Feasibility of a reduced gadolinium dose protocol for MRI-guided radiotherapy in glioblastoma

Authors

  • Faisal Mahmood Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Department of Clinical Research, Odense, Denmark https://orcid.org/0000-0002-7270-7967
  • Uffe Bernchou Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Department of Clinical Research, Odense, Denmark https://orcid.org/0000-0002-5309-2696
  • Severin Gråe Department of Radiology, Odense University Hospital, Odense, Denmark
  • Anders Smedegaard Bertelsen Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0003-0022-0786
  • Anne Bisgaard Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-5402-0045
  • Rasmus Lübeck Christiansen Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0003-3254-5075
  • Bahar Celik Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark
  • Elisabeth Kildegaard Laboratory of Radiation Physics, Department of Oncology, Odense University Hospital, Odense, Denmark
  • Tine Schytte University of Southern Denmark, Department of Clinical Research, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0002-6705-1561
  • Rikke Hedegaard Dahlrot University of Southern Denmark, Department of Clinical Research, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark https://orcid.org/0000-0003-1538-4361

DOI:

https://doi.org/10.2340/1651-226X.2025.44022

Keywords:

Magnetic resonance imaging, contrast media, radiotherapy, Caregiver glioblastoma group intervention high-grade glioma neuro-oncology

Abstract

Background and purpose: Magnetic resonance imaging-guided radiotherapy (MRIgRT) enables precise tumour targeting through adaptive planning, which is particularly relevant for glioblastoma due to its dynamic morphology. Gadolinium-based contrast agents (GBCAs) enhance tumour visibility, but frequent use during MRIgRT raises safety concerns related to cumulative gadolinium exposure. This study investigated the feasibility of a reduced GBCA dose protocol for patients with glioblastoma undergoing MRIgRT, aiming to balance tumour conspicuity with minimisation of GBCA-related risks.

Patient/material and methods: Nine patients with glioblastoma received hypo-fractionated MRI-Linac radiotherapy (10 × 3.4 Gy) with MRI performed with either full-dose, half-dose or no GBCA enhancement. Online gross tumour volume (GTV) delineation was performed by radiation oncologists, while offline GTV delineation was independently conducted by an expert neuroradiologist on GBCA-enhanced scans. Objective assessment using automatic thresholding and a structured Likert-scale evaluation were also performed.

Results: During online adaptation, GTV volumes generally remained stable or increased, whereas offline expert assessments revealed a general volume reduction and systematic volume underestimation with half-dose scans (~18%). Relative delineation volume discrepancies were most pronounced in small tumours. Structured radiologist feedback reported lower confidence, tumour conspicuity and image quality in half-dose scans, particularly for small lesions. Otsu’s thresholding revealed reduced edge definition with decreasing contrast dose. No signs of GBCA retention were observed between fractions.

Interpretation: Reduced-dose GBCA-protocols are feasible. Full-dose contrast is recommended at key fractions (e.g. baseline and mid-treatment) and for small tumours, with half-dose imaging reserved for selected intervals or larger tumours. This hybrid approach may balance safety and imaging precision in adaptive MRIgRT.

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References

Raaymakers BW, Jürgenliemk-Schulz IM, Bol GH, Glitzner M, Kotte ANTJ, Van Asselen B, et al. First patients treated with a 1.5 T MRI-Linac: Clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment. Phys Med Biol. 2017;62(23):L41–50.

https://doi.org/10.1088/1361-6560/aa9517 DOI: https://doi.org/10.1088/1361-6560/aa9517

Weinmann HJ, Brasch RC, Press WR, Wesbey GE. Characteristics of gadolinium-DTPA complex: A potential NMR contrast agent. Am J Roentgenol. 1984;142(3):619–24.

https://doi.org/10.2214/ajr.142.3.619 DOI: https://doi.org/10.2214/ajr.142.3.619

Wu Z, Dai L, Tang K, Ma Y, Song B, Zhang Y, et al. Advances in magnetic resonance imaging contrast agents for glioblastoma-targeting theranostics. Regen Biomater. 2021;8(6):rbab062.

https://doi.org/10.1093/rb/rbab062 DOI: https://doi.org/10.1093/rb/rbab062

Bernchou U, Skak Tranemose Arnold T, Axelsen B, Klüver-Kristensen M, Mahmood F, Severin Gråe Harbo F, et al. Evolution of the gross tumour volume extent during radiotherapy for glioblastomas. Radiother Oncol. 2021;160:40–46.

https://doi.org/10.1016/j.radonc.2021.04.001 DOI: https://doi.org/10.1016/j.radonc.2021.04.001

Stewart J, Sahgal A, Lee Y, Soliman H, Tseng CL, Detsky J, et al. Quantitating interfraction target dynamics during concurrent chemoradiation for glioblastoma: a prospective serial imaging study. Int J Radiat Oncol Biol Phys. 2020;109(3):736–46.

https://doi.org/10.1016/j.ijrobp.2020.10.002 DOI: https://doi.org/10.1016/j.ijrobp.2020.10.002

Wang J, Salzillo T, Jiang Y, Mackeyev Y, Fuller CD, Chung C, et al. Stability of MRI contrast agents in high-energy radiation of a 1.5T MR-Linac. Radiother Oncol. 2021;161:55–64.

