O-(2-[18F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial

Grosu AL, Weber WA, Graf E, Mix M, Nestle U, Schimek-Jasch T, Wiehle R, Mader I, Würtemberger U, Langen KJ, Niyazi M, Paulsen F, König L, Giordano FA, Spehl I, Bernhardt D, Schymalla MM, Pöttgen C, Semrau S, Brunner T, Hültenschmidt B, Krause BJ, Ciernik IF, Beck J, Baumert BG, Meyer PT, Urbach H, Popp I, Belka C, Eckert F, Eble MJ, Sperk E, Momm F, Combs SE, Wiestler B, Engenhart-Cabillic R, Stuschke M, Fietkau R, Nadji S, Hildebrandt G, Chakravarti A, Short SC, Nieder C, Schneider-Fuchs S, Prinz M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 27

Pages Range: 169-180

Journal Issue: 2

DOI: 10.1016/S1470-2045(25)00642-4

Abstract

Background O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET)-PET has a higher specificity than contrast-enhanced T1-weighted MRI (CE-T1MRI) in diagnosing recurrent glioblastoma. We aimed to evaluate whether a FET-PET-based target volume delineation, compared with CE-T1MRI, improves outcomes in patients with recurrent glioblastoma scheduled for re-irradiation. Methods GLIAA was a multicentre, open-label, parallel randomised study done in 15 radiation oncology centres in Germany. Patients aged 18 years or older with a Karnofsky performance score greater than 60% and a macroscopic WHO grade IV recurrent glioblastoma (1–6 cm) were randomly assigned (1:1) to receive either FET-PET-based or CE-T1MRI-based target volume delineation followed by re-irradiation with 39 Gy in 13 fractions. Randomisation was performed centrally, using a minimisation technique with a random element and a computer-assisted randomisation tool, stratified by time since first radiotherapy, previous chemotherapy, tumour diameter, MGMT status, and planned chemotherapy. The primary endpoint was progression-free survival from randomisation, assessed in the per-protocol population (patients who initiated treatment per their assigned group). Adverse events were systematically assessed in all patients who commenced therapy. The trial was registered with ClinicalTrials.gov ( NCT01252459 ), German Clinical Trials Registry (DRKS00000634), and European Clinical Trials Database (EudraCT 2012–001121–27), and is completed. Findings Between Nov 22, 2013, and Aug 18, 2021, 271 patients were recruited and screened for eligibility, 200 of whom were randomly assigned to re-irradiation based on FET-PET (n=100) or CE-T1MRI (n=100). 85 (43%) participants were female and 115 (58%) were male. 98 patients in the FET-PET group and 97 in the CE-T1MRI group were treated per protocol. Median follow-up for censored patients was 12·2 months (IQR 6·6-20·7). Median progression-free survival was 4·0 months (95% CI 3·7–5·2) in the FET-PET group and 4·9 months (3·7–6·0) in the CE-T1MRI group (one-sided stratified log-rank p=0·98; adjusted hazard ratio 1·14 [95% CI 0·85–1·52]; p=0·39; median follow-up for six censored patients 4·1 months [IQR 2·3–6·6]). The most common grade 3–4 adverse event was radionecrosis (eight [8%] of 99 in the FET-PET group vs seven [7%] of 99 in the CE-T1MRI group). Acute and subacute serious adverse events occurred in 15 (15%) of 99 patients in each group; possibly re-irradiation-related late serious adverse events occurred in ten (10%) of 97 patients in the FET-PET group and 18 (19%) of 96 in the CE-T1MRI group. There were no treatment-related deaths. Interpretation FET-PET-based target volume delineation for re-irradiation did not lead to a significant clinical benefit compared with CE-T1MRI-based treatment in patients with recurrent glioblastoma. Thus, CE-T1MRI remains the preferred delineation method in this setting. Funding Deutsche Krebshilfe.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Freiburg Germany (DE) Technische Universität München (TUM) Germany (DE) Philipps-Universität Marburg Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Kantonsspital Graubünden Switzerland (CH) Städtisches Klinikum Dessau Germany (DE) Forschungszentrum Jülich / Research Centre Jülich (FZJ) Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Klinikum rechts der Isar Germany (DE) Universitätsmedizin Rostock Germany (DE)

How to cite

APA:

Grosu, A.L., Weber, W.A., Graf, E., Mix, M., Nestle, U., Schimek-Jasch, T.,... Prinz, M. (2026). O-(2-[18F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial. Lancet Oncology, 27(2), 169-180. https://doi.org/10.1016/S1470-2045(25)00642-4

MLA:

Grosu, Anca Ligia, et al. "O-(2-[18F]fluoroethyl)-L-tyrosine-PET-guided versus contrast-enhanced T1-weighted MRI-guided re-irradiation in patients with recurrent glioblastoma (GLIAA/NOA-10 ARO2013-01): a multicentre, open-label, randomised trial." Lancet Oncology 27.2 (2026): 169-180.

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