 69, 820–824 (2007).

    Article  PubMed  Google Scholar 

  59. Giles, G. G. & Gonzales, M. F. in Brain Tumors (eds Kaye, A. H. & Laws, E. R.) 51–70 (Churchill Livingstone, New York, 2001).

    Google Scholar 

  60. Vecht, C. J., Avezaat, C. J., van Putten, W. L., Eijkenboom, W. M. & Stefanko, S. Z. The influence of the extent of surgery on the neurological function and survival in malignant glioma. A retrospective analysis in 243 patients. J. Neurol. Neurosurg. Psychiatry 53, 466–471 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Burger, P. C. & Green, S. B. Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59, 1617–1625 (1987).

    Article  CAS  PubMed  Google Scholar 

  62. Davis, F. G., 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. 88, 1–10 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Ewelt, C. et al. Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J. Neurooncol. 103, 611–618 (2011).

    Article  PubMed  Google Scholar 

  64. Scott, J. G. et al. Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years old or older: a retrospective review of 206 cases. Neuro Oncol. 13, 428–436 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Stark, A. M., Stepper, W. & Mehdorn, H. M. Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC. Eur. J. Cancer Care (Engl.) 19, 39–44 (2010).

    Article  CAS  Google Scholar 

  66. Hassaneen, W. et al. Multiple craniotomies in the management of multifocal and multicentric glioblastoma. Clinical article. J. Neurosurg. 114, 576–584 (2011).

    Article  PubMed  Google Scholar 

  67. Barker, F. G. 2nd & Chang, S. M. Improving resection of malignant glioma. Lancet Oncol. 7, 359–360 (2006).

    Article  PubMed  Google Scholar 

  68. Louis, D. N. Molecular pathology of malignant gliomas. Annu. Rev. Pathol. 1, 97–117 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Lacroix, M. et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J. Neurosurg. 95, 190–198 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Miller, C. R., Dunham, C. P., Scheithauer, B. W. & Perry, A. Significance of necrosis in grading of oligodendroglial neoplasms: a clinicopathologic and genetic study of newly diagnosed high-grade gliomas. J. Clin. Oncol. 24, 5419–5426 (2006).

    Article  PubMed  Google Scholar 

  71. Homma, T. et al. Correlation among pathology, genotype, and patient outcomes in glioblastoma. J. Neuropathol. Exp. Neurol. 65, 846–854 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Noch, E. & Khalili, K. Molecular mechanisms of necrosis in glioblastoma: the role of glutamate excitotoxicity. Cancer Biol. Ther. 8, 1791–1797 (2009).

    Article  CAS  PubMed  Google Scholar 

  73. Nelson, J. S. et al. Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas. Cancer 52, 550–554 (1983).

    Article  CAS  PubMed  Google Scholar 

  74. Muragaki, Y. et al. Usefulness of intraoperative magnetic resonance imaging for glioma surgery. Acta Neurochir. Suppl. 98, 67–75 (2006).

    Article  CAS  PubMed  Google Scholar 

  75. Mehdorn, H. M. et al. High-field iMRI in glioblastoma surgery: improvement of resection radicality and survival for the patient? Acta Neurochir. Suppl. 109, 103–106 (2011).

    Article  PubMed  Google Scholar 

  76. Oszvald, A. et al. Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age. J. Neurosurg. 116, 357–364 (2012).

    Article  PubMed  Google Scholar 

  77. Kuhnt, D. et al. Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol. 13, 1339–1348 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Stummer, W. et al. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 62, 564–576 (2008).

    Article  PubMed  Google Scholar 

  79. Simpson, J. R. 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. 26, 239–244 (1993).

    Article  CAS  PubMed  Google Scholar 

  80. Rostomily, R. C. et al. Multimodality management of recurrent adult malignant gliomas: results of a phase II multiagent chemotherapy study and analysis of cytoreductive surgery. Neurosurgery 35, 378–388 (1994).

    Article  CAS  PubMed  Google Scholar 

  81. Sanai, N., Polley, M. Y., McDermott, M. W., Parsa, A. T. & Berger, M. S. An extent of resection threshold for newly diagnosed glioblastomas. J. Neurosurg. 115, 3–8 (2011).

    Article  PubMed  Google Scholar 

  82. Wirtz, C. R. et al. Clinical evaluation and follow-up results for intraoperative magnetic resonance imaging in neurosurgery. Neurosurgery 46, 1112–1120 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Stummer, W. et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42, 518–525 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Stummer, W. et al. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J. Neurosurg. 93, 1003–1013 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. De Witt Hamer, P. C., Robles, S. G., Zwinderman, A. H., Duffau, H. & Berger, M. S. Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. J. Clin. Oncol. 30, 2559–2565 (2012).

    Article  PubMed  Google Scholar 

  86. Voorhies, R. M. et al. Intraoperative localization of subcortical brain tumors: further experience with B-mode real-time sector scanning. Neurosurgery 12, 189–194 (1983).

    Article  CAS  PubMed  Google Scholar 

  87. Kanno, H. et al. Intraoperative power Doppler ultrasonography with a contrast-enhancing agent for intracranial tumors. J. Neurosurg. 102, 295–301 (2005).

    Article  PubMed  Google Scholar 

  88. Grant, W. E., Hopper, C., MacRobert, A. J., Speight, P. M. & Bown, S. G. Photodynamic therapy of oral cancer: photosensitisation with systemic aminolaevulinic acid. Lancet 342, 147–148 (1993).

    Article  CAS  PubMed  Google Scholar 

  89. Regula, J. et al. Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX—a pilot study. Gut 36, 67–75 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Schneider, J. P. et al. Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme—a quantitative radiological analysis. Neuroradiology 47, 489–500 (2005).

