Skip to main content

Advertisement

SpringerLink
Log in

Use of FET PET in glioblastoma patients undergoing neurooncological treatment including tumour-treating fields: initial experience

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We present our first clinical experience with O-(2-18F-fluoroethyl)-l-tyrosine (FET) PET in patients with high-grade glioma treated with various neurooncological therapies including tumour-treating fields (TTFields) for the differentiation of tumour progression from treatment-related changes.

Methods

We retrospectively assessed 12 patients (mean age 51 ± 12 years, range 33–72 years) with high-grade glioma (11 glioblastomas, 1 gliosarcoma) in whom the treatment regimen included TTFields and who had undergone FET PET scans for differentiation of tumour progression from treatment-related changes. Mean and maximum tumour-to-brain ratios (TBRmean, TBRmax) were calculated. The definitive diagnosis (tumour progression or posttherapeutic changes) was confirmed either by histopathology (4 of 12 patients) or on clinical follow-up.

Results

In all nine patients with confirmed tumour progression, the corresponding FET PET showed increased uptake (TBRmax 3.5 ± 0.6, TBRmean 2.7 ± 0.7). In one of these nine patients, FET PET was consistent with treatment-related changes, whereas standard MRI showed a newly diagnosed contrast-enhancing lesion. In two patients treated solely with TTFields without any other concurrent neurooncological therapy, serial FET PET revealed a decrease in metabolic activity over a follow-up of 6 months or no FET uptake without any signs of tumour progression or residual tumour on conventional MRI.

Conclusion

FET PET may add valuable information in monitoring therapy in individual patients with high-grade glioma undergoing neurooncological treatment including TTFields.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.

    Article  CAS  PubMed  Google Scholar 

  2. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–22.

    Article  CAS  PubMed  Google Scholar 

  3. Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017;18:1373–85.

    Article  CAS  PubMed  Google Scholar 

  4. Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011;20:1099–106.

    Article  CAS  PubMed  Google Scholar 

  5. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314:2535–43.

    Article  CAS  PubMed  Google Scholar 

  6. Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318:2306–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012;48:2192–202.

    Article  PubMed  Google Scholar 

  8. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology Working Group. J Clin Oncol. 2010;28:1963–72.

    Article  PubMed  Google Scholar 

  9. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990;8:1277–80.

    Article  CAS  PubMed  Google Scholar 

  10. Kumar AJ, Leeds NE, Fuller GN, Van Tassel P, Maor MH, Sawaya RE, et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology. 2000;217:377–84.

    Article  CAS  PubMed  Google Scholar 

  11. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 2008;9:453–61.

    Article  PubMed  Google Scholar 

  12. Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, et al. Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017;19:281–8.

    PubMed  Google Scholar 

  13. Galldiks N, Langen KJ, Pope WB. From the clinician’s point of view – what is the status quo of positron emission tomography in patients with brain tumors? Neuro Oncol. 2015;17:1434–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Langen KJ, Galldiks N, Hattingen E, Shah NJ. Advances in neuro-oncology imaging. Nat Rev Neurol. 2017;13:279–89.

    Article  PubMed  Google Scholar 

  15. Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, et al. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol. 2016;18:1199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Langen KJ, Watts C. Neuro-oncology: amino acid PET for brain tumours – ready for the clinic? Nat Rev Neurol. 2016;12:375–6.

    Article  PubMed  Google Scholar 

  17. Langen KJ, Hamacher K, Weckesser M, Floeth F, Stoffels G, Bauer D, et al. O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2006;33:287–94.

    Article  CAS  PubMed  Google Scholar 

  18. Galldiks N, Dunkl V, Stoffels G, Hutterer M, Rapp M, Sabel M, et al. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[18F]fluoroethyl)-L-tyrosine PET. Eur J Nucl Med Mol Imaging. 2015;42:685–95.

    Article  CAS  PubMed  Google Scholar 

  19. Galldiks N, Stoffels G, Filss C, Rapp M, Blau T, Tscherpel C, et al. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Neuro Oncol. 2015;17:1293–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kebir S, Fimmers R, Galldiks N, Schafer N, Mack F, Schaub C, et al. Late Pseudoprogression in glioblastoma: diagnostic value of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine PET. Clin Cancer Res. 2016;22:2190–6.

    Article  CAS  PubMed  Google Scholar 

  21. Lohmann P, Stoffels G, Ceccon G, Rapp M, Sabel M, Filss CP, et al. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans. Eur Radiol. 2017;27:2916–27.

    Article  PubMed  Google Scholar 

  22. Kebir S, Rauschenbach L, Galldiks N, Schlaak M, Hattingen E, Landsberg J, et al. Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine PET imaging for the detection of checkpoint inhibitor-related pseudoprogression in melanoma brain metastases. Neuro Oncol. 2016;18:1462–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Romagna A, Unterrainer M, Schmid-Tannwald C, Brendel M, Tonn JC, Nachbichler SB, et al. Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET-PET overcome diagnostic uncertainties? Radiat Oncol. 2016;11:139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pöpperl G, Götz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)-L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004;31:1464–70.

