Skip to main content
Top
Published in: Journal of Neuro-Oncology 2/2017

01-01-2017 | Clinical Study

Comparative effectiveness of radiotherapy with vs. without temozolomide in older patients with glioblastoma

Authors: Nils D. Arvold, Matthew Cefalu, Yun Wang, Corwin Zigler, Deborah Schrag, Francesca Dominici

Published in: Journal of Neuro-Oncology | Issue 2/2017

Login to get access

Abstract

It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2009, or from 1995 to 1999 before TMZ was available. Three cohorts were assembled based on diagnosis year and treatment initiated within 60 days of diagnosis: (1) 2005–2009 and TMZ/RT, (2) 2005–2009 and RT only, or (3) 1995–1999 and RT only. Associations with OS were estimated using Cox proportional hazards models and propensity score analyses; OS was calculated starting 60 days after diagnosis. Pre-specified sensitivity analyses were performed among patients who received long-course RT (≥27 fractions). Median survival estimates were 7.4 (IQR, 3.3–14.7) months for TMZ/RT, 5.9 (IQR, 2.6–12.1) months for RT alone in 2005–2009, and 5.6 (IQR, 2.7–9.6) months for RT alone in 1995–1999. OS at 2 years was 10.1 % for TMZ/RT, 7.1 % for RT in 2005–2009, and 4.7 % for RT in 1995–1999. Adjusted models suggested decreased mortality risk for TMZ/RT compared to RT in 2005–2009 (AHR, 0.86; 95 % CI, 0.76–0.98) and RT in 1995–1999 (AHR, 0.71; 95 % CI, 0.57–0.90). Among patients from 2005 to 2009 who received long-course RT, however, the addition of TMZ did not significantly improve survival (AHR, 0.91; 95 % CI, 0.80–1.04). In summary, among a large cohort of older glioblastoma patients treated in a real-world setting, the addition of TMZ to RT was associated with a small survival gain.
Literature
1.
go back to reference Wrensch M, Minn Y, Chew T et al (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4:278–299PubMedPubMedCentral Wrensch M, Minn Y, Chew T et al (2002) Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4:278–299PubMedPubMedCentral
2.
go back to reference Walker MD, Green SB, Byar DP et al (1980) Randomized comparisons of raditherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303:1323–1329CrossRefPubMed Walker MD, Green SB, Byar DP et al (1980) Randomized comparisons of raditherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303:1323–1329CrossRefPubMed
3.
go back to reference Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018CrossRefPubMed Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018CrossRefPubMed
4.
go back to reference Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed
5.
go back to reference Malmström A, Gronberg BG, Marosi C et al (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, Gronberg BG, Marosi C et al (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
6.
go back to reference Wick W, Platten M, Meisner C et al (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 et al (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
7.
go back to reference 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 22:1583–1588CrossRefPubMed 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 22:1583–1588CrossRefPubMed
8.
go back to reference Gállego Pérez-Larraya J, Ducray F, Chinot O et al (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol 29:2050–2055 Gállego Pérez-Larraya J, Ducray F, Chinot O et al (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol 29:2050–2055
9.
go back to reference Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed
10.
go back to reference Perry JR, Laperriere N, O’Callaghan CJ et al (2016) A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677). J Clin Oncol 34(18_suppl):p LBA2 Perry JR, Laperriere N, O’Callaghan CJ et al (2016) A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677). J Clin Oncol 34(18_suppl):p LBA2
11.
go back to reference Chakrabarti I, Cockburn M, Cozen W et al (2005) A population-based description of glioblastoma multiforme in Los Angeles County, 1974–1999. Cancer 104:2798–2806CrossRefPubMed Chakrabarti I, Cockburn M, Cozen W et al (2005) A population-based description of glioblastoma multiforme in Los Angeles County, 1974–1999. Cancer 104:2798–2806CrossRefPubMed
13.
go back to reference Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619CrossRefPubMed Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619CrossRefPubMed
14.
go back to reference Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMed Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMed
15.
go back to reference Cohen MH, Johnson JR, Pazdur R (2005) Food and drug administration drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Clin Cancer Res 11:6767–6771CrossRefPubMed Cohen MH, Johnson JR, Pazdur R (2005) Food and drug administration drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Clin Cancer Res 11:6767–6771CrossRefPubMed
16.
go back to reference Darefsky AS, King JT Jr, Dubrow R (2012) Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of surveillance, epidemiology, and end results registries. Cancer 118:2163–2172CrossRefPubMed Darefsky AS, King JT Jr, Dubrow R (2012) Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of surveillance, epidemiology, and end results registries. Cancer 118:2163–2172CrossRefPubMed
17.
go back to reference Park HS, Gross CP, Makarov DV et al (2012) Immortal time bias: a frequently unrecognized threat to the validity in the evaluation of postoperative radiotherapy. Int J Radiat Oncol Biol Phys 83:1365–1373CrossRefPubMed Park HS, Gross CP, Makarov DV et al (2012) Immortal time bias: a frequently unrecognized threat to the validity in the evaluation of postoperative radiotherapy. Int J Radiat Oncol Biol Phys 83:1365–1373CrossRefPubMed
18.
