Quantitative Dynamic 18F-FDG PET/CT in Survival Prediction of Metastatic Melanoma under PD-1 Inhibitors.

The advent of novel immune checkpoint inhibitors has led to unprecedented survival rates in advanced melanoma. At the same time, it has raised relevant challenges in the interpretation of treatment response by conventional imaging approaches. In the present prospective study, we explored the predictive role of quantitative, dynamic 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed early during immunotherapy in metastatic melanoma patients receiving treatment with programmed cell death protein 1 (PD-1) inhibitors. Twenty-five patients under PD-1 blockade underwent dynamic and static 18F-FDG PET/CT before the start of treatment (baseline PET/CT) and after the initial two cycles of therapy (interim PET/CT). The impact of semiquantitatively (standardized uptake value, SUV) and quantitatively (based on compartment modeling and fractal analysis) derived PET/CT parameters, both from melanoma lesions and different reference tissues, on progression-free survival (PFS) was analyzed. At a median follow-up of 24.2 months, survival analysis revealed that the interim PET/CT parameters SUVmean, SUVmax and fractal dimension (FD) of the hottest melanoma lesions adversely affected PFS, while the parameters FD of the thyroid, as well as SUVmax and k3 of the bone marrow positively affected PFS. The herein presented findings highlight the potential predictive role of quantitative, dynamic, interim PET/CT in metastatic melanoma under PD-1 blockade. Therefore, dynamic PET/CT could be performed in selected oncological cases in combination with static, whole-body PET/CT in order to enhance the diagnostic certainty offered by conventional imaging and yield additional information regarding specific molecular and pathophysiological mechanisms involved in tumor biology and response to treatment.