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

• Published in: European journal of nuclear medicine and molecular imaging 2022-05, Vol.49 (6), p.1857-1869
• Main Authors: Hribernik, Nežka, Huff, Daniel T, Studen, Andrej, Zevnik, Katarina, Klaneček, Žan, Emamekhoo, Hamid, Škalic, Katja, Jeraj, Robert, Reberšek, Martina
• Format: Article
• Language: English
• Subjects: Advanced Image Analyses (Radiomics and Artificial Intelligence); Adverse events; Artificial neural networks; Biomarkers; Cardiology; Computed tomography; Confidence intervals; CTLA-4 protein; Fluorine isotopes; Fluorodeoxyglucose F18; Humans; Imaging; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Intestine; Lungs; Medical imaging; Medicine; Medicine & Public Health; Melanoma; Melanoma - diagnostic imaging; Melanoma - drug therapy; Melanoma, Cutaneous Malignant; Metastases; Neoplasms, Second Primary; Neural networks; Nuclear Medicine; Oncology; Organs; Original; Original Article; Orthopedics; Patients; PD-1 protein; Pilot Projects; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography - methods; Radiology; Retrospective Studies; Skin cancer; Skin Neoplasms; Thyroid; Thyroid gland; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-021-05650-3

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.