go back to reference Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55CrossRef Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55CrossRef
19.
go back to reference D’Agostino RB Jr, D’Agostino RB Sr (2007) Estimating treatment effects using observational data. JAMA 297:314–316CrossRefPubMed D’Agostino RB Jr, D’Agostino RB Sr (2007) Estimating treatment effects using observational data. JAMA 297:314–316CrossRefPubMed
20.
go back to reference Rubin DB (1997) Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127:757–763CrossRefPubMed Rubin DB (1997) Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127:757–763CrossRefPubMed
21.
go back to reference D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281CrossRefPubMed D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281CrossRefPubMed
22.
go back to reference Lunceford JK, Davidian M (2004) Stratification and weighting via the propensity score in estimation of causal treatment effects: a comparative study. Stat Med 23:2937–2960CrossRefPubMed Lunceford JK, Davidian M (2004) Stratification and weighting via the propensity score in estimation of causal treatment effects: a comparative study. Stat Med 23:2937–2960CrossRefPubMed
23.
go back to reference Zhu J, Sharma DB, Gray SW et al (2012) Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 307:1593–1601CrossRefPubMedPubMedCentral Zhu J, Sharma DB, Gray SW et al (2012) Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 307:1593–1601CrossRefPubMedPubMedCentral
24.
go back to reference Arvold ND, Reardon DA (2014) Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging 9:357–367PubMedPubMedCentral Arvold ND, Reardon DA (2014) Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging 9:357–367PubMedPubMedCentral
25.
26.
go back to reference Stupp R, Hegi ME, Mason WP et al (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 et al (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
27.
go back to reference Laperriere N, Weller M, Stupp R et al (2013) Optimal management of elderly patients with glioblastoma. Cancer Treat Rev 39:350–357CrossRefPubMed Laperriere N, Weller M, Stupp R et al (2013) Optimal management of elderly patients with glioblastoma. Cancer Treat Rev 39:350–357CrossRefPubMed
28.
go back to reference Iwamoto FM, Reiner AS, Panageas KS et al (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628–634CrossRefPubMed Iwamoto FM, Reiner AS, Panageas KS et al (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628–634CrossRefPubMed
30.
go back to reference 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 115:3512–3518CrossRefPubMed 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 115:3512–3518CrossRefPubMed
31.
go back to reference Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97–103CrossRefPubMed Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97–103CrossRefPubMed
32.
go back to reference Arvold ND, Tanguturi SK, Aizer AA et al (2015) Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92:382–389CrossRef Arvold ND, Tanguturi SK, Aizer AA et al (2015) Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92:382–389CrossRef
33.
go back to reference Minniti G, Scaringi C, Lanzetta G et al (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 91:109–115CrossRefPubMed Minniti G, Scaringi C, Lanzetta G et al (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 91:109–115CrossRefPubMed
34.
go back to reference Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed
35.
go back to reference Weller M, van den Bent M, Hopkins K et al (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15:e395–e403CrossRefPubMed Weller M, van den Bent M, Hopkins K et al (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15:e395–e403CrossRefPubMed
36.
go back to reference Wick W, Weller M, van den Bent M et al (2014) MGMT testing–the challenges for biomarker-based glioma treatment. Nat. Rev Neurol 10:372–385CrossRef Wick W, Weller M, van den Bent M et al (2014) MGMT testing–the challenges for biomarker-based glioma treatment. Nat. Rev Neurol 10:372–385CrossRef
37.
go back to reference Weller M, Stupp R, Hegi ME et al (2012) Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice. Neuro Oncol 14:iv100–108PubMedPubMedCentral Weller M, Stupp R, Hegi ME et al (2012) Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice. Neuro Oncol 14:iv100–108PubMedPubMedCentral
38.
go back to reference Davidoff AJ, Shaffer T, Erten MZ et al (2013) Use and spending on antineoplastic therapy for medicare beneficiaries with cancer. Med Care 51:351–360CrossRefPubMed Davidoff AJ, Shaffer T, Erten MZ et al (2013) Use and spending on antineoplastic therapy for medicare beneficiaries with cancer. Med Care 51:351–360CrossRefPubMed
39.
go back to reference Ray S, Bonafede MM, Mohile NA (2014) Treatment patterns, survival, and healthcare costs of patients with malignant gliomas in a large US commercially insured population. Am Health Drug Benefits 7:140–149PubMedPubMedCentral Ray S, Bonafede MM, Mohile NA (2014) Treatment patterns, survival, and healthcare costs of patients with malignant gliomas in a large US commercially insured population. Am Health Drug Benefits 7:140–149PubMedPubMedCentral
40.
go back to reference Cohen MH, Shen YL, Keegan P et al (2009) FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 14:1131–1138CrossRefPubMed Cohen MH, Shen YL, Keegan P et al (2009) FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 14:1131–1138CrossRefPubMed
Metadata
Title
Comparative effectiveness of radiotherapy with vs. without temozolomide in older patients with glioblastoma
Authors
Nils D. Arvold
Matthew Cefalu
Yun Wang
Corwin Zigler
Deborah Schrag
Francesca Dominici
Publication date
01-01-2017
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2294-7

Other articles of this Issue 2/2017

Journal of Neuro-Oncology 2/2017 Go to the issue