Skip to main content
Erschienen in: Journal of Neuro-Oncology 1/2017

19.05.2017 | Clinical Study

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival

verfasst von: Scott M. Glaser, Michael J. Dohopolski, Goundappa K. Balasubramani, John C. Flickinger, Sushil Beriwal

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65–90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54–65 Gy at 1.7–2.1 Gy/fraction) to HFRT (34–60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p < 0.0005 by log-rank, multivariable HR 0.65 [95% CI = 0.61–0.68, p < 0.0005], multivariable HR with propensity adjustment 0.66 [95% CI = 0.63–0.70, p < 0.0005]). For elderly GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Ostrom Q, Gittleman H, Fulop J et al (2015) CBTRUS Statistical Report: Primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncology 17(suppl 4):iv1–iv62CrossRef Ostrom Q, Gittleman H, Fulop J et al (2015) CBTRUS Statistical Report: Primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncology 17(suppl 4):iv1–iv62CrossRef
2.
Zurück zum Zitat Stupp R, Mason W, van den Bent M et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed Stupp R, Mason W, van den Bent M et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed
3.
Zurück zum Zitat Stupp R, Hegi M, Mason W 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 M, Mason W 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
4.
Zurück zum Zitat Brandes A, Franceschi E (2011) Primary brain tumors in the elderly population. Curr Treat Options Neurol 13:427–435CrossRefPubMed Brandes A, Franceschi E (2011) Primary brain tumors in the elderly population. Curr Treat Options Neurol 13:427–435CrossRefPubMed
5.
Zurück zum Zitat Farina P, Lombardi G, Bergo E et al (2014) Treatment of malignant gliomas in elderly patients: a concise overview of the literature. Biomed Res Int 2014:734281CrossRefPubMedPubMedCentral Farina P, Lombardi G, Bergo E et al (2014) Treatment of malignant gliomas in elderly patients: a concise overview of the literature. Biomed Res Int 2014:734281CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Jordan J, Gerstner E, Batchelor T et al (2016) Glioblastoma care in the elderly. Cancer 122:189–197CrossRefPubMed Jordan J, Gerstner E, Batchelor T et al (2016) Glioblastoma care in the elderly. Cancer 122:189–197CrossRefPubMed
7.
Zurück zum Zitat Roa W, Brasher P, 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 P, 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.
Zurück zum Zitat 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
9.
Zurück zum Zitat Roa W, Kepka L, Kumar N et al (2015) International Atomic Engery 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 et al (2015) International Atomic Engery 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
10.
Zurück zum Zitat Malmström A, Grønberg B, Marosi C et al (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomized, phase 3 trial. Lancet Oncol 13:916–926CrossRefPubMed Malmström A, Grønberg B, Marosi C et al (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomized, phase 3 trial. Lancet Oncol 13:916–926CrossRefPubMed
11.
Zurück zum Zitat Wick W, Platten M, Meisner C et al (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocystoma 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 astrocystoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715CrossRefPubMed
12.
Zurück zum Zitat Perry J, Laperriere N, O’Callaghan C et al (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376:1027–1037CrossRefPubMed Perry J, Laperriere N, O’Callaghan C et al (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376:1027–1037CrossRefPubMed
13.
Zurück zum Zitat Franceschi E, Depenni R, Paccapelo A et al (2016) Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study. J Neurooncol 128:157–162CrossRefPubMed Franceschi E, Depenni R, Paccapelo A et al (2016) Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study. J Neurooncol 128:157–162CrossRefPubMed
14.
Zurück zum Zitat Lombardi G, Pace A, Pasqualetti F et al (2015) Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology). J Neurooncol 125:359–367CrossRefPubMed Lombardi G, Pace A, Pasqualetti F et al (2015) Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology). J Neurooncol 125:359–367CrossRefPubMed
15.
Zurück zum Zitat Brandes A, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma. Cancer 115:3512–3518CrossRefPubMed Brandes A, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma. Cancer 115:3512–3518CrossRefPubMed
16.
Zurück zum Zitat 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
17.
Zurück zum Zitat Arvold N, Tanguturi S, Aizer A et al (2015) Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92:384–389CrossRefPubMed Arvold N, Tanguturi S, Aizer A et al (2015) Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92:384–389CrossRefPubMed
18.
Zurück zum Zitat Minniti G, De Sanctis V, Muni R (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91:95–100CrossRefPubMed Minniti G, De Sanctis V, Muni R (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91:95–100CrossRefPubMed
19.
Zurück zum Zitat Reyngold M, Lassman A, Chan T et al (2012) Abbreviated course of radiation therapy with concurrent temozolomide for high-grade glioma in patients of advanced age or poor functional status. J Neurooncol 110:369–374CrossRefPubMed Reyngold M, Lassman A, Chan T et al (2012) Abbreviated course of radiation therapy with concurrent temozolomide for high-grade glioma in patients of advanced age or poor functional status. J Neurooncol 110:369–374CrossRefPubMed
20.
Zurück zum Zitat Minniti G, Lanzetta G, Scaringi C et al (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 et al (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
21.
Zurück zum Zitat Gzell C, Wheeler H, Guo L et al (2014) Elderly patients aged 65–75 years with glioblastoma multiforme may benefit from long course radiation therapy with temozolomide. J Neruooncol 119:187–196CrossRef Gzell C, Wheeler H, Guo L et al (2014) Elderly patients aged 65–75 years with glioblastoma multiforme may benefit from long course radiation therapy with temozolomide. J Neruooncol 119:187–196CrossRef
