18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

  • Ferdinand Seith
  • Andrea Forschner
  • Holger Schmidt
  • Christina Pfannenberg
  • Brigitte Gückel
  • Konstantin Nikolaou
  • Christian la Fougère
  • Claus Garbe
  • Nina Schwenzer
Short Communication

Abstract

Purpose

The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation.

Methods

Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t0, base-line), two weeks (t1, study examination) and three months after treatment initiation (t2, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients.

Results

Three patients with partial metabolic response in PET at t1 turned out to have complete response at t2. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t2, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t1. OS in patients with PMD at t2 varied between 148 and 814 days. SMD at both t1 and t2 was seen in one patient, tumor progress was observed after 308 days.

Conclusion

Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future.

Keywords

18F-FDG-PET Melanoma Immunotherapy Early response assessment 

Notes

Acknowledgements

We wish to cordially thank all patients who agreed to participate in this study.

We thank Carsten Groeper, Gerd Zeger and Henriette Heners for the acquisition of images and the friendly care of patients.

Compliance with ethical standards

Conflict of interest

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. This study was approved by the local ethics committee of the University of Tuebingen (code: 251/2012BO1).

Informed consent

Informed consent was obtained from all patients included in this study.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. https://doi.org/10.3322/caac.21332.CrossRefPubMedGoogle Scholar
  2. 2.
    American Cancer Society. Cancer Fact and Figures 2016. Am Cancer Soc 2016. http://hypno-chemo-cancer-hypnosis-us.com/pdf's/2016cancerfacts.pdf. Accessed December 12, 2016.Google Scholar
  3. 3.
    U.S. Food and Drug Administration. Hematology/Oncology (Cancer) Approvals & Safety Notifications.Google Scholar
  4. 4.
    Bagcchi S. Pembrolizumab for treatment of refractory melanoma. The Lancet Oncology. 2014;15(10):e419.CrossRefPubMedGoogle Scholar
  5. 5.
    Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. https://doi.org/10.1056/NEJMoa1412082.CrossRefPubMedGoogle Scholar
  6. 6.
    Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517–9. https://doi.org/10.1056/NEJMe1205943.CrossRefPubMedGoogle Scholar
  7. 7.
    Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18. https://doi.org/10.1016/s1470-2045(15)00083-2.CrossRefPubMedGoogle Scholar
  8. 8.
    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32. https://doi.org/10.1056/NEJMoa1503093.CrossRefPubMedGoogle Scholar
  9. 9.
    Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–44. https://doi.org/10.1056/NEJMoa1305133.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Europe J Can (Oxford, England : 1990). 2009;45(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026.Google Scholar
  11. 11.
    Pfannenberg C, Aschoff P, Schanz S, Eschmann SM, Plathow C, Eigentler TK, et al. Prospective comparison of 18F–fluorodeoxyglucose positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced malignant melanoma. Europe J Can (Oxford, England : 1990). 2007;43(3):557–64. https://doi.org/10.1016/j.ejca.2006.11.014.Google Scholar
  12. 12.
    Reinhardt MJ, Joe AY, Jaeger U, Huber A, Matthies A, Bucerius J, et al. Diagnostic performance of whole body dual modality 18F-FDG PET/CT imaging for N- and M-staging of malignant melanoma: experience with 250 consecutive patients. J Clin Oncol : Off J Am Soc Clin Oncol. 2006;24(7):1178–87. https://doi.org/10.1200/jco.2005.03.5634.CrossRefGoogle Scholar
  13. 13.
    McArthur GA, Puzanov I, Amaravadi R, Ribas A, Chapman P, Kim KB, et al. Marked, homogeneous, and early [18F]fluorodeoxyglucose-positron emission tomography responses to vemurafenib in BRAF-mutant advanced melanoma. J Clin Oncol : Off J Am Soc Clin Oncol. 2012;30(14):1628–34. https://doi.org/10.1200/jco.2011.39.1938.CrossRefGoogle Scholar
  14. 14.
    Sachpekidis C, Larribere L, Pan L, Haberkorn U, Dimitrakopoulou-Strauss A, Hassel JC. Predictive value of early 18F-FDG PET/CT studies for treatment response evaluation to ipilimumab in metastatic melanoma: preliminary results of an ongoing study. Eur J Nucl Med Mol Imaging. 2015;42(3):386–96. https://doi.org/10.1007/s00259-014-2944-y.CrossRefPubMedGoogle Scholar
  15. 15.
    Cho SY, Lipson EJ, Im HJ, Rowe SP, Mena E, Blackford A, et al. Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early Time-Point FDG-PET/CT Imaging in Patients with Advanced Melanoma. J Nucl Med : Off Publ, Soc Nucl Med. 2017; https://doi.org/10.2967/jnumed.116.188839.
  16. 16.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med : Off Publ, Soc Nucl Med. 2009;50(Suppl 1):122S–50S. https://doi.org/10.2967/jnumed.108.057307.CrossRefGoogle Scholar
  17. 17.
    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 Can Res : Off J Am Assoc Cancer Res. 2009;15(23):7412–20. https://doi.org/10.1158/1078-0432.ccr-09-1624.CrossRefGoogle Scholar
  18. 18.
    Wong AN, McArthur GA, Hofman MS, Hicks RJ. The advantages and challenges of using FDG PET/CT for response assessment in melanoma in the era of targeted agents and immunotherapy. Eur J Nucl Med Mol Imaging. 2017; https://doi.org/10.1007/s00259-017-3691-7.
  19. 19.
    Lipson EJ, Velculescu VE, Pritchard TS, Sausen M, Pardoll DM, Topalian SL, et al. Circulating tumor DNA analysis as a real-time method for monitoring tumor burden in melanoma patients undergoing treatment with immune checkpoint blockade. J Immunotherapy Cancer. 2014;2(1):42. https://doi.org/10.1186/s40425-014-0042-0.CrossRefGoogle Scholar
  20. 20.
    Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98–106. https://doi.org/10.1097/coc.0000000000000239.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9. https://doi.org/10.1038/nature10673.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. https://doi.org/10.1056/NEJMoa1504030.CrossRefPubMedGoogle Scholar
  23. 23.
    Petralia G, Padhani A, Summers P, Alessi S, Raimondi S, Testori A, et al. Whole-body diffusion-weighted imaging: is it all we need for detecting metastases in melanoma patients? Eur Radiol. 2013;23(12):3466–76. https://doi.org/10.1007/s00330-013-2968-x.CrossRefPubMedGoogle Scholar
  24. 24.
    Simoncic U, Leibfarth S, Welz S, Schwenzer N, Schmidt H, Reischl G, et al. Comparison of DCE-MRI kinetic parameters and FMISO-PET uptake parameters in head and neck cancer patients. Med Phys. 2017;44(6):2358–68. https://doi.org/10.1002/mp.12228.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Ferdinand Seith
    • 1
  • Andrea Forschner
    • 2
  • Holger Schmidt
    • 1
  • Christina Pfannenberg
    • 1
  • Brigitte Gückel
    • 1
  • Konstantin Nikolaou
    • 1
    • 3
  • Christian la Fougère
    • 3
    • 4
  • Claus Garbe
    • 2
  • Nina Schwenzer
    • 1
  1. 1.Diagnostic and Interventional Radiology, Department of RadiologyEberhard Karls UniversityTuebingenGermany
  2. 2.Department of DermatologyEberhard Karls UniversityTuebingenGermany
  3. 3.German Cancer Consortium (DKTK)HeidelbergGermany
  4. 4.Nuclear Medicine and Clinical Molecular Imaging, Department of RadiologyEberhard Karls UniversityTuebingenGermany

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