Exploring Management and Outcomes of Elderly Patients with Glioblastoma Using Data from Two Randomised Trials (GEINO1401/EX-TEM)

Overview

Journal J Neurooncol

Publisher Springer

Date 2024 Apr 17

PMID 38630385

Authors

Lucy Gately

C Mesia

J M Sepulveda

S Del Barco

E Pineda

R Girones

J Fuster

M Dumas

S Gill

L M Navarro

A Herrero

A Dowling

R de Las Penas

M A Vaz

M Alonso

Z Lwin

R Harrup

S Peralta

A Long

P Perez-Segura

E Ahern

C O Garate

M Wong

R Campbell

K Cuff

R Jennens

O Gallego

C Underhill

M Martinez-Garcia

M Covela

A Cooper

S Brown

M Rosenthal

J Torres

I M Collins

P Gibbs

C Balana

Affiliations

Soon will be listed here.

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.

Citing Articles

Radiotherapeutic advances in the management of glioblastoma.

Gal O, Mehta M, Kotecha R J Neurooncol. 2024; 170(3):509-520.

PMID: 39269554 DOI: 10.1007/s11060-024-04824-x.

References

Ostrom Q, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan J . CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017. Neuro Oncol. 2020; 22(12 Suppl 2):iv1-iv96. PMC: 7596247. DOI: 10.1093/neuonc/noaa200. View

Liu Y, Wasilewski A, Mohile N . Disparities in patient enrollment on glioblastoma clinical trials. CNS Oncol. 2020; 9(2):CNS59. PMC: 7341158. DOI: 10.2217/cns-2020-0008. View

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R . 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(5):459-66. DOI: 10.1016/S1470-2045(09)70025-7. View

Malmstrom A, Gronberg B, Marosi C, Stupp R, Frappaz D, Schultz H . 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. 2012; 13(9):916-26. DOI: 10.1016/S1470-2045(12)70265-6. View

Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M . Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012; 13(7):707-15. DOI: 10.1016/S1470-2045(12)70164-X. View

Perry J, Laperriere N, OCallaghan C, Brandes A, Menten J, Phillips C . Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. N Engl J Med. 2017; 376(11):1027-1037. DOI: 10.1056/NEJMoa1611977. View

Kalra B, Kannan S, Gupta T . Optimal adjuvant therapy in elderly glioblastoma: results from a systematic review and network meta-analysis. J Neurooncol. 2020; 146(2):311-320. DOI: 10.1007/s11060-019-03375-w. View

Balana C, Vaz M, Sepulveda J, Mesia C, Del Barco S, Pineda E . A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01). Neuro Oncol. 2020; 22(12):1851-1861. PMC: 7746946. DOI: 10.1093/neuonc/noaa107. View

10.

Gately L, Mesia C, Sepulveda J, Del Barco S, Pineda E, Girones R . Correction to: 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. 2024; 166(3):417-418. DOI: 10.1007/s11060-024-04581-x. View

11.

Gately L, Collins A, Murphy M, Dowling A . Age alone is not a predictor for survival in glioblastoma. J Neurooncol. 2016; 129(3):479-485. DOI: 10.1007/s11060-016-2194-x. View

12.

Nunna R, Khalid S, Patel S, Sethi A, Behbahani M, Mehta A . Outcomes and Patterns of Care in Elderly Patients with Glioblastoma Multiforme. World Neurosurg. 2021; 149:e1026-e1037. DOI: 10.1016/j.wneu.2021.01.028. View

13.

Al Feghali K, Buszek S, Elhalawani H, Chevli N, Allen P, Chung C . Real-world evaluation of the impact of radiotherapy and chemotherapy in elderly patients with glioblastoma based on age and performance status. Neurooncol Pract. 2021; 8(2):199-208. PMC: 8049423. DOI: 10.1093/nop/npaa064. View

14.

Lorimer C, Hanna C, Saran F, Chalmers A, Brock J . Challenges to Treating Older Glioblastoma Patients: the Influence of Clinical and Tumour Characteristics on Survival Outcomes. Clin Oncol (R Coll Radiol). 2017; 29(11):739-747. DOI: 10.1016/j.clon.2017.05.010. View

15.

Minniti G, Scaringi C, Lanzetta G, Terrenato I, Esposito V, Arcella A . 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. 2014; 91(1):109-15. DOI: 10.1016/j.ijrobp.2014.09.013. View

16.

Arvold N, Tanguturi S, Aizer A, Wen P, Reardon D, Lee E . Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys. 2015; 92(2):384-9. DOI: 10.1016/j.ijrobp.2015.01.017. View

17.

Chang-Halpenny C, Yeh J, Lien W . Elderly patients with glioblastoma multiforme treated with concurrent temozolomide and standard- versus abbreviated-course radiotherapy. Perm J. 2015; 19(1):15-20. PMC: 4315371. DOI: 10.7812/TPP/14-083. View

18.

Gzell C, Wheeler H, Guo L, Kastelan M, Back M . Elderly patients aged 65-75 years with glioblastoma multiforme may benefit from long course radiation therapy with temozolomide. J Neurooncol. 2014; 119(1):187-96. DOI: 10.1007/s11060-014-1472-8. View

19.

Mak K, Agarwal A, Qureshi M, Truong M . Hypofractionated short-course radiotherapy in elderly patients with glioblastoma multiforme: an analysis of the National Cancer Database. Cancer Med. 2017; 6(6):1192-1200. PMC: 5463088. DOI: 10.1002/cam4.1070. View

20.

Wee C, Kim I, Park C, Kim N, Suh C, Chang J . 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. 2020; 148(1):57-65. DOI: 10.1007/s11060-020-03468-x. View