Abstract
Purpose
The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age.
Methods
Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method.
Results
Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0–1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months.
Conclusion
In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data generated in this study are not publicly available as this would compromise patient consent but are available upon reasonable request from the corresponding author.
References
Ostrom QT, Patil N, Cioffi G et al (2020) CBTRUS Statistical Report: primary brain and other central nervous system tumours diagnosed in the United States in 2013–2017. Neuro Oncol 22(12 Suppl 2):iv1–iv96
Liu Y, Wasilewski A, Mohile NA (2020) Disparities in patient enrollment on glioblastoma clinical trials. CNS Oncol 9(2):CNS59
Stupp R, Mason WP, van den Bent MJ, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996
Stupp R, Hegi ME, Mason WP, van den Bent MJ, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group 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(5):459–466
Malmström A, Grønberg BH, 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 13:916–926
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 13:707–715
Perry JR, Laperriere N, O’Callaghan CJ et al (2017) Sort-course radiation plus temozolomide in elderly patients with glioblastoma. NEJM 376:1027–1037
Kalra B, Kannan S, Gupta T (2020) Optimal adjuvant therapy in elderly glioblastoma: results from a systematic review and network meta-analysis. J Neurooncol 146:311–320
Balana C, Vaz MA, Sepúlveda JM et al (2020) A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14– 01). Neuro Oncol 22(12):1851–1861
Gately L, Mesía C, Sepúlveda JM et al (2024) A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma. J Neurooncol 166(3):417–418
Gately L, Collins A, Murphy M, Dowling A (2016) Age alone is not a predictor for survival in glioblastoma. J Neurooncol 129(3):479–485
Nunna RS, Khalid SI, Patel S et al (2021) Outcomes and patterns of care in elderly patients with Glioblastoma multiforme. World Neurosurg 149:e1026–e1037
Al Feghali KA, Buszek SM, Elhalawani H et al (2020) Real-world evaluation of the impact of radiotherapy and chemotherapy in elderly patients with glioblastoma based on age and performance status. Neurooncol Pract 8(2):199–208
Lorimer CF, Hanna C, Saran F et al (2017) Challenges to treating older Glioblastoma patients: the influence of clinical and Tumour characteristics on survival outcomes. Clin Oncol (R Coll Radiol) 29(11):739–747
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(1):109–115
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(2):384–389
Chang-Halpenny CN, Yeh J, Lien WW (2015) Elderly patients with glioblastoma multiforme treated with concurrent temozolomide and standard- versus abbreviated-course radiotherapy. Perm J 19(1):15–20
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 Neurooncol 119(1):187–196
Mak KS, Agarwal A, Qureshi MM, Truong MT (2017) Hypofractionated short-course radiotherapy in elderly patients with glioblastoma multiforme: an analysis of the National Cancer Database. Cancer Med 6(6):1192–1200
Wee CW, Kim IH, Park CK et al (2020) Chemoradiation in elderly patients with glioblastoma from the multi-institutional GBM-molRPA cohort: is short-course radiotherapy enough or is it a matter of selection? J Neurooncol 148:57–65
Internò V, Rudà R, Sergi MC et al (2022) Newly diagnosed Glioblastoma Multiforme (GBM) during COVID-19 pandemic: changes in therapeutic approach to minimize in-hospital SARS-COV-2 contagion in pre-vaccine era. Acta Biomed 93(3):e2022067
Mallick S, Kunhiparambath H, Gupta S et al (2018) Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial). J Neurooncol 140:75–82
Zanello M, Roux A, Ursu R et al (2017) Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment? J Neurooncol 135(2):285–297On the Behalf of the Club de Neuro-Oncologie of the Société Française de Neurochirurgie
Louis DN, Perry A, Wesseling P et al (2021) The 2021 WHO classification of tumors of the Central Nervous System: a summary. Neuro Oncol 23(8):1231–1251
Bruno F, Pellerino A, Palmiero R et al (2022) Glioblastoma in the Elderly: review of Molecular and Therapeutic aspects. Biomedicines 10(3):644
Fukai J, Arita H, Umehara T et al (2020) Molecular characteristics and clinical outcomes of elderly patients with IDH-wildtype glioblastomas: comparative study of older and younger cases in Kansai Network cohort. Brain Tumor Pathol 37:50–59
Li D, Sun C, Kim H et al (2021) Geriatric Assessment–Driven intervention (GAIN) on chemotherapy-related toxic effects in older adults with Cancer: a Randomized Clinical Trial. JAMA Oncol 7(11):e214158
Corre R, Greillier L, Le Caër H et al (2016) Use of a Comprehensive Geriatric Assessment for the management of Elderly patients with Advanced Non-small-cell Lung Cancer: the Phase III Randomized ESOGIA-GFPC-GECP 08– 02 study. J Clin Oncol 34(13):1476–1483
Mohile SG, Mohamed MR, Xu H et al (2021) Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. Lancet 398(10314):1894–1904
Caillet P, Canoui-Poitrine F, Vouriot J et al (2011) Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer: ELCAPA study. J Clin Oncol 29(27):3636–3642
Soo WK, King MT, Pope A et al (2022) Integrated Geriatric Assessment and Treatment Effectiveness (INTEGERATE) in older people with cancer starting systemic anticancer treatment in Australia: a multicentre, open-label, randomised controlled trial. Lancet Healthy Longev 3(9):e617–e627
Monfardini S, Balducci L (1999) A comprehensive geriatric assessment (CGA) is necessary for the study and the management of cancer in the elderly. Eur J Cancer 35:1771–1772
Lorimer CF, Walsh G, MacKinnon M et al (2020) Geriatric assessment of glioblastoma patients is feasible and may provide useful prognostic information. Neurooncol Pract 7(2):176–184
Lombardi G, Bergo E, Caccese M et al (2019) Validation of the comprehensive geriatric assessment as a predictor of mortality in elderly glioblastoma patients. Cancers (Basel) 11:1509–1521
Gately L, Drummond K, Rosenthal M et al (2022) Beyond standard data collection - the promise and potential of BRAIN (brain tumour Registry Australia INnovation and translation registry). BMC Cancer 22(1):604
Funding
The studies were supported financially by the Victoria Comprehensive Cancer Centre (EX-TEM) and a grant from the Spanish Institute Carlos III (ISCIII: PI13/01751 to Carmen Balana) (GEINO14-01). Analysis and manuscript preparation was made possible in part through the authors’ membership of the Brain Cancer Centre.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design as well as data collection. Material preparation and analysis were performed by LG. The first draft of the manuscript was written by LG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Informed consent
Informed consent was obtained from all individual participants included in the studies.
Conflict of interest
The authors declare no potential conflicts of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Gately, L., Mesía, C., Sepúlveda, J. et al. Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM). J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04668-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11060-024-04668-5