Skip to main content
Top
Published in: Journal of Neuro-Oncology 2/2016

01-09-2016 | Clinical Study

Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study

Authors: Stefano Bracci, Florence Laigle-Donadey, Kathryn Hitchcock, Alberto Duran-Peña, Soledad Navarro, Antoine Chevalier, Julian Jacob, Idriss Troussier, Jean-Yves Delattre, Jean-Jacques Mazeron, Khê Hoang-Xuan, Loïc Feuvret

Published in: Journal of Neuro-Oncology | Issue 2/2016

Login to get access

Abstract

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60–90). After a median follow-up of 5.8 months (IQR 3.7–13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5–19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9–71.2 %) and 6.6 % (95 % CI 1.0− 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9–7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4–52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among “very elderly” patients affected by GBM. Patients 80 and older should be considered for management based on RT.
Literature
1.
go back to reference Ostrom QT, Gittleman H, Fulop J, Liu M, Blonda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol 17:iv1–iv62CrossRefPubMed Ostrom QT, Gittleman H, Fulop J, Liu M, Blonda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol 17:iv1–iv62CrossRefPubMed
2.
go back to reference Ferguson M, Rodrigues G, Cao J, Bauman G (2014) Management of high-grade gliomas in the elderly. Semin Radiat Oncol 24:279–288CrossRefPubMed Ferguson M, Rodrigues G, Cao J, Bauman G (2014) Management of high-grade gliomas in the elderly. Semin Radiat Oncol 24:279–288CrossRefPubMed
3.
go back to reference Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E (2001) A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:100–107CrossRefPubMed Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E (2001) A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:100–107CrossRefPubMed
4.
go back to reference Barnholtz-Sloan JS, Williams VL, Maldonado JL, Shahani D, Stockwell HG, Chamberlain M, Sloan AE (2008) Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg 108:642–648CrossRefPubMed Barnholtz-Sloan JS, Williams VL, Maldonado JL, Shahani D, Stockwell HG, Chamberlain M, Sloan AE (2008) Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg 108:642–648CrossRefPubMed
5.
go back to reference Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628–634CrossRefPubMed Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628–634CrossRefPubMed
6.
go back to reference Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, Lacombe D, Stupp R (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE.3. Lancet Oncol 9:29–38CrossRefPubMed Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, Lacombe D, Stupp R (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE.3. Lancet Oncol 9:29–38CrossRefPubMed
7.
go back to reference 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 10:459–466CrossRefPubMed 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 10:459–466CrossRefPubMed
8.
go back to reference Li J, Wang M, Won M, Shaw EG, Coughlin C, Curran WJ Jr, Mehta MP (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81:623–630CrossRefPubMed Li J, Wang M, Won M, Shaw EG, Coughlin C, Curran WJ Jr, Mehta MP (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81:623–630CrossRefPubMed
9.
go back to reference Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, FrenayM, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Meneï P, Loiseau H, Bernier V, Honnorat J, Barrié M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY, Association of French-Speaking Neuro-Oncologists (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, FrenayM, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Meneï P, Loiseau H, Bernier V, Honnorat J, Barrié M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY, Association of French-Speaking Neuro-Oncologists (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed
10.
go back to reference 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 22:1583–1588CrossRefPubMed 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 22:1583–1588CrossRefPubMed
11.
go back to reference Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M (2012) NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715CrossRefPubMed Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M (2012) NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715CrossRefPubMed
