Abstract
Simple SummaryImmune checkpoint inhibitor (ICI) therapy has changed the management of many cancers endowed with poor prognosis. However, cardiotoxicity, as well as the possible progression of atherosclerosis, have been described. 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated tool to quantify atherosclerotic inflammatory activity; therefore, we found it interesting to analyze the changes in maximum FDG standardized uptake values (SUVmax) and of target-to-background ratios (TBRs) in 117 arterial segments of 12 otherwise healthy, young lymphoma patients, underwent PET pre/post ICI treatment. As systemic immune activation surrogate markers, SUVmax of the bone marrow, spleen, and liver, as well high-sensitivity C-reactive protein (hsCRP) pre- and post-treatment, were additionally analyzed. ICI therapy induced arterial inflammatory activity, detected by increased TBR in all PET lesions. FDG uptake measured in other organs and hsCRP levels remained unchanged. Our findings show that cancer immunotherapy with ICI might be a critical moderator of atherosclerosis, with a possible subsequently increased risk of future cardiovascular events in oncological patients, even in young patients with low cardiovascular risk.Background: Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. Methods: We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUVmax) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. Results: ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, p < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, p < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. Conclusions: Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.
Highlights
Targeted therapies are amongst the major treatment options for cancer today
Twelve lymphoma patients treated with PD-1 inhibitors who underwent FDG positron emission tomography–computer tomography (PET/CT) or positron emission tomography–magnetic resonance imaging (PET/MRI) scans performed for diagnostic purposes before and after treatment were retrospectively analyzed
Immune checkpoint inhibitors (ICI) immunotherapy resulted in significant increases in the inflammatory activity in all assessed arterial PET lesions (n = 117, lesional TBRpre = 1.50 ± 0.42 vs. lesional TBRpost = 1.79 ± 0.46, p < 0.001) (Figure 1A)
Summary
Targeted therapies are amongst the major treatment options for cancer today. Immune checkpoint inhibitors (ICI) targeting programmed death-1/ligand-1 (PD-1/PD-L1) have transformed the management of different prognostically poor cancers [1,2,3]. Positron emission tomography (PET) with 2-[18F]fluorodeoxyglucose (FDG) is a validated tool to assess atherosclerotic inflammatory activity, including in cancer patients [7,8]. Methods: We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Results: ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs TBRneg_post = 1.71 ± 0.45, p < 0.001), whereas already-inflamed lesions remained unchanged. Conclusions: the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients
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