    Article  CAS  PubMed  Google Scholar 

  25. Hamacher K, Coenen HH. Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot. 2002;57:853–6.

    Article  CAS  PubMed  Google Scholar 

  26. Langen KJ, Bartenstein P, Boecker H, Brust P, Coenen HH, Drzezga A, et al. German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids. Nuklearmedizin. 2011;50:167–73.

    Article  PubMed  Google Scholar 

  27. Herzog H, Langen KJ, Weirich C, Rota Kops E, Kaffanke J, Tellmann L, et al. High resolution BrainPET combined with simultaneous MRI. Nuklearmedizin. 2011;50:74–82.

    Article  CAS  PubMed  Google Scholar 

  28. Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller HW, et al. O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128:678–87.

    Article  PubMed  Google Scholar 

  29. Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 2010;9:906–20.

    Article  PubMed  Google Scholar 

  30. Ahluwalia MS, Wen PY. Antiangiogenic therapy for patients with glioblastoma: current challenges in imaging and future directions. Expert Rev Anticancer Ther. 2011;11:653–6.

    Article  PubMed  Google Scholar 

  31. Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20.

    Article  CAS  PubMed  Google Scholar 

  32. Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, et al. Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015;16:e534–42.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Preusser M, Lim M, Hafler DA, Reardon DA, Sampson JH. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat Rev Neurol. 2015;11:504–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, et al. MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol. 2008;26:2192–7.

    Article  PubMed  Google Scholar 

  35. Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22:633–8.

    Article  PubMed  Google Scholar 

  36. Galldiks N, Kocher M, Langen KJ. Pseudoprogression after glioma therapy: an update. Expert Rev Neurother. 2017;17:1109–15.

    Article  CAS  PubMed  Google Scholar 

  37. Mohan S, Chawla S, Wang S, Verma G, Skolnik A, Brem S, et al. Assessment of early response to tumor-treating fields in newly diagnosed glioblastoma using physiologic and metabolic MRI: initial experience. CNS Oncol. 2016;5:137–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rachinger W, Goetz C, Pöpperl G, Gildehaus FJ, Kreth FW, Holtmannspotter M, et al. Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery. 2005;57:505–11.

    Article  PubMed  Google Scholar 

  39. Yang I, Aghi MK. New advances that enable identification of glioblastoma recurrence. Nat Rev Clin Oncol. 2009;6:648–57.

    Article  PubMed  Google Scholar 

  40. Galldiks N, Langen K, Holy R, Pinkawa M, Stoffels G, Nolte K, et al. Assessment of treatment response in patients with glioblastoma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MRI. J Nucl Med. 2012;53:1048–57.

    Article  CAS  PubMed  Google Scholar 

  41. Galldiks N, Rapp M, Stoffels G, Fink GR, Shah NJ, Coenen HH, et al. Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]fluoroethyl-L-tyrosine PET in comparison to MRI. Eur J Nucl Med Mol Imaging. 2013;40:22–33.

    Article  CAS  PubMed  Google Scholar 

  42. Mittal S, Barger GR, Bosnyák E, Shah VD, Juhász C. Early metabolic response to tumor-treating fields in patients with recurrent glioblastoma. Cancer Res. 2017;77(13 Suppl):3730.

    Article  Google Scholar 

  43. Bosnyak E, Barger GR, Michelhaugh SK, Robinette NL, Amit-Yousif A, Mittal S, et al. Amino acid PET imaging of the early metabolic response during tumor-treating fields (TTFields) therapy in recurrent glioblastoma. Clin Nucl Med. 2018;43:176–9.

    Article  PubMed  Google Scholar 

Download references

Funding

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

Author information

Author notes

  1. Garry Ceccon, Lazaros Lazaridis, Martin Glas and Norbert Galldiks contributed equally to this work.

Authors and Affiliations

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

    Garry Ceccon, Gereon R. Fink & Norbert Galldiks

  2. Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, Germany

    Lazaros Lazaridis, Sied Kebir & Martin Glas

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

    Gabriele Stoffels, Phillip Lohmann, Gereon R. Fink, Karl-Josef Langen & Norbert Galldiks

  4. Department of Neurosurgery, University of Düsseldorf, Düsseldorf, Germany

    Marion Rapp

  5. Department of Nuclear Medicine, University of Essen, Essen, Germany

    Manuel Weber & Ken Herrmann

  6. Department of Neuropathology, University of Essen, Essen, Germany

    Tobias Blau

  7. Department of Nuclear Medicine, University of Aachen, Aachen, Germany

    Karl-Josef Langen

  8. Center of Integrated Oncology (CIO), University of Cologne, Cologne, Germany

    Norbert Galldiks

Authors
  1. Garry Ceccon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lazaros Lazaridis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriele Stoffels
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marion Rapp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manuel Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tobias Blau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Phillip Lohmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sied Kebir
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ken Herrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gereon R. Fink
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Karl-Josef Langen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Martin Glas
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Norbert Galldiks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norbert Galldiks.

Ethics declarations

Conflicts of interest

None.

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 principles of the1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ceccon, G., Lazaridis, L., Stoffels, G. et al. Use of FET PET in glioblastoma patients undergoing neurooncological treatment including tumour-treating fields: initial experience. Eur J Nucl Med Mol Imaging 45, 1626–1635 (2018). https://doi.org/10.1007/s00259-018-3992-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-018-3992-5

Keywords

Search

Navigation