22.
Zurück zum Zitat Bilimoria K, Stewart A, Winchester D, Ko C (2008) The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 15:683–690CrossRefPubMedPubMedCentral Bilimoria K, Stewart A, Winchester D, Ko C (2008) The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 15:683–690CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Bilimoria K, Bentrem D, Stewart A et al (2009) Comparison of commission on cancer-approved and -nonapproved hospitals in the United States: implications for studies that use the National Cancer Data Base. J Clin Oncol 27:4177–4181CrossRefPubMed Bilimoria K, Bentrem D, Stewart A et al (2009) Comparison of commission on cancer-approved and -nonapproved hospitals in the United States: implications for studies that use the National Cancer Data Base. J Clin Oncol 27:4177–4181CrossRefPubMed
24.
Zurück zum Zitat Charlson M, Pompei P, Ales K, MacKenzie C (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMed Charlson M, Pompei P, Ales K, MacKenzie C (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMed
25.
Zurück zum Zitat Deyo R, Cherkin D, Ciol M (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619CrossRefPubMed Deyo R, Cherkin D, Ciol M (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619CrossRefPubMed
26.
Zurück zum Zitat D’Agostino R (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 R (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281CrossRefPubMed
27.
Zurück zum Zitat Vargo J, Gill B, Balasubramani G, Beriwal S (2015) Treatment selection and survival outcomes in early-stage diffuse large B-cell lymphoma: do we still need consolidative radiotherapy? J Clin Oncol 33:3710–3717CrossRefPubMed Vargo J, Gill B, Balasubramani G, Beriwal S (2015) Treatment selection and survival outcomes in early-stage diffuse large B-cell lymphoma: do we still need consolidative radiotherapy? J Clin Oncol 33:3710–3717CrossRefPubMed
28.
Zurück zum Zitat Olszewski A, Shrestha R, Castillo J (2015) Treatment selection and outcomes in early-stage classical Hodgkin lymphoma: analysis of the national cancer data base. J Clin Oncol 33:625–633CrossRefPubMed Olszewski A, Shrestha R, Castillo J (2015) Treatment selection and outcomes in early-stage classical Hodgkin lymphoma: analysis of the national cancer data base. J Clin Oncol 33:625–633CrossRefPubMed
29.
Zurück zum Zitat Buckner J (2003) Factors influencing survival in high-grade gliomas. Semin Oncol 30(Suppl 19):10–14CrossRefPubMed Buckner J (2003) Factors influencing survival in high-grade gliomas. Semin Oncol 30(Suppl 19):10–14CrossRefPubMed
30.
Zurück zum Zitat Curran W, Scott C, Horton J et al (1993) Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85:704–710CrossRefPubMed Curran W, Scott C, Horton J et al (1993) Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85:704–710CrossRefPubMed
31.
Zurück zum Zitat Gorila T, van den Bent M, Hegi M et al (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 9:29–38CrossRef Gorila T, van den Bent M, Hegi M et al (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 9:29–38CrossRef
32.
Zurück zum Zitat Mirimanoff R, Gorila 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 Oncolo 24:2563–2569CrossRef Mirimanoff R, Gorila 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 Oncolo 24:2563–2569CrossRef
33.
Zurück zum Zitat Li J, Wang M, Won M et al (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncolo Biol Phys 81:623–630CrossRef Li J, Wang M, Won M et al (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncolo Biol Phys 81:623–630CrossRef
34.
Zurück zum Zitat Pignatti F, van den Bent M, Curran D et al (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084CrossRefPubMed Pignatti F, van den Bent M, Curran D et al (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084CrossRefPubMed
35.
Zurück zum Zitat Sijben A, McIntyre J, Roldán G et al (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89:97–103CrossRefPubMed Sijben A, McIntyre J, Roldán G et al (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89:97–103CrossRefPubMed
36.
Zurück zum Zitat Hegi M, Diserens A, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed Hegi M, Diserens A, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed
37.
Zurück zum Zitat Sandmann T, Bourgon R, Garcia J et al (2015) Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: retrospective analysis of the AVAglio trial. J Clin Oncol 33:2734–2744CrossRef Sandmann T, Bourgon R, Garcia J et al (2015) Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: retrospective analysis of the AVAglio trial. J Clin Oncol 33:2734–2744CrossRef
38.
Zurück zum Zitat Gerstner E, Yip S, Wang D et al (2009) MGMT methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 73:1509–1510CrossRefPubMedPubMedCentral Gerstner E, Yip S, Wang D et al (2009) MGMT methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma. Neurology 73:1509–1510CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Stupp R, Taillibert S, Kanner A et al (2015) Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma a randomized clinical trial. JAMA 314:2535–2543CrossRefPubMed Stupp R, Taillibert S, Kanner A et al (2015) Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma a randomized clinical trial. JAMA 314:2535–2543CrossRefPubMed
40.
Zurück zum Zitat Cao J, Fisher B, Bauman G et al (2012) Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience. J Neurooncol 107:395–405CrossRefPubMed Cao J, Fisher B, Bauman G et al (2012) Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience. J Neurooncol 107:395–405CrossRefPubMed
Metadaten
Titel
Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival
verfasst von
Scott M. Glaser
Michael J. Dohopolski
Goundappa K. Balasubramani
John C. Flickinger
Sushil Beriwal
Publikationsdatum
19.05.2017
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2017
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2493-x

Weitere Artikel der Ausgabe 1/2017

Journal of Neuro-Oncology 1/2017 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Neu im Fachgebiet Neurologie

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.