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Cancer Immunology, Immunotherapy

, Volume 68, Issue 5, pp 813–822 | Cite as

Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

  • Antonia Dimitrakopoulou-StraussEmail author
Focussed Research Review

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on 18F-FDG PET–CT. The classical criteria used for therapy monitoring with 18F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with 18F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the 18F-FDG images for response assessment. Finally, the definition of 18F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.

Keywords

PET Melanoma Immunotherapy monitoring PIVAC 17 

Abbreviations

CB

Clinical benefit

CR

Complete remission

CT

Computed tomography

CTLA-4

Cytotoxic T lymphocyte-associated Ag 4

EORTC

European Organisation for Research and Treatment of Cancer

FD

Fractal dimension

FDA

Food and Drug Administration

18F-FDG

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

18F-FLT

18F-3′-Fluoro-3′-deoxythymidine

Ga-68

Gallium-68

GIST

Gastrointestinal stromal tumor

ICI

Immune checkpoint inhibitors

iCPD

Immune-related confirmed progressive disease

irAE

Immune-related adverse events

iRECIST

Immune-related Response Evaluation Criteria in Solid Tumors

irRC

Immune-related response criteria

iUPD

Immune-related unconfirmed progressive disease

LDH

Lactate dehydrogenase

Lu-177

Lutetium-177

MAPK

Mitogen-activated protein kinase

MDSC

Myeloid-derived suppressor cells

MIP

Maximum intensity projection

MRI

Magnetic resonance imaging

mWHO

Modified World Health Organisation

NK cells

Natural killer cells

No-CB

No clinical benefit

OS

Overall survival

PD

Progressive disease

PD-1

Programmed death 1 receptor

PERCIMT

PET Response Evaluation Criteria for Immunotherapy

PERCIST

PET Response Criteria in Solid Tumors

PET

Positron emission tomography

PFS

Progression-free survival

PMD

Progressive metabolic disease

PMR

Partial metabolic response

PR

Partial remission

RECIST

Response Evaluation Criteria in Solid Tumors

ROI

Region of interest

SD

Stable disease

SMD

Stable metabolic disease

SSTR

Somatostatin receptor

SUL

Standardized uptake value normalized for lean body mass

SUV

Standardized uptake value

TCR

T-cell receptor for Ag

TIL

Tumor-infiltrating lymphocyte

VEGF

Vascular endothelial growth factor

WHO

World Health Organisation

Y-90

Yttrium-90

Notes

Acknowledgements

The author would like to thank Jessica Hassel, MD, for her contribution to all PET–CT studies in melanoma patients.

Funding

Some of the studies mentioned in this review are based on funding upon the German Cancer Aid under the project with the title “Therapy monitoring of ipilimumab based on the quantification of 18F-FDG kinetics with 4D PET/CT (dPET–CT) in patients with melanoma (stage 4)”. The funders had no role in the preparation of this review. No additional external funding was received for this review.

Compliance with ethical standards

Conflict of interest

The author declares that she has no conflict of interest.

Ethical approval

Not applicable. This is a review and not an original paper.

Informed consent

Not applicable. This is a review and not an original paper. All patients agreed on the publication of their images.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Cooperation Unit Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany

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