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

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-(F-18)fluoro-d-glucose (F-18-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 F-18-FDG PET-CT. The classical criteria used for therapy monitoring with F-18-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 F-18-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the F-18-FDG images for response assessment. Finally, the definition of F-18-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.