Arterial inflammation induced by immune checkpoint inhibitors assessed on 18F-FDG PET-CT scans in stage III/IV melanoma patients

Abstract

Abstract Background In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, as they lead to a substantial improvement in the prognosis of cancer patients. In high-grade melanoma patients, ICIs have doubled the three-year survival rate. However, ICIs may not only increase the immune response to tumor cells, but also to non-tumor cells, potentially inducing pro-atherogenic effects that can result in increased vascular inflammation and subsequent cardiovascular events. Purpose The objective of this study is to assess differences in vascular inflammation in the large arteries, as detected by 18F-FDG PET-CT scans, between stage III/IV melanoma patients receiving ICI therapy compared to stage III/IV melanoma patients not treated with ICIs. Methods The study population consisted of a cohort stage III/IV melanoma patients who underwent PET-CT scans at baseline, defined as < 1 year after diagnosis of stage III/IV melanoma and at T1 and T2, 6 months and 18 months after the baseline scan respectively. Patients with a history of cardiovascular events, treated with statins or corticosteroids (prednisolone > 10 mg per day) were excluded. Vascular inflammation was evaluated in the following eight arterial segments: the left and right carotid artery, ascending aorta, aortic arch, thoracic descending aorta, abdominal aorta and the left and right iliac artery. For each segment, the maximum standardized uptake value (SUV) for 18F-FDG uptake was derived and target-to-background ratio (TBR) was calculated from the ratio of the maximum SUV of the segment and the mean SUV of the superior and inferior vena cava. Vascular inflammation was defined as the total TBR per patient, calculated by sum of the TBR values of the eight arterial segments. The study endpoint was the difference in the increase in total TBR between patients treated with ICIs (exposure group) and patients without ICI treatment (control group). Results A total of 70 stage III/IV melanoma patients of whom 46 received ICIs and 24 did not receive ICI therapy were analyzed in this study. The median age at diagnosis was 61 years [IQR: 49-69] and 37 patients (52.9%) were female. The exposure group had a median ICI treatment of 9 [6-13] cycles. The results showed a significant difference in the TBR between the baseline PET-CT scan and T1 between the two groups. The control group showed a decrease in TBR by -0.33 [95% CI: -0.66 – 0.01], whereas the exposure group showed an increase in TBR by 0.17 [-0.14 – 0.49] (p = 0.045). No differences in TBR were found between T1 and T2. Conclusion The present study demonstrated that in stage III/IV melanoma patients treated with ICIs, there was a significant increase in vascular inflammation assessed by PET-CT in the large arteries during the first six months after treatment initiation, as compared to a control group without ICI treatment.∆TBR on PET-CT between baseline and T1∆TBR on PET-CT between T1 and T2