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Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18F-FDG PET/CT, using the patients’ clinical response as reference.

Methods

The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18F-FDG-avid lesions, as well as on the SUV changes after therapy.

Results

The median observation time of the patients after therapy was 21.4 months (range 6.3–41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT).

Conclusion

Our results show that a cut-off of four newly emerged 18F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.

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Funding

This study was supported in part by the German Cancer Aid under the project “Therapy monitoring of ipilimumab based on the quantification of F-18-FDG kinetics with 4D PET/CT (dPET-CT) in patients with melanoma (stage 4)”. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

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Author notes

  1. Hoda Anwar, Christos Sachpekidis, Jessica C. Hassel and Antonia Dimitrakopoulou-Strauss contributed equally to this work.

Authors and Affiliations

  1. Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69210, Heidelberg, Germany

    Hoda Anwar, Christos Sachpekidis, Uwe Haberkorn & Antonia Dimitrakopoulou-Strauss

  2. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany

    Julia Winkler & Jessica C. Hassel

  3. Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany

    Annette Kopp-Schneider

  4. Division of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany

    Uwe Haberkorn

Authors
  1. Hoda Anwar
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  2. Christos Sachpekidis
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  3. Julia Winkler
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  4. Annette Kopp-Schneider
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  5. Uwe Haberkorn
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  6. Jessica C. Hassel
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  7. Antonia Dimitrakopoulou-Strauss
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Corresponding author

Correspondence to Hoda Anwar.

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Conflicts of interest

Julia Winkler received speakers honoraria from MSD, and travel support from AMGEN, BMS, MSD, Philochem and Roche. Jessica C. Hassel received honoraria for talks and travel expenses from BMS. The other authors declare no conflicts of interest.

Ethical approval

The study was approved by the Ethics Committee of the University of Heidelberg (S-107/2012) and the Federal Agency for Radiation Protection (Bundesamt für Strahlenschutz).

Informed consent

Informed consent was obtained from all individual participants included in the study. This study did not include any studies with animals performed by any of the authors.

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Anwar, H., Sachpekidis, C., Winkler, J. et al. Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab. Eur J Nucl Med Mol Imaging 45, 376–383 (2018). https://doi.org/10.1007/s00259-017-3870-6

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  • DOI: https://doi.org/10.1007/s00259-017-3870-6

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