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

SIMPLE SUMMARY: The reliable and early during-the-course-of-treatment assessment of tumor response to the novel immunotherapeutic agents is a matter of debate, posing relevant challenges to conventional imaging modalities. In this prospective study, including 25 metastatic melanoma patients, we explored the prognostic significance of quantitative, dynamic (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) performed early during programmed cell death protein 1 (PD-1) blockade. At a median follow-up of 24.2 months, several semiquantitative and quantitative PET/CT parameters derived from tumor lesions and reference tissues had an impact on progression-free survival (PFS). In particular, (18)F-FDG standardized uptake value (SUV(mean), SUV(max)) and fractal dimension (FD) of melanoma lesions adversely affected PFS, while FD of the thyroid, as well as SUV(max) and k(3) of the bone marrow, positively affected PFS. These findings underline the potential predictive role of quantitative, dynamic, interim PET/CT—performed in combination with conventional, static, whole-body PET/CT—in metastatic melanoma patients under PD-1 blockade. ABSTRACT: 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 (18)F-fluorodeoxyglucose ((18)F-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 (18)F-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 SUV(mean), SUV(max) and fractal dimension (FD) of the hottest melanoma lesions adversely affected PFS, while the parameters FD of the thyroid, as well as SUV(max) and k(3) 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.