Longitudinal Assessment of Subclinical Arterial Inflammation in Patients Receiving Immune Checkpoint Inhibitors by Sequential [F]FDG PET Scans.

Background: Immune checkpoint inhibitors (ICIs), though revolutionary in cancer treatment, may accelerate atherosclerosis by inducing arterial inflammation. Due to a lack of controlled studies, the capacity of arterial 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) uptake in patients with cancer to detect this arterial inflammation remains unclear.

Methods: Arterial [F]FDG uptake at 6 anatomic landmarks was assessed on serial positron emission tomography scans in patients with cancer treated at a German University Hospital between January 2010 and May 2023. Patients aged ≥65 years with at least 4 sequential scans within 30 months were included. Linear mixed regression analyses were used to evaluate the change in arterial tracer uptake in patients who received ICI or not.

Results: Of the 156 patients included, 50 (30.1%) received ICIs after the baseline scan. Baseline arterial [F]FDG uptake correlated with traditional cardiovascular risk factors, such as body mass index and male sex. Cross-sectional analyses suggested a negative effect of cholesterol-lowering medication on arterial [F]FDG uptake at follow-up. In a time-dependent interaction analysis, arterial [F]FDG uptake increased by 0.8% annually in patients without ICIs (95% CI, 0.2%-1.4%), potentially reflecting the background progression of arterial inflammation in patients with cancer. In ICI users, [F]FDG uptake increased by 2.5% annually (95% CI, 1.7%-3.3%; =0.001 for interaction with no ICI). Higher annual increase rates in ICI users were consistent across several anatomic landmarks, preexisting cardiovascular disease status, arterial calcification status, and concomitant chemotherapy or steroid use. However, this effect did not reach statistical significance in patients with melanoma and those with prior irradiation therapy.

Conclusions: This is the first controlled clinical study supporting the role of ICIs in accelerating atherosclerosis through low-grade arterial inflammation. However, although detectable by repeated [F]FDG scans, the increase in tracer uptake associated with ICI use was modest compared with individual variability, questioning whether [F]FDG captures the full pathophysiological process of ICI-induced, lymphocyte-driven inflammation.