https://doi.org/10.1016/j.radonc.2021.05.023 DOI: https://doi.org/10.1016/j.radonc.2021.05.023

Mahmood F, Nielsen UG, Jørgensen CB, Brink C, Thomsen HS, Hansen RH. Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy – an investigation of chelate stability using relaxometry. Phys Imaging Radiat Oncol. 2022;21:96–100. DOI: https://doi.org/10.1016/j.phro.2022.02.015

https://doi.org/10.1016/j.phro.2022.02.015/

McDonald RJ, Levine D, Weinreb J, Kanal E, Davenport MS, Ellis JH, et al. Gadolinium retention: a research roadmap from the 2018 NIH/ACR/RSNA workshop on gadolinium chelates. Radiology. 2018;289(2):517–534.

https://doi.org/10.1148/radiol.2018181151 DOI: https://doi.org/10.1148/radiol.2018181151

Tweedle MF. Gadolinium retention in human brain, bone, and skin. Radiology [Internet]. 2021 [cited 2021 Jun 18];210957. Available from: http://pubs.rsna.org/doi/10.1148/radiol.2021210957

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Br Med J. 2007;335(7624):806.

https://doi.org/10.1136/bmj.39335.541782.AD DOI: https://doi.org/10.1136/bmj.39335.541782.AD

de Mol van Otterloo SR, Christodouleas JP, Blezer ELA, Akhiat H, Brown K, Choudhury A, et al. The MOMENTUM study: an international registry for the evidence-based introduction of MR-guided adaptive therapy. Front Oncol. 2020;10:1328.

https://doi.org/10.3389/fonc.2020.01328 DOI: https://doi.org/10.3389/fonc.2020.01328

ICRU Report 97, MRI-guided radiation therapy using MRI-linear accelerators – ICRU [Internet]. [cited 2025 May 18]. Available from: https://www.icru.org/report/icru-report-97-mri-guided-radiation-therapy-using-mri-linear-accelerators/

Klein S, Staring M, Murphy K, Viergever MA, Pluim JPW. Elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2010;29(1):196–205.

https://doi.org/10.1109/TMI.2009.2035616 DOI: https://doi.org/10.1109/TMI.2009.2035616

Otsu N. Threshold selection method from Gray-level histograms. IEEE Trans Syst Man Cybern. 1979;SMC-9(1):62–6.

https://doi.org/10.1109/TSMC.1979.4310076 DOI: https://doi.org/10.1109/TSMC.1979.4310076

Oksendal AN, Hals P‐A. Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging. 1993;3(1):157–65.

https://doi.org/10.1002/jmri.1880030128 DOI: https://doi.org/10.1002/jmri.1880030128

Gutierrez JE, Rosenberg M, Seemann J, Breuer J, Haverstock D, Agris J, et al. Safety and efficacy of gadobutrol for contrast-enhanced magnetic resonance imaging of the central nervous system: results from a multicenter, double-blind, randomized, comparator study. Magn Reson Insights. 2015;8:MRI.S19794.

https://doi.org/10.4137/MRI.S19794 DOI: https://doi.org/10.4137/MRI.S19794

Lewis D, Li KL, Waqar M, Coope DJ, Pathmanaban ON, King AT, et al. Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study. Sci Rep [Internet]. 2024 [cited 2025 May 18];14(1):1–14. Available from: https://www.nature.com/articles/s41598-024-53871-x DOI: https://doi.org/10.1038/s41598-024-53871-x

Loevner LA, Kolumban B, Hutóczki G, Dziadziuszko K, Bereczki D, Bago A, et al. Efficacy and safety of gadopiclenol for contrast-enhanced MRI of the central nervous system: The PICTURE randomized clinical trial. Invest Radiol. 2023;58(5):307–13.

https://doi.org/10.1097/RLI.0000000000000944 DOI: https://doi.org/10.1097/RLI.0000000000000944

Gong E, Pauly JM, Wintermark M, Zaharchuk G. Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI. J Magn Reson Imaging. 2018;48(2):330–40. DOI: https://doi.org/10.1002/jmri.25970

https://doi.org/

Moya-Sáez E, de Luis-García R, Alberola-López C. Toward deep learning replacement of gadolinium in neuro-oncology: a review of contrast-enhanced synthetic MRI. Front Neuroimaging. 2023;2:1055463.

https://doi.org/10.3389/fnimg.2023.1055463 DOI: https://doi.org/10.3389/fnimg.2023.1055463

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Published

2025-09-10

How to Cite

Mahmood, F., Bernchou, U., Harboe, F. S. G., Bertelsen, A. S., Bisgaard, A., Lübeck Christiansen, R., … Hedegaard Dahlrot, R. (2025). Feasibility of a reduced gadolinium dose protocol for MRI-guided radiotherapy in glioblastoma. Acta Oncologica, 64, 1185–1193. https://doi.org/10.2340/1651-226X.2025.44022

Issue

Vol. 64 (2025): Acta Oncologica

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Original article

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Copyright (c) 2025 Faisal Mahmood, Uffe Bernchou, Severin Gråe, Anders Smedegaard Bertelsen, Anne Bisgaard, Rasmus Lübeck Christiansen, Bahar Celik, Elisabeth Kildegaard, Tine Schytte, Rikke Hedegaard Dahlrot

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