12.
go back to reference Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R, Nordic Clinical Brain Tumour Study Group (NCBTSG) (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926CrossRefPubMed Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R, Nordic Clinical Brain Tumour Study Group (NCBTSG) (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926CrossRefPubMed
13.
go back to reference Laperriere N, Weller M, Stupp R, Perry JR, Brandes AA, Wick W, van den Bent MJ (2013) Optimal management of elderly patients with glioblastoma. Cancer Treat Rev 39:350–357CrossRefPubMed Laperriere N, Weller M, Stupp R, Perry JR, Brandes AA, Wick W, van den Bent MJ (2013) Optimal management of elderly patients with glioblastoma. Cancer Treat Rev 39:350–357CrossRefPubMed
14.
go back to reference Perry JR, O’Callaghan CJ, Ding K, Roa W, Mason WP, Cairncross JG, Brandes AA, Menten J, Phillips C, Fay MF, Nishikawa R, Winch C, Laperriere N (2014) A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677). Neuro Oncol 16 (suppl 3):iii46CrossRef Perry JR, O’Callaghan CJ, Ding K, Roa W, Mason WP, Cairncross JG, Brandes AA, Menten J, Phillips C, Fay MF, Nishikawa R, Winch C, Laperriere N (2014) A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677). Neuro Oncol 16 (suppl 3):iii46CrossRef
15.
go back to reference Brandes AA, Vastola F, Basso U, Berti F, Pinna G, Rotilio A, Gardiman M, Scienza R, Monfardini S, Ermani M (2003) A prospective study on glioblastoma in the elderly. Cancer 97:657–662CrossRefPubMed Brandes AA, Vastola F, Basso U, Berti F, Pinna G, Rotilio A, Gardiman M, Scienza R, Monfardini S, Ermani M (2003) A prospective study on glioblastoma in the elderly. Cancer 97:657–662CrossRefPubMed
16.
go back to reference Wen PY, MacDonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMed Wen PY, MacDonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972CrossRefPubMed
17.
go back to reference Idbaih A, Taillibert S, Simon JM, Psimaras D, Schneble HM, Lopez S, Lang P, Toubiana T, Feuvret L, Delattre JY, Mazeron JJ (2008) Short course of radiation therapy in elderly patients with glioblastoma multiforme. Cancer Radiother 12:788–792CrossRefPubMed Idbaih A, Taillibert S, Simon JM, Psimaras D, Schneble HM, Lopez S, Lang P, Toubiana T, Feuvret L, Delattre JY, Mazeron JJ (2008) Short course of radiation therapy in elderly patients with glioblastoma multiforme. Cancer Radiother 12:788–792CrossRefPubMed
18.
go back to reference Piccirilli M, Bistazzoni S, Gagliardi FM, Landi A, Santoro A, Giangaspero F, Salvati M (2006) Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients olderthan 80 years. Tumori 92:98–103PubMed Piccirilli M, Bistazzoni S, Gagliardi FM, Landi A, Santoro A, Giangaspero F, Salvati M (2006) Treatment of glioblastoma multiforme in elderly patients. Clinico-therapeutic remarks in 22 patients olderthan 80 years. Tumori 92:98–103PubMed
19.
go back to reference Uzuka T, Asano K, Sasajima T, Sakurada K, Kumabe T, Beppu T, Ichikawa M, Kitanaka C, Aoki H, Saito K, Ogasawara K, Tominaga T, Mizoi K, Ohkuma H, Fujii Y, Kayama T, Tohoku Brain Tumor Study Group (2014) Treatment outcomes in glioblastoma patients aged 76 years or older: a multicenter retrospective cohort study. J Neurooncol 116:299–306CrossRefPubMed Uzuka T, Asano K, Sasajima T, Sakurada K, Kumabe T, Beppu T, Ichikawa M, Kitanaka C, Aoki H, Saito K, Ogasawara K, Tominaga T, Mizoi K, Ohkuma H, Fujii Y, Kayama T, Tohoku Brain Tumor Study Group (2014) Treatment outcomes in glioblastoma patients aged 76 years or older: a multicenter retrospective cohort study. J Neurooncol 116:299–306CrossRefPubMed
20.
go back to reference Pérez-Larraya JG, Ducray F, Chinot O, Catry-Thomas I, Taillandier L, Guillamo JS, Campello C, Monjour A, Cartalat-Carel S, Barrie M, Huchet A, Beauchesne P, Matta M, Mokhtari K, Tanguy ML, Honnorat J, Delattre JY (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol 29:3050–3055CrossRef Pérez-Larraya JG, Ducray F, Chinot O, Catry-Thomas I, Taillandier L, Guillamo JS, Campello C, Monjour A, Cartalat-Carel S, Barrie M, Huchet A, Beauchesne P, Matta M, Mokhtari K, Tanguy ML, Honnorat J, Delattre JY (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol 29:3050–3055CrossRef
