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. 2024 Dec 4;6(1):vdae211.
doi: 10.1093/noajnl/vdae211. eCollection 2024 Jan-Dec.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial

Annika Malmström  1 , Felix B Oppong  2 , Christopher J O Callaghan  3 , Wolfgang Wick  4 , Normand Laperriere  5 , Thierry Gorlia  2 , Michael Weller  6 , Roger Henriksson  7 , Warren Mason  8 , Michael Platten  9 , Eva Cantagallo  10 , Bjørn H Grønberg  11 , Guido Reifenberger  12 , Christine Marosi  13 , James R Perry  14 ; NCBTSG, NOA, CCTG and EORTC Brain Tumor Group
Collaborators, Affiliations

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial

Annika Malmström et al. Neurooncol Adv. .

Abstract

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.6 randomized between hypofractionated RT and RT + TMZ. All showed significant benefits for the TMZ arms, especially for those patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. This pooled analysis aimed at identifying additional factors that could improve individualized treatment recommendations.

Methods: Analyses were performed separately in the RT and TMZ arms of the pooled NORDIC and NOA-08 data, and in the RT and TMZ/RT arms of CE.6. The prognostic value of baseline clinical factors, comorbidities, and quality of life (QoL) scores were assessed.

Results: NORDIC + NOA-08 (NN) included 715 patients and CE.6 included 562 patients. Median age for NN was 71 and 73 years for CE.6. In NN and CE.6 respectively, 66.2% versus 70.5% underwent resection and 50.9% and 75.3% were on steroids. In NN, 401 patients received RT alone and 281 in CE.6, while 314 were randomized to TMZ alone in NN and 281 to concomitant RT + TMZ in CE.6. Known clinical prognostic factors, such as extent of resection and WHO performance status were confirmed, as was MGMT promoter methylation status for TMZ-treated patients. TMZ-treated patients with 2 or 3 comorbidities; hypertension, diabetes, and/or stroke had worse survival, both in NN (P = .022) and CE.6 (P = .022). Baseline QoL had a minor association with outcome.

Conclusion: Consideration of comorbidities allows improved personalized treatment decisions for elderly glioblastoma patients.

Keywords: comorbidities; elderly glioblastoma patients; pooled analysis; prognostic factors.

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Conflict of interest statement

A.M., F.B.O., C.O.C., N.L., T.G., E.C., G.R., C.M., and J.P. none. M.W. has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche, and Servier. R.H. has since the start of the Nordic study received honoraria for lectures or advisory board participation or consulting from Novocure, MSD, Roche, Astra Zeneca, and BrainCool. W.W. Honoraria for consultation or non-financial clinical trial support from Apogenix, Bayer, Merck Sharp & Dome, AstraZeneca, Merck Serono, Novartis, Roche and Mundipharma, with compensation paid to the Medical Faculty at Heidelberg University. B.H.G. research funding from AstraZeneca and Roche, and honoraria from MSD, AstraZeneca, Pfizer, Janssen, Sanofi, Takeda, Eli Lilly, BMS, Gilead and Debiopharm. W.M. consultant for Merck, Servier, Novocure, Boehringer Ingelheim, and chairs a data monitoring committee for Ono Therapeutics. M.P. has received research grants and support from Bayer, Merck, Pfizer and Roche, and advisory board participation compensation from Cellula Therapeutics.

Figures

Figure 1.
Figure 1.
Association of number of the comorbidities DT, HT, and/or CVI with OS by treatment arm for each trial. Kaplan–Meier survival curve of overall survival in patients with 0–1 comorbidity versus 2 or more comorbidities for each trial and treatment combination. (A) Nordic TMZ arm, (B) Nordic RT arm, (C) CE.6 RT/TMZ arm, and (D) CE.6 RT arm. Significant OS differences were observed in the RT arm of CE.6, and in the TMZ arms of both the Nordic and CE.6.
Figure 1.
Figure 1.
Association of number of the comorbidities DT, HT, and/or CVI with OS by treatment arm for each trial. Kaplan–Meier survival curve of overall survival in patients with 0–1 comorbidity versus 2 or more comorbidities for each trial and treatment combination. (A) Nordic TMZ arm, (B) Nordic RT arm, (C) CE.6 RT/TMZ arm, and (D) CE.6 RT arm. Significant OS differences were observed in the RT arm of CE.6, and in the TMZ arms of both the Nordic and CE.6.
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