Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study.

Autor: Hribernik N; Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloška 2, SI-1000, Ljubljana, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Huff DT; Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; University of Wisconsin Carbone Cancer Centre, Madison, WI, USA., Studen A; Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia.; Jožef Stefan Institute, Ljubljana, Slovenia., Zevnik K; Department of Nuclear Medicine, Institute of Oncology Ljubljana, Ljubljana, Slovenia., Klaneček Ž; Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia., Emamekhoo H; University of Wisconsin Carbone Cancer Centre, Madison, WI, USA.; Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., Škalic K; Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., Jeraj R; Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; University of Wisconsin Carbone Cancer Centre, Madison, WI, USA.; Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia.; Jožef Stefan Institute, Ljubljana, Slovenia., Reberšek M; Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloška 2, SI-1000, Ljubljana, Slovenia. mrebersek@onko-i.si.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. mrebersek@onko-i.si.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2022 May; Vol. 49 (6), pp. 1857-1869. Date of Electronic Publication: 2021 Dec 27.
DOI: 10.1007/s00259-021-05650-3
Abstrakt: 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 18 F-FDG PET/CT.
Methods: 18 F-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 (SUV X% ) of 18 F-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 18 F-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 (SUV 95% , AUROC=0.79), lung (SUV 95% , AUROC=0.98), and thyroid (SUV 75% , AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV 95% >2.7 g/mL), lung (SUV 95% >1.7 g/mL), and thyroid (SUV 75% >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 18 F-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 18 F-FDG PET/CT well before clinical symptoms appear.
(© 2021. The Author(s).)
Databáze: MEDLINE
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