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Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT

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Abstract

Background

Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy.

Methods

25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients’ best clinical response, assessed at a mean of 59 weeks, was used as reference.

Results

According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients).

Conclusion

Quantitative analysis of 18F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

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Abbreviations

18F-FDG:

2-Deoxy-2-(18F)fluoro-d-glucose

CB:

Clinical benefit

CMR:

Complete metabolic response

CR:

Complete response

CT:

Computed tomography

dPET/CT:

Dynamic positron emission tomography/computed tomography

FD:

Fractal dimension

iCPD:

Confirmed progressive disease

irRC:

Immune-related response criteria

iUPD:

Unconfirmed progressive disease

MB:

Metabolic benefit

MIP:

Maximum intensity projection

No-CB:

No clinical benefit

No-MB:

No metabolic benefit

PD:

Progressive disease

PECRIT PET/CT:

Criteria for early prediction of response to immune checkpoint inhibitor therapy

PERCIMT:

PET response evaluation criteria for immunotherapy

PERCIST:

PET response criteria in solid tumors

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/computed tomography

PMD:

Progressive metabolic disease

PMR:

Partial metabolic response

PR:

Partial response

SD:

Stable disease

SMD:

Stable metabolic disease

SUV:

Standardized uptake value

TAC:

Time activity curve

VOI:

Volume of interest

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Funding

This study was supported in part by the German Cancer Aid under the project with the title “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

Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), 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 of Heidelberg, Heidelberg, Germany

    Julia K. Winkler & Jessica C. Hassel

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

    Annette Kopp-Schneider

  4. Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Lionel Larribere

  5. Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

    Lionel Larribere

  6. Division 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 K. Winkler
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  8. Antonia Dimitrakopoulou-Strauss
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Contributions

CS performed the PET/CT studies, carried out the PET/CT data analysis and drafted the manuscript. HA performed the PET/CT studies. JKW performed the ipilimumab therapies. AKS was responsible for the statistical analysis of the study. LL contributed to draft the manuscript. UH participated in the design of the study. JCH was responsible for the selection of the patients who received the ipilimumab therapy. ADS was responsible for the PET-CT study design and the data evaluation, coordinated the project and contributed to the manuscript.

Corresponding author

Correspondence to Christos Sachpekidis.

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Conflict of interest

Christos Sachpekidis reports travel grants from Janssen-Cilag outside the submitted work. Julia Winkler received speakers honoraria from Merck Sharp & Dohme (MSD), and travel support from AMGEN, Bristol-Myers Squibb (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. The other authors declare that they have no conflict of interest.

Ethical approval

Patients gave written informed consent to participate in the study and to have their medical records released. The study was approved by the Ethical Committee of the University of Heidelberg and the Federal Agency for Radiation Protection (Bundesamt für Strahlenschutz).

Informed consent

Informed consent was obtained from all individual participants included in the study. The patients presented on Figs. 2 and 3 agreed on the publication of these figures. This study does not contain any studies with animals performed by any of the authors.

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Sachpekidis, C., Anwar, H., Winkler, J.K. et al. Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT. Cancer Immunol Immunother 67, 1261–1270 (2018). https://doi.org/10.1007/s00262-018-2183-3

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