Treatment of Glioblastoma in “Elderly” Patients

CNS Malignancies

Opinion statement

The number of patients over 65 with newly diagnosed glioblastoma is anticipated to increase significantly in coming decades as a result of demographic shifts in the United States. Older patients with this disease have a significantly worse life expectancy compared with patients under 65. Mounting clinical evidence suggests that fit elderly patients with glioblastoma benefit from the addition of temozolomide to standard surgery and radiation. As a result, for healthy patients over 65 we recommend maximal surgical debulking followed by involved-field radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide (75 mg/m2/day) and 6 months of adjuvant temozolomide (150–200 mg/m2/day for five consecutive days/month). Patients over 65 with newly diagnosed or recurrent glioblastoma should also be considered for inclusion in clinical trials. MGMT is a validated prognostic marker in patients over 65 and may be useful in clinical decision-making in frail elderly patients. Age alone should not be a factor in deciding how patients with newly diagnosed glioblastoma should be treated.

References Recommended and Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Yabroff KR, Lamont EB, Mariotto A, et al. Cost of care for elderly cancer patients in the United States. J Natl Cancer Inst. 2008;100(9):630–41.PubMedCrossRefGoogle Scholar
  2. 2.
    Centers for Disease Control. Public health and aging: trends in aging, United States and worldwide. Available at Accessed November 2010.
  3. 3.
    Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res. 2004;64(19):6892–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Wrensch M, Minn Y, Chew T, et al. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol. 2002;4(4):278–99.PubMedGoogle Scholar
  5. 5.
    Curran Jr WJ, Scott CB, Horton J, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993;85(9):704–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Li J, Wang M, Won M, et al. Validation and simplification of the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification for Glioblastoma. Int J Radiat Oncol Biol Phys. 2010; Sep 30.Google Scholar
  7. 7.
    Buckner JC. Factors influencing survival in high grade gliomas. Semin Oncol. 2003;30(6 Suppl 19):10–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Scott JN, Rewcastle NB, Brasher PM, et al. Long-term glioblastoma multiforme survivors: a population-based study. Can J Neurol Sci. 1998;25(3):197–201.PubMedGoogle Scholar
  9. 9.•
    Grossman SA, Ye X, Piantadosi S, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010; 15;16(8):2443–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Westphal M, Ram Z, Riddle V, et al. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir Wien. 2006;148(3):269–75.PubMedCrossRefGoogle Scholar
  11. 11.
    Attenello FJ, Mukherjee D, Datoo G, et al. Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10-year institutional experience. Ann Surg Oncol. 2008;15(10):2887–93.PubMedCrossRefGoogle Scholar
  12. 12.
    Kelly PJ, Daumas-Duport C, Kispert DB, et al. Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg. 1987;66(6):865–74.PubMedCrossRefGoogle Scholar
  13. 13.
    Halperin EC, Bentel G, Heinz ER, et al. Radiation therapy treatment planning in supratentorial glioblastoma multiforme: an analysis based on post mortem topographic anatomy with CT correlations. Int J Radiat Oncol Biol Phys. 1989;17(6):1347–50.PubMedCrossRefGoogle Scholar
  14. 14.
    Simpson JR, Horton J, Scott C, et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys. 1993;26(2):239–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys. 1979;5(10):1725–31.PubMedGoogle Scholar
  16. 16.
    Souhami L, Seiferheld W, Brachman D, 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Welsh J, Sanan A, Gabayan AJ, et al. GliaSite brachytherapy boost as part of initial treatment of glioblastoma multiforme: a retrospective multi-institutional pilot study. Int J Radiat Oncol Biol Phys. 2007;68(1):159–65.PubMedCrossRefGoogle Scholar
  18. 18.
    Coughlin C, Scott C, Langer C, et al. Phase II, two-arm RTOG trial (94–11) of bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 Gy) based on tumor volume (> 20 or < or = 20 cm(2), respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients. Int J Radiat Oncol Biol Phys. 2000;48(5):1351–8.PubMedCrossRefGoogle Scholar
