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The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma

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Abstract

Purpose

The aim of the present study was to assess the value of interim 18F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy.

Methods

The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients’ best clinical response, assessed at a median of 21.4 months (range 6.3–41.9 months) was used as reference.

Results

According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46).

Conclusion

The application of the recently proposed PERCIMT to interim 18F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.

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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.

Author information

Author notes

  1. Christos Sachpekidis and Hoda Anwar contributed equally to this work.

Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69210, Heidelberg, Germany

    Christos Sachpekidis, Hoda Anwar, 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. Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Lionel Larribere

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

    Uwe Haberkorn

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

Correspondence to Christos Sachpekidis.

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Conflicts of interest

Christos Sachpekidis reports travel grants from Janssen-Cilag outside the submitted work. 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, MSD, Roche, Novartis, Pfizer and is a member of an advisory board for MSD and Amgen. All 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.

Additional information

Jessica C. Hassel and Antonia Dimitrakopoulou-Strauss share joint senior authorship.

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Sachpekidis, C., Anwar, H., Winkler, J. et al. The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma. Eur J Nucl Med Mol Imaging 45, 1289–1296 (2018). https://doi.org/10.1007/s00259-018-3972-9

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  • DOI: https://doi.org/10.1007/s00259-018-3972-9

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