    Article  PubMed  Google Scholar 

  91. Senft, C. et al. Influence of iMRI-guidance on the extent of resection and survival of patients with glioblastoma multiforme. Technol. Cancer Res. Treat. 9, 339–346 (2010).

    Article  PubMed  Google Scholar 

  92. Senft, C. et al. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 12, 997–1003 (2011).

    Article  PubMed  Google Scholar 

  93. McGirt, M. J. et al. Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J. Neurosurg. 110, 156–162 (2009).

    Article  PubMed  Google Scholar 

  94. Vuorinen, V., Hinkka, S., Farkkila, M. & Jaaskelainen, J. Debulking or biopsy of malignant glioma in elderly people—a randomised study. Acta Neurochir. (Wien) 145, 5–10 (2003).

    Article  CAS  Google Scholar 

  95. Sawaya, R. et al. Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery 42, 1044–1055 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Hegi, M. E. 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. 26, 4189–4199 (2008).

    Article  CAS  PubMed  Google Scholar 

  97. Songtao, Q. et al. IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci. 103, 269–273 (2012).

    Google Scholar 

  98. Weller, M. et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat. Rev. Neurol. 6, 39–51 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Savaskan, N. E., Fingerle-Rowson, G., Buchfelder, M. & Eyüpoglu, I. Y. Brain miffed by macrophage migration inhibitory factor. Int. J. Cell Biol. 2012, 139573 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Engelhorn, T. et al. Cellular characterization of the peritumoral edema zone in malignant brain tumors. Cancer Sci. 100, 1856–1862 (2009).

    Article  CAS  PubMed  Google Scholar 

  101. Savaskan, N. E. et al. Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema. Nat. Med. 14, 629–632 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Savaskan, N. E. et al. Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas. Oncogene 30, 43–53 (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Buckingham, S. C. et al. Glutamate release by primary brain tumors induces epileptic activity. Nat. Med. 17, 1269–1274 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Jain, R. K. et al. Angiogenesis in brain tumours. Nat. Rev. Neurosci. 8, 610–622 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Purow, B. & Schiff, D. Advances in the genetics of glioblastoma: are we reaching critical mass? Nat. Rev. Neurol. 5, 419–426 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Li, A. et al. Unsupervised analysis of transcriptomic profiles reveals six glioma subtypes. Cancer Res. 69, 2091–2099 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Verhaak, R. G. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. MacDonald, T. J. et al. Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet. 29, 143–152 (2001).

    Article  CAS  PubMed  Google Scholar 

  109. Tso, C. L. et al. Distinct transcription profiles of primary and secondary glioblastoma subgroups. Cancer Res. 66, 159–167 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Ruano, Y. et al. Worse outcome in primary glioblastoma multiforme with concurrent epidermal growth factor receptor and p53 alteration. Am. J. Clin. Pathol. 131, 257–263 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. Jenkins, R. B. et al. 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. 66, 9852–9861 (2006).

    Article  CAS  PubMed  Google Scholar 

  112. Cairncross, G. et al. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J. Clin. Oncol. 24, 2707–2714 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. Weller, M. et al. Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? Clin. Cancer Res. 13, 6933–6937 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Belanich, M. et al. Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. 56, 783–788 (1996).

    CAS  PubMed  Google Scholar 

  115. Jaeckle, K. A. et al. Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J. Clin. Oncol. 16, 3310–3315 (1998).

    Article  CAS  PubMed  Google Scholar 

  116. Esteller, M. et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. 343, 1350–1354 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Rivera, A. L. et al. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol. 12, 116–121 (2010).

    Article  CAS  PubMed  Google Scholar 

  118. Hegi, M. E. et al. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin. Cancer Res. 10, 1871–1874 (2004).

    Article  CAS  PubMed  Google Scholar 

  119. Stojic, L. et al. Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase. Genes Dev. 18, 1331–1344 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Hegi, M. E. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 352, 997–1003 (2005).

    Article  CAS  PubMed  Google Scholar 

  121. Yan, H. et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765–773 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Parsons, D. W. et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807–1812 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Chowdhury, R. et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 12, 463–469 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Metellus, P. et al. IDH mutation status impact on in vivo hypoxia biomarkers expression: new insights from a clinical, nuclear imaging and immunohistochemical study in 33 glioma patients. J. Neurooncol. 105, 591–600 (2011).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all members of our neuro-oncology laboratory team for continuous support and clinical and experimental data discussion. The Tumorzentrum Erlangen-Nürnberg, particularly P. Karl and S. Petsch, are acknowledged for continuous collaboration and clinical data exchange. K. Friedlein is gratefully acknowledged for initial comorbidity analysis. We further thank P. Grummich for functional imaging, F. Bittner for digital artwork, and J. Halstead (Syngenta, Basel, Switzerland) for helpful comments. N. Hore is gratefully acknowledged for editing and critical suggestions on the manuscript. This study was supported by the German Research Foundation (DFG Grant Ey94/2-1 awarded to I. Y. Eyüpoglu).

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  1. Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen, D-91054, Germany

    Ilker Y. Eyüpoglu, Michael Buchfelder & Nic E. Savaskan

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  1. Ilker Y. Eyüpoglu
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  2. Michael Buchfelder
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All authors contributed equally to researching data for the article, discussion of the content, writing the article, and to review and editing of the manuscript before submission.

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Correspondence to Ilker Y. Eyüpoglu.

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Eyüpoglu, I., Buchfelder, M. & Savaskan, N. Surgical resection of malignant gliomas—role in optimizing patient outcome. Nat Rev Neurol 9, 141–151 (2013). https://doi.org/10.1038/nrneurol.2012.279

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