Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients

ǂa ǂpilot study

Nežka Hribernik (Author), Daniel T. Huff (Author), Andrej Studen (Author), Katarina Zevnik (Author), Žan Klaneček (Author), Hamid Emamekhoo (Author), Katja Škalič (Author), Robert Jeraj (Author), Martina Reberšek (Author)

Abstract

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.

Keywords

melanom;metastatski melanom;imunska nadzorna stikala;molekularni biološki označevalci;melanoma;malignant melanoma;immune-checkpoint inhibitors;molecular imaging biomarkers;

Data

Language:	English
Year of publishing:	2022
Typology:	1.01 - Original Scientific Article
Organization:	OI - Institute of Oncology
Publisher:	Springer Nature
UDC:	616.5
COBISS:	91868163
ISSN:	1619-7070
Views:	11
Downloads:	4
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	melanom;metastatski melanom;imunska nadzorna stikala;molekularni biološki označevalci;
Pages:	str. [1-10]
Volume:	ǂVol. ǂ
Issue:	ǂno. ǂ
Chronology:	2022
DOI:	10.1007/s00259-021-05650-3
ID:	16391584