Arterial inflammation on [18F]FDG PET/CT in melanoma patients treated with and without immune checkpoint inhibitors: CHECK-FLAME I

Background and aims Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified. This study aims to assess differences in increase in arterial inflammation between patients with advanced melanoma treated with ICIs compared to a control group without ICIs. Methods Patients with advanced melanoma who underwent [ 18 F]FDG PET/CT scans at baseline, 6 months (T1) and 18 months (T2) were included in this retrospective observational study. Arterial inflammation was evaluated in eight segments by calculating the target-to-background ratio (TBR). The primary study outcome was the difference in increase in mean TBR max between patients treated with and without ICIs. Results We included 132 patients of whom 72.7 % were treated with ICIs. After exclusion for the use of anti-inflammatory medication, patients treated with ICIs showed a significant increase in mean TBR max between baseline and T1 from 1.29 ± 0.12 to 1.33 ± 0.13 ( p = 0.017), while in the control group, no change in mean TBR max (1.30 ± 0.12 to 1.28 ± 0.10, p = 0.22) was observed ( p = 0.027). During longer follow-up, mean TBR max remained stable in both groups. Arterial inflammation increased significantly after ICI therapy in patients without active inflammation ( p < 0.001) and in patients without calcifications ( p = 0.013). Conclusions A significant increase in arterial inflammation as measured on [ 18 F]FDG PET/CT was observed in patients with advanced melanoma treated with ICIs only in the first six months after initiation of therapy, whereas no changes were observed in the control group. Moreover, arterial inflammation was mainly increased in patients without pre-existing inflammatory activity and with non-calcified lesions.