  19. 19.••
    Stupp R, Hegi ME, Mason WP, 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.PubMedCrossRefGoogle Scholar
  20. 20.
    Walker MD, Alexander Jr 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(3):333–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Gorlia T, van den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol. 2008;9(1):29–38.PubMedCrossRefGoogle Scholar
  22. 22.
    Weller M, Felsberg J, Hartmann C, et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol. 2009;27(34):5743–50.PubMedCrossRefGoogle Scholar
  23. 23.•
    Minniti G, Salvati M, Arcella A, et al. Correlation between O(6)-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol. 2010; Aug 5. An analysis of 83 patients older than 70 suggesting that MGMT status may outweigh age as a prognostic factor in the elderly population.Google Scholar
  24. 24.
    Batchelor TT, Betensky RA, Esposito JM, et al. Age-dependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res. 2004;10(1 Pt 1):228–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Iwamoto FM, Reiner AS, Panageas KS, et al. Patterns of care in elderly glioblastoma patients. Ann Neurol. 2008;64(6):628–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Scott J, Tsai YY, Chinnaiyan P, et al. Effectiveness of Radiotherapy for Elderly Patients with Glioblastoma. Int J Radiat Oncol Biol Phys. 2010; Jul 31 (e-pub ahead of print).Google Scholar
  27. 27.
    Iwamoto FM, Cooper AR, Reiner AS, et al. Glioblastoma in the elderly: the Memorial Sloan-Kettering Cancer Center Experience (1997–2007). Cancer. 2009;115(16):3758–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Kelly PJ, Hunt C. The limited value of cytoreductive surgery in elderly patients with malignant gliomas. Neurosurgery. 1994;34(1):62–6. discussion 66–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Chaichana KL, Garzon-Muvdi T, Parker S, et al. Supratentorial Glioblastoma Multiforme: The Role of Surgical Resection Versus Biopsy Among Older Patients. Ann Surg Oncol. 2010; Aug 10. [Epub ahead of print].Google Scholar
  30. 30.
    Vuorinen V, Hinkka S, Färkkilä M, et al. Debulking or biopsy of malignant glioma in elderly people - a randomised study. Acta Neurochir Wien. 2003;145(1):5–10.PubMedCrossRefGoogle Scholar
  31. 31.
    Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356(15):1527–35.PubMedCrossRefGoogle Scholar
  32. 32.
    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(9):1583–8.PubMedCrossRefGoogle Scholar
  33. 33.•
    Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22(6):633–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Malmstrom M, Gronberg BH, Stupp R, et al. Glioblastoma in elderly patients: a randomized controlled trial comparing survival in patients treated with 6-week radiotherapy versus hypofractionated RT over two weeks versus temozolomide single-agent chemotherapy. J Clin Oncol. 2010; Sep;18(S): LBA 2007.Google Scholar
  35. 35.
    Wick W, Engel C, Combs S, et al. NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved-field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (Methusalem). J Clin Oncol. 2010; Sep;18(S): LBA 2001.Google Scholar
  36. 36.
    Minniti G, De Sanctis V, Muni R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol. 2008;88(1):97–103.PubMedCrossRefGoogle Scholar
  37. 37.
    Surveillance, Epidemiology and End Results Database: Brain cancer mortality trends in the U.S., 1997–2007. Available at Accessed December 2010.
  38. 38.
    Barker CA, Chang M, Chou JF, et al. Concurrent temozolomide increases survival but incrases toxicity in elderly patients with glioblastoma multiforme treated with standard or abbreviated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(3):S167.Google Scholar
  39. 39.
    Brandes AA, Vastola F, Basso U, et al. A prospective study on glioblastoma in the elderly. Cancer. 2003;97(3):657–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Combs SE, Wagner J, Bischof M, et al. Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys. 2008;70(4):987–92.PubMedCrossRefGoogle Scholar
  41. 41.
    Fiorica F, Berretta M, Colosimo C, et al. Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr. 2010;51(1):31–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.The Brain Cancer ProgramSidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA

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