1Universitäts-Herzzentrum Freiburg - Bad Krozingen Klinik für Kardiologie und Angiologie Freiburg im Breisgau, Deutschland; 2Institut für Medizinische Biometrie und Statistik Freiburg, Deutschland; 3Universitätsklinikum Freiburg Klinik für Nuklearmedizin Freiburg im Breisgau, Deutschland
Background
Immunotherapy has transformed cancer therapy. However, whether Immune Checkpoint Inhibitor (ICI) therapy promotes atherosclerosis through the exacerbation of low-grade vascular inflammation is under debate. Repeated 18F-FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose) positron emission tomography–computed tomography (PET-CT) allows for longitudinal monitoring of low-grade inflammation.
Methods
159 consecutive cancer patients ≥ 65 years of age, who underwent an initial PET-CT (PET-CT0) followed by three subsequent PET-CTs between January 2010 and May 2023, were included in this retrospective analysis. To generate an atlas of vascular low-grade inflammation, 18F-FDG uptake in the vascular wall was quantified and followed up longitudinally by assessing target to background ratios (TBR) in a standardized manner. A total of 3,790 TBRs were determined at six pre-specified anatomic landmarks: left (LCB) and right (RCB) carotid bifurcation, the aorta at the level of the brachiocephalic trunk (BT), the aorta at the left renal artery (RA), aortic bifurcation (AB), and femoral artery (FA). Time-dependent multivariable regression analyses to assess the longitudinal trajectories of the TBR ratios were calculated. All models were adjusted for the TBR at PET-CT0, and for calcifications close to a landmark (± 1cm), and considered fixed and random effects.
Results
Median age was 73 years (IQR 68, 76.5) and n = 51 (32 %) patients received ICI treatment directly after PET-CT0. At each anatomic landmark, the TBR at PET-CT0 did not differ between patients with and without ICI treatment. Over a median follow-up of 725 days (IQR 658, 770), the TBR increased by + 1.5 % per year (95% confidence interval (CI) +1.1 %, + 2.0 %, p < 0.001) when considering all landmarks across all patients. Statin use was associated with lesser TBR increases (p = 0.069), whereas calcifications close to a landmark were associated with higher TBR increases (p = 0.047). However, ICI therapy was not associated with TBR trajectories, neither in the basic regression model (p = 0.693), nor in a regression model additionally adjusted for statin use and BMI (p = 0.631). No significant associations between ICI therapy and TBR trajectories were also observed in a sensitivity analysis restricted to patients with melanoma (n = 81), of whom n = 49 (60.5 %) received ICI treatment (p = 0.54). Although TBR increases differed at regional level, with the lowest trajectories at FA (+ 0.9 per year [CI - 0. %, + 2.1 %]) and the highest trajectories at LCB (+ 2.2 % per year [CI + 1%, + 3.3%]), ICI therapy did not affect TBR trajectories at any anatomic landmark. Further analyses will clarify whether double ICI therapy, side effects of ICI therapy, or corticosteroid-use within the ICI treated group may have influenced TBR trajectories.
Conclusion
In this systematic analysis of cancer patients at considerable cardiovascular risk, ICI therapy had no association with the long-term trajectories of vascular low-grade inflammation assessed by 18F-FDG uptake in follow-up PET-CTs. Future studies need to assess whether progression of low-grade inflammation as assessed by PET-CTs in patients under ICI therapy may identify a subgroup of patients at higher risk for cardiovascular events.