21.
go back to reference Minniti G, Lanzetta G, Scaringi C, Caporello P, Salvati M, Arcella A, De Sanctis V, Giangaspero F, Enrici RM (2012) Phase II study of short-course radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma. Int J Radiat Oncol Biol Phys 83:93–99CrossRefPubMed Minniti G, Lanzetta G, Scaringi C, Caporello P, Salvati M, Arcella A, De Sanctis V, Giangaspero F, Enrici RM (2012) Phase II study of short-course radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma. Int J Radiat Oncol Biol Phys 83:93–99CrossRefPubMed
22.
go back to reference Hegi ME, Diserens AC, Gorlia T, Hamou MF, 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 (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed Hegi ME, Diserens AC, Gorlia T, Hamou MF, 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 (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed
23.
go back to reference Weller M1, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME (2010) MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol 6:39–51CrossRefPubMed Weller M1, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME (2010) MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol 6:39–51CrossRefPubMed
24.
go back to reference Minniti G, Scaringi C, Lanzetta G, Terrenato I, Esposito V, Arcella A, Pace A, Giangaspero F, Bozzao A, Enrici RM (2015) standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol Biol Phys 91:109–115CrossRef Minniti G, Scaringi C, Lanzetta G, Terrenato I, Esposito V, Arcella A, Pace A, Giangaspero F, Bozzao A, Enrici RM (2015) standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol Biol Phys 91:109–115CrossRef
25.
go back to reference Arvold ND, Wang Y, Zigler C, Schrag D, Dominici F (2014) Hospitalization burden and survival among older glioblastoma patients. Neuro Oncol 16:1530–1540CrossRefPubMedPubMedCentral Arvold ND, Wang Y, Zigler C, Schrag D, Dominici F (2014) Hospitalization burden and survival among older glioblastoma patients. Neuro Oncol 16:1530–1540CrossRefPubMedPubMedCentral
26.
go back to reference Soussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY (2009) CNS complications of radiotherapy and chemotherapy. Lancet 374:1639–1651CrossRefPubMed Soussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY (2009) CNS complications of radiotherapy and chemotherapy. Lancet 374:1639–1651CrossRefPubMed
27.
go back to reference Wang TJ, Wu CC, Jani A, Estrada J, Ung T, Chow DS, Soun JE, Saad S, Qureshi YH, Gartrell R, Saadatmand HJ, Saraf A, Garrett MD, Grubb C, Isaacson SR, Cheng SK, Sisti MB, Bruce JN, Sheth SA, Lassman AB, Iwamoto FM, McKhann GM (2015) Hypofractionated radiation therapy versus standard fractionated radiation therapy with concurrent temozolomide in elderly patients with newly diagnosed glioblastoma. Pract Radiat Oncol. doi:10.1016/j.prro.2015.12.001 Wang TJ, Wu CC, Jani A, Estrada J, Ung T, Chow DS, Soun JE, Saad S, Qureshi YH, Gartrell R, Saadatmand HJ, Saraf A, Garrett MD, Grubb C, Isaacson SR, Cheng SK, Sisti MB, Bruce JN, Sheth SA, Lassman AB, Iwamoto FM, McKhann GM (2015) Hypofractionated radiation therapy versus standard fractionated radiation therapy with concurrent temozolomide in elderly patients with newly diagnosed glioblastoma. Pract Radiat Oncol. doi:10.​1016/​j.​prro.​2015.​12.​001
28.
go back to reference Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremić B, Rosenblatt E, Fidarova E (2015) International atomic energy agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 33:4145–4150CrossRefPubMed Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremić B, Rosenblatt E, Fidarova E (2015) International atomic energy agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 33:4145–4150CrossRefPubMed
Metadata
Title
Role of irradiation for patients over 80 years old with glioblastoma: a retrospective cohort study
Authors
Stefano Bracci
Florence Laigle-Donadey
Kathryn Hitchcock
Alberto Duran-Peña
Soledad Navarro
Antoine Chevalier
Julian Jacob
Idriss Troussier
Jean-Yves Delattre
Jean-Jacques Mazeron
Khê Hoang-Xuan
Loïc Feuvret
Publication date
01-09-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2182-1

Other articles of this Issue 2/2016

Journal of Neuro-Oncology 2/2016 Go to the issue