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Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine

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Abstract

Background

The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression.

Methods

After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33–75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8–10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates.

Results

Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006).

Conclusions

FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

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Funding

This work was supported by the Wilhelm-Sander Stiftung, Germany (grant number 2016.069.1).

Author information

Author notes

  1. Norbert Galldiks and Veronika Dunkl contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, University Hospital Cologne, Josef-Stelzmann St. 9, 50937, Cologne, Germany

    Norbert Galldiks, Veronika Dunkl, Garry Ceccon, Caroline Tscherpel, Jan Steger, Elena K. Bauer & Gereon R. Fink

  2. Institute of Neuroscience and Medicine (INM-3, -4), Forschungszentrum Juelich, Leo-Brandt-St. 5, 52425, Juelich, Germany

    Norbert Galldiks, Caroline Tscherpel, Gabriele Stoffels, Philipp Lohmann, Nadim J. Shah, Gereon R. Fink & Karl-Josef Langen

  3. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Cologne, Germany

    Norbert Galldiks

  4. Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Ian Law & Otto M. Henriksen

  5. Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Aida Muhic & Hans S. Poulsen

  6. Dept. of Nuclear Medicine, University Hospital Cologne, Cologne, Germany

    Matthias Schmidt

  7. Department of Neurology, University Hospital Aachen, Aachen, Germany

    Nadim J. Shah

  8. Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany

    Karl-Josef Langen

Authors
  1. Norbert Galldiks
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  2. Veronika Dunkl
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Corresponding author

Correspondence to Norbert Galldiks.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed written consent was obtained from all individual participants included in the study.

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Galldiks, N., Dunkl, V., Ceccon, G. et al. Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine. Eur J Nucl Med Mol Imaging 45, 2377–2386 (2018). https://doi.org/10.1007/s00259-018-4082-4

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  • DOI: https://doi.org/10.1007/s00259-018-4082-4

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