Skip to main content
Log in

Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience

Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60–86), median KPS was 80 (range 30–100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5–8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9–11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9–19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Fine HA et al (2005) Neoplasms of the central nervous system, chapter 39.2. In: DeVita VT, Hellman SA, Rosenburg SA (eds) Cancer: principles and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1834–1888

    Google Scholar 

  2. Paravati AJ, Heron DE, Landsittel D et al (2010) Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of radiation therapy oncology group-recursive partitioning analysis in the IMRT and temozolomide era. J Neurooncol 104(1):339–349

    Article  PubMed  Google Scholar 

  3. Li J, Wang M, Won M et al (2010) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81(3):623–630

    Article  PubMed  Google Scholar 

  4. Curran WJ, Scott CB, Horton J et al (1993) Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85(suppl. 9):704–710

    PubMed  Google Scholar 

  5. CBTRUS (2010). CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. Source: Central Brain Tumor Registry of the United States, Hinsdale. http://www.cbtrus.org

  6. Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64(suppl. 6):628–634

    Article  PubMed  Google Scholar 

  7. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(suppl. 10):987–996

    Article  PubMed  CAS  Google Scholar 

  8. Mirimanoff RO, Gorlia T, Mason W et al (2006) 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(suppl. 16):2563–2569

    Article  PubMed  CAS  Google Scholar 

  9. Roa W, Brasher PM, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22(suppl. 9):1583–1588

    Article  PubMed  CAS  Google Scholar 

  10. Macdonald DR, Cascino TL, Schold SC, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8(suppl. 7):1277–1280

    PubMed  CAS  Google Scholar 

  11. Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356(suppl. 15):1527–1535

    Article  PubMed  CAS  Google Scholar 

  12. Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD (1997) Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys 38(suppl. 1):31–36

    PubMed  CAS  Google Scholar 

  13. Slotman BJ, Kralendonk JH, van Alphen HA, Kamphorst W, Karim AB (1996) Hypofractionated radiation therapy in patients with glioblastoma multiforme: results of treatment and impact of prognostic factors. Int J Radiat Oncol Biol Phys 34(suppl. 4):895–898

    PubMed  CAS  Google Scholar 

  14. Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33(suppl. 3):201–204

    Article  PubMed  CAS  Google Scholar 

  15. Jeremic B, Shibamoto Y, Grujicic D et al (1999) Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study. J Neurooncol 44(suppl. 1):85–90

    Article  PubMed  CAS  Google Scholar 

  16. Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH (2003) Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 56(suppl. 2):519–528

    Article  PubMed  Google Scholar 

  17. Lutterbach J, Ostertag C (2005) What is the appropriate radiotherapy protocol for older patients with newly diagnosed glioblastoma? J Clin Oncol 23(suppl. 12):2869–2870

    PubMed  Google Scholar 

  18. Hulshof MC, Schimmel EC, Andries Bosch D, Gonzalez Gonzalez D (2000) Hypofractionation in glioblastoma multiforme. Radiother Oncol 54(suppl. 2):143–148

    Article  PubMed  CAS  Google Scholar 

  19. Phillips C, Guiney M, Smith J, Hughes P, Narayan K, Quong G (2003) A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma. Radiother Oncol 68(suppl. 1):23–26

    Article  PubMed  Google Scholar 

  20. Fiorica F, Berretta M, Colosimo C et al (2010) Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr 51(suppl. 1):31–35

    Article  PubMed  CAS  Google Scholar 

  21. Gerstein J, Franz K, Steinbach JP et al (2010) Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma. Radiother Oncol 97(suppl. 3):382–386

    Article  PubMed  CAS  Google Scholar 

  22. Kimple RJ, Grabowski S, Papez M, Collichio F, Ewend MG, Morris DE (2010) Concurrent temozolomide and radiation, a reasonable option for elderly patients with glioblastoma multiforme? Am J Clin Oncol 33(suppl. 3):265–270

    PubMed  CAS  Google Scholar 

  23. Minniti G, Salvati M, Arcella A et al (2011) Correlation between O(6)-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 102(suppl. 2):311–316

    Article  PubMed  CAS  Google Scholar 

  24. Combs SE, Wagner J, Bischof M et al (2008) Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys 70(suppl. 4):987–992

    Article  PubMed  Google Scholar 

  25. Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88(suppl. 1):97–103

    Article  PubMed  CAS  Google Scholar 

  26. Glantz M, Chamberlain M, Liu Q, Litofsky NS, Recht LD (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97(suppl. 9):2262–2266

    Article  PubMed  CAS  Google Scholar 

  27. Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100(suppl. 10):2208–2214

    Article  PubMed  CAS  Google Scholar 

  28. Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82(suppl. 2):207–209

    Article  PubMed  Google Scholar 

  29. Laigle-Donadey F, Figarella-Branger D, Chinot O et al (2010) Up-front temozolomide in elderly patients with glioblastoma. J Neurooncol 99(suppl. 1):89–94

    Article  PubMed  CAS  Google Scholar 

  30. Wick W, Engel C, Combs SE et al (2010) 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). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2001

  31. Malmstrom A, Gronberg BH, Stupp R et al (2010) Glioblastoma (GBM) in elderly patients: a randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2002

  32. Ewelt C, Goeppert M, Rapp M, Steiger HJ, Stummer W, Sabel M (2010) Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol 103(3):611–618

    Article  PubMed  Google Scholar 

  33. Muni R, Minniti G, Lanzetta G et al (2010) Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma. Tumori 96(suppl. 1):60–64

    PubMed  Google Scholar 

  34. Brandes AA, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115(suppl. 15):3512–3518

    Article  PubMed  CAS  Google Scholar 

  35. Minniti G, De Sanctis V, Muni R et al (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91(suppl. 1):95–100

    Article  PubMed  CAS  Google Scholar 

  36. Sijben AE, McIntyre JB, Roldan GB et al (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89(suppl. 1):97–103

    Article  PubMed  Google Scholar 

  37. Brandes AA, Vastola F, Basso U et al (2003) A prospective study on glioblastoma in the elderly. Cancer 97(suppl. 3):657–662

    Article  PubMed  Google Scholar 

  38. Bauman GS, Gaspar LE, Fisher BJ, Halperin EC, Macdonald DR, Cairncross JG (1994) A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29(suppl. 4):835–839

    PubMed  CAS  Google Scholar 

  39. Luciani A, Ascione G, Bertuzzi C et al (2010) Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. J Clin Oncol 28(suppl. 12):2046–2050

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ms. Frances Whiston and Mr. Larry Stitt, M.Sc., from the Clinical Research Unit, London Regional Cancer Program, for assistance with statistical analysis.

Conflict of interest

The authors declare no potential conflicts of interest relevant to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Barbara J. Fisher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cao, J.Q., Fisher, B.J., Bauman, G.S. et al. Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience. J Neurooncol 107, 395–405 (2012). https://doi.org/10.1007/s11060-011-0766-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0766-3

Keywords

Navigation