Radiotherapy and concomitant temozolomide may improve survival of elderly patients with glioblastoma

Christopher A Barker, Maria Chang, Joanne F Chou, Zhigang Zhang, Kathryn Beal, Philip H Gutin, Fabio M Iwamoto, Christopher A Barker, Maria Chang, Joanne F Chou, Zhigang Zhang, Kathryn Beal, Philip H Gutin, Fabio M Iwamoto

Abstract

Survival of elderly patients with glioblastoma (GBM) is poor, but improves with tumor resection and radiotherapy (RT). Concurrent temozolomide (TMZ) chemotherapy during RT improves the survival of younger patients with GBM, but the benefit in elderly patients is unclear. Medical records of patients ≥65 years old with primary GBM, histologically confirmed at Memorial Sloan-Kettering Cancer Center and treated with RT, were reviewed. Survival was associated with patient (age, performance status), tumor (single or multiple), and treatment (extent of surgery, RT field, technique, fractionation and use of concurrent TMZ) characteristics in a multivariable Cox regression model. Grade ≥3 hematologic toxicity rates were compared to reported rates in younger patients. Median age of the 291 patients studied was 71 years. Longer survival was associated with younger age, tumor resection, and concomitant TMZ and RT (p < 0.01). Concurrent TMZ and RT improved median survival of patients with favorable prognostic factors from 12 to 21 months and from 10 to 13 months in patients 65-70 and ≥71 years old, respectively. Concomitant TMZ and RT increased the 2 year OS rate from 14 to 41 % and from 5 to 24 % in patients 65-70 and ≥71 years old, respectively. Grade 3-4 thrombocytopenia was significantly more frequent in the present cohort. Survival of elderly patients with GBM may be prolonged with the use of concomitant TMZ during RT. An ongoing randomized study will determine the benefit of this approach in a prospective fashion.

Conflict of interest statement

Conflict of interest The authors have no actual or potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Overall survival of GBM in patients with favorable prognosis (single resected tumor and RTOG RPA class 5) that underwent RT (n = 208). Patients 65–70 years old treated with RT alone are represented by a red, long-dash line. Patients 65–70 years old treated with RT and concomitant TMZ are represented by a black, solid line. Patients ≥71 years old treated with RT alone are represented by a blue, dash-dot line. Patients ≥71 years old treated with RT and concomitant TMZ are represented by a green, dot line. RT, radiation therapy; TMZ, temozolomide. p < 0.01 for log rank test between the treatment groups within the age groups
Fig. 2
Fig. 2
Overall survival of GBM in patients treated with a full course of conventionally fractionated RT (n = 245) that did (n = 98, blue, solid line) or did not (n = 147, black, dashed line) receive concurrent TMZ during RT. RT, radiation therapy; TMZ, temozolomide. p < 0.01 for log rank test between the treatment groups

