Abstract
To evaluate the safety and efficacy of hypofractionated radiotherapy (RT) with a standard temozolomide (TMZ) regimen for adults with newly diagnosed glioblastoma multiforme (GBM), twenty-six consecutive adults (range 39–79 years) who met our enrollment criteria received short courses of hypofractionated RT (45 Gy in 15 fractions over three weeks) with concomitant TMZ at 75 mg/m2/d. After 28 days, TMZ was maintained at 150–200 mg/m2/d on five days for 12 cycles or until tumor progression or unacceptable toxicity. The primary end point was determined by overall survival (OS) and toxicity. Secondary assessed end points were: progression-free survival (PFS) at six months, health-related quality of life (HRQOL), and pseudo-progression. We assessed HRQOL by use of the Karnofsky performance status (KPS) and the Functional Assessment of Cancer Therapy–Brain (FACT-Br) Subscale. All 26 patients were evaluated for OS, PFS, and HRQOL. At a median follow-up of 20 months, the median OS was 15.6 months (95% confidence interval 9.0–22.2 months) with acceptable toxicity. PFS rate at six months was 65%. KPS and FACT-Br Subscale scores did not decline after this procedure. Pseudo-progression occurred in two (8%) patients. Adult patients with GBM benefitted from favorable OS and PFS rate as a result of the hypofractionated RT with TMZ. An additional advantage is that this procedure may reduce the course of treatment. Further studies using this procedure are warranted.
Similar content being viewed by others
References
Devaux BC, O’Fallon JR, Kelly PJ (1993) Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 78:767–775
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
Hall EJ (ed) (1994) Radiobiology for the radiologist, 4th edn. Lippincott, Philadelphia, PA, pp 138–160
Garcia LM, Wilkins DE, Raaphorst GP (2007) Alpha/beta ratio: a dose range dependence study. Int J Radiat Oncol Biol Phys 67:587–593
Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:1583–1588
Glinski B (1993) Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial. J Neurooncol 16:167–172
Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD Jr (1997) Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys 38:31–36
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 34:895–898
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Nieder C, Andratschke N, Wiedenmann N, Busch R, Grosu AL, Molls M (2004) Radiotherapy for high-grade gliomas. Does altered fractionation improve the outcome? Strahlenther Onkol 180:401–407
Rades D, Heisterkamp C, Huttenlocher S, Bohlen G, Dunst J, Haatanen T, Schild SE (2010) Dose escalation of whole-brain radiotherapy for brain metastases from melanoma. Int J Radiat Oncol Biol Phys 77:537–541
Kil WJ, Cerna D, Burgan WE, Beam K, Carter D, Steeg PS, Tofilon PJ, Camphausen K (2008) In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res 14:931–938
Bobola MS, Kolstoe DD, Blank A, Silber JR (2010) Minimally cytotoxic doses of temozolomide produce radiosensitization in human glioblastoma cells regardless of MGMT expression. Mol Cancer Ther 9:1208–1218
Chang EL, Akyurek S, Avalos T, Rebueno N, Spicer C, Garcia J, Famiglietti R, Allen PK, Chao KS, Mahajan A, Woo SY, Maor MH (2007) Evaluation of peritumoral edema in the delineation of radiotherapy clinical target volumes for glioblastoma. Int J Radiat Oncol Biol Phys 68:144–150
Karim AB, Kralendonk JH (1991) Pitfalls and controversies in the treatment of gliomas. In: Karim AB, Laws ER Jr (eds) Glioma. Principles and practice in neuro-oncology. Springer Verlag, Berlin, pp 1–16
Floyd NS, Woo SY, Teh BS, Prado C, Mai WY, Trask T, Gildenberg PL, Holoye P, Augspurger ME, Carpenter LS, Lu HH, Chiu JK, Grant WH III, Butler EB (2004) Hypofractionated intensity-modulated radiotherapy for primary glioblastoma multiforme. Int J Radiat Oncol Biol Phys 58:721–726
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group (2009) 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
Chamberlain MG, Glantz MJ, Chalamer L, Van Horn A, Sloan AE.: Early necrosis following concurrent temozolomide and radiotherapy in adult patients with glioblastoma. J Clin Oncol 2006 ASCO Meeting, p 18S
Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461
Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M, Lam K, Davey P, Tsao MN (2010) Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci 37:36–42
Mayo C, Maeter MK, Marks LB, Flickinger J, Nam J, Kirkpatrick L (2010) Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 76:S28–S35
Weitzner MA, Meyers CA, Gelke CK, Byrne KS, Cella DF, Levin VA (1995) The Functional Assessment of Cancer Therapy (FACT) scale. Development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer 75:1151–1161
Cella D, Paul D, Yount S, Winn R, Chang CH, Banik D, Weeks J (2003) What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN). Cancer Invest 21:526–535
Acknowledgements
The authors wish to thank Dr Hiroshi Otsubo for preparing the revised version of the manuscript and Carol L. Squires for her editorial services for which she received compensation. We appreciate the reviewers’ comments and hope that we have addressed their questions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Terasaki, M., Eto, T., Nakashima, S. et al. A pilot study of hypofractionated radiation therapy with temozolomide for adults with glioblastoma multiforme. J Neurooncol 102, 247–253 (2011). https://doi.org/10.1007/s11060-010-0306-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-010-0306-6