20.500.12556/DiRROS-15457 Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients a pilot study Purpose: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear. melanoma malignant melanoma immune-checkpoint inhibitors molecular imaging biomarkers melanom metastatski melanom imunska nadzorna stikala molekularni biološki označevalci true false true Springer Nature Angleški jezik Slovenski jezik by Authors Neznano 2022-09-07 03:37:41 2022-09-07 08:31:54 2022-09-08 03:36:07 0000-00-00 00:00:00 2022 0 0 str. [1-10] no. Vol. 2022 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2021-12-27 616.5 1619-7070 10.1007/s00259-021-05650-3 91868163 RAZ_Hribernik_Nezka_2022.pdf RAZ_Hribernik_Nezka_2022.pdf 1 8A73C7F3392A0EB3317C8F0D91B00005 2ddba3ac4a02871e455d4b18d551a151ad33549e1ba4dc42e34b142223f2ab9f e9f88611-2e65-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20450 Onkološki inštitut Ljubljana 0 0 0