References

    1. CBTRUS. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. CBTRUS; Hinsdale: 2010.
    1. Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE. Patterns of care in elderly glioblastoma patients. Ann Neurol. 2008;64:628–634.
    1. Karnofsky D, Burchenal J. The clinical evaluation of chemotherapeutic agents in cancer. In: Macleod C, editor. Evaluation of chemotherapeutic agents. Columbia University Press; New York: 1949. pp. 199–205.
    1. Vuorinen V, Hinkka S, Farkkila M, Jaaskelainen J. Debulking or biopsy of malignant glioma in elderly people—a randomised study. Acta Neurochir (Wien) 2003;145:5–10.
    1. Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Menei P, Loiseau H, Bernier V, Honnorat J, Barrie M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007;356:1527–1535.
    1. 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. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004;22:1583–1588.
    1. Phillips C, Guiney M, Smith J, Hughes P, Narayan K, Quong G. A randomized trial comparing 35 Gy in ten fractions with 60 Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma. Radiother Oncol. 2003;68:23–26.
    1. 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. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996.
    1. 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. 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;10:459–466.
    1. Athanassiou H, Synodinou M, Maragoudakis E, Paraskevaidis M, Verigos C, Misailidou D, Antonadou D, Saris G, Beroukas K, Karageorgis P. Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. J Clin Oncol. 2005;23:2372–2377.
    1. Laperriere N, O’Callaghan C, Ding K. Rationale and design for a phase III randomized controlled trial in elderly patients with glioblastoma multiforme: NCIC CTG CE.6. 13th biannual Canadian neuro-oncology meeting 2008
    1. Brandes AA, Franceschi E, Tosoni A, Benevento F, Scopece L, Mazzocchi V, Bacci A, Agati R, Calbucci F, Ermani M. Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer. 2009;115:3512–3518.
    1. Minniti G, De Sanctis V, Muni R, Filippone F, Bozzao A, Valeriani M, Osti MF, De Paula U, Lanzetta G, Tombolini V, Maurizi Enrici R. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol. 2008;88:97–103.
    1. Combs SE, Wagner J, Bischof M, Welzel T, Wagner F, Debus J, Schulz-Ertner D. Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys. 2008;70:987–992.
    1. Fiorica F, Berretta M, Colosimo C, Stefanelli A, Ursino S, Zanet E, Palmucci T, Maugeri D, Malaguarnera M, Palmucci S, Grasso M, Tirelli U, Cartei F. Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr. 2010;51(1):31–35.
    1. Mangiola A, Maira G, De Bonis P, Porso M, Pettorini B, Sabatino G, Anile C. Glioblastoma multiforme in the elderly: a therapeutic challenge. J Neurooncol. 2006;76:159–163.
    1. Sijben AE, McIntyre JB, Roldan GB, Easaw JC, Yan E, Forsyth PA, Parney IF, Magliocco AM, Bernsen H, Cairncross JG. Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol. 2008;89:97–103.
    1. Kimple RJ, Grabowski S, Papez M, Collichio F, Ewend MG, Morris DE. Concurrent temozolomide and radiation, a reasonable option for elderly patients with glioblastoma multiforme? Am J Clin Oncol. 2010;33(3):265–270.
    1. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62:679–694.
    1. Qi XS, Schultz CJ, Li XA. An estimation of radiobiologic parameters from clinical outcomes for radiation treatment planning of brain tumor. Int J Radiat Oncol Biol Phys. 2006;64:1570–1580.
    1. Curran WJ, Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE, et al. Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst. 1993;85:704–710.
    1. Scott CB, Scarantino C, Urtasun R, Movsas B, Jones CU, Simpson JR, Fischbach AJ, Curran WJ., Jr Validation and predictive power of radiation therapy oncology group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90–06. Int J Radiat Oncol Biol Phys. 1998;40:51–55.
    1. Iwamoto FM, Cooper AR, Reiner AS, Nayak L, Abrey LE. Glioblastoma in the elderly: the Memorial Sloan-Kettering Cancer Center experience (1997–2007) Cancer. 2009;115:3758–3766.
    1. Grant R, Liang BC, Page MA, Crane DL, Greenberg HS, Junck L. Age influences chemotherapy response in astrocytomas. Neurology. 1995;45:929–933.
    1. Hegi ME, Diserens A, Gorlia T, Hamou M, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. New Engl J Med. 2005;352:997–1003.
    1. Wedge SR, Porteous JK, Glaser MG, Marcus K, Newlands ES. In vitro evaluation of temozolomide combined with X-irradiation. Anticancer Drugs. 1997;8:92–97.
    1. Kil WJ, Cerna D, Burgan WE, Beam K, Carter D, Steeg PS, Tofilon PJ, Camphausen K. In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res. 2008;14:931–938.
    1. Sher DJ, Henson JW, Avutu B, Hochberg FH, Batchelor TT, Martuza RL, Barker FG, 2nd, Loeffler JS, Chakravarti A. The added value of concurrently administered temozolomide versus adjuvant temozolomide alone in newly diagnosed glioblastoma. J Neurooncol. 2008;88:43–50.

Source: PubMed

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