December 2021 - Raffaella Calabretta

Dr. Raffaella Calabretta

MedUni Wien RESEARCHER OF THE MONTH December 2021

Besides typical cardiovascular risk factors, cardio-toxicity induced by antineoplastic drugs remains a critical issue. Cancer immunotherapy with immune checkpoint inhibitors (ICI), such as monoclonal antibodies targeting PD-1 (Nivolumab, Pembrolizumab), PD-L1 (Atezolizumab), or CTLA-4 (Ipilimumab), stimulate previously inactivated cytotoxic T-cells to recognize and target cancer cells. Interference with the CTLA-4 and PD-1 axes can cause immune-related adverse events, which in some cases leads to serious and potentially fatal cardiovascular toxicity. Previous studies suggested that PET/CT with 18[F] - Fluorodeoxyglucose (FDG) is a valid tool to quantify atherosclerotic inflammatory activity and predicted severe cardio- and cerebrovascular events in oncological patients.
20 patients with melanoma treated with ICI and available FDG PET/CT scans before and during/after treatment have been retrospectively analyzed. FDG maximum standardized uptake values (SUV_max) and SUV_bloodpool for bloodpool correction of FDG were derived and target-to-background ratios (TBRs) were calculated. As surrogate markers of systemic immune cell activation, FDG uptake was also measured in bone marrow and in spleen before and after ICI therapy. Cancer immunotherapy with ICI resulted in a significant increase of arterial inflammatory activity. FDG uptake measured before and after ICI therapy in bone marrow and in spleen did not show statistical differences.
Significantly increasing FDG-uptake in the large arteries is pointing towards an induction of inflammatory activity after cancer immunotherapy with ICI and might cause increased cardio-/cerebrovascular complications.

Raffaella Calabretta, MD¹, Christoph Hoeller², MD, Verena Pichler, PhD¹, Markus Mitterhauser, PhD¹, Georgios Karanikas, MD¹, Alexander Haug, MD¹, Xiang Li, PhD¹*, Marcus Hacker, MD¹*

*shared last authorship

¹ Division of Nuclear Medicine, Dept. of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria. ² Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Selected Literature

1. Calabretta R, Hoeller C, Pichler V, Mitterhauser M, Karanikas G, Haug A, Li X, Hacker M. Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in Large Arteries. Circulation. 2020 Sep 8. doi:10.1161/CIRCULATIONAHA.120.048708
2. Escudier M, Cautela J, Malissen N, Ancedy Y, Orabona M, Pinto J, Monestier S, Grob JJ, Scemama U, Jacquier A, Lalevee N, Barraud J, Peyrol M, Laine M, Bonello L, Paganelli F, Cohen A, Barlesi F, Ederhy S, Thuny F. Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity. Circulation. 2017 Nov 21;136(21):2085-2087.
3. Lutgens E, Seijkens TTP. Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease. J Immunother Cancer. 2020 Feb;8(1).
4. Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, Nikolaou K, Reiser MF, Bartenstein P, Hacker M. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med. 2009 Oct;50(10):1611-20.
5. Li X, Heber D, Rausch I, Beitzke D, Mayerhoefer ME, Rasul S, Kreissl M, Mitterhauser M, Wadsak W, Hartenbach M, Haug A, Zhang X, Loewe C, Beyer T, Hacker M. Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system. Eur J Nucl Med Med Mol Imaging. 2016 Jul;43(8):1503-12.