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Abstract: A considerable proportion of metastatic melanoma (mM) patients do not respond to immune checkpoint inhibitors (ICIs). There is a great need to develop noninvasive biomarkers to detect patients, who do not respond to ICIs early during the course of treatment. The aim of this study was to evaluate the role of early [18F]2fluoro- 2-deoxy-D-glucose PET/CT (18F-FDG PET/CT) at week four (W4) and other possible prognostic biomarkers of survival in mM patients receiving ICIs. Patients and methods. In this prospective noninterventional clinical study, mM patients receiving ICIs regularly underwent 18F-FDG PET/CT: at baseline, at W4 after ICI initiation, at week sixteen and every 16 weeks thereafter. The tumor response to ICIs at W4 was assessed via modified European Organisation for Research and Treatment of Cancer (EORTC) criteria. Patients with progressive metabolic disease (PMD) were classified into the no clinical benefit group (no-CB), and those with other response types were classified into the clinical benefit group (CB). The primary end point was survival analysis on the basis of the W4 18F-FDG PET/CT response. The secondary endpoints were survival analysis on the basis of LDH, the number of metastatic localizations, and immune-related adverse events (irAEs). Kaplan-Meier analysis and univariate Cox regression analysis were used to assess the impact on survival. Results. Overall, 71 patients were included. The median follow-up was 37.1 months (95% CI = 30.1–38.0). Three (4%) patients had only baseline scans due to rapid disease progression and death prior to W4 18F-FDG-PET/CT. Fifty-one (72%) patients were classified into the CB group, and 17 (24%) were classified into the no-CB group. There was a statistically significant difference in median overall survival (OS) between the CB group (median OS not reached [NR]; 95% CI = 17.8 months – NR) and the no-CB group (median OS 6.2 months; 95% CI = 4.6 months – NR; p = 0.003). Univariate Cox analysis showed HR of 0.4 (95% CI = 0.18 – 0.72; p = 0.004). median OS was also significantly longer in the group with normal serum LDH levels and the group with irAEs and cutaneous irAEs. Conclusions. Evaluation of mM patients with early 18F-FDG-PET/CT at W4, who were treated with ICIs, could serve as prognostic imaging biomarkers. Other recognized prognostic biomarkers were the serum LDH level and occurrence of cutaneous irAEs.
Keywords: melanoma, prognostic biomarkers, survival, immunotherapy
Published in DiRROS: 21.11.2025; Views: 442; Downloads: 169
Full text (1,26 MB)

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: melanoma, malignant melanoma, immune-checkpoint inhibitors, molecular imaging biomarkers
Published in DiRROS: 07.09.2022; Views: 1915; Downloads: 660
Full text (9,65 MB)