18F-FDG PET/CT for the detection of immune-related adverse events in patients with metastatic melanoma receiving immunotherapy

Introduction: To determine the frequency and type of immune-related adverse events (IRAE) detected on ¹⁸F-FDG PET/CT in patients with metastatic melanoma receiving immunotherapy, and to assess its impact on patient management.

Methods: We conducted a retrospective cohort study, including patients with metastatic melanoma receiving immunotherapy, referred for ¹⁸F-FDG PET/CT (= PET CT) during the last 12 years. PET CT images and imaging reports were reviewed to identify findings suggestive of IRAE. Reference standard to determine the presence or IRAE consisted of clinical assessment, physical examination, confirmatory laboratory tests, correlative imaging, endoscopy and/or biopsy. Demographic data at staging, immunotherapy regimen, type of IRAE and severity were documented. At the timepoint level we determine the diagnostic performance of PET/CT, and at the event level we determine the detection rate.

Results: We evaluated 147 patients at 201 timepoints during the course of their disease. The majority, 87/147 (59.2%) were men, with an average age of 61.4 ±14.7 years (range 26- 88). A total of 35 patients had more than 1 scan, with a median time between scans of 4.78 months (1.01 – 17.2). PET CT performed as follows for the detection of IRAE: sensitivity of 81.8%, specificity of 98.1%, PPV of 92.3% and NPV of 95.1%. The calculated detection rate was of 84.3% (43/51). Among true positive findings, 14/43 (32.6%) were not suspected clinically but confirmed after PET CT. Most frequent IRAE were thyroiditis 8/43 (19%), sarcoid-like reaction 8/43 (19%), and colitis 8/43 (19%), with the majority, 25/43 (58.1%) corresponding to grade 2 according to the Common Terminology Criteria for Adverse Events (CTCAE). Most true positive IRAE, 31/43 (72.1%) presented while receiving single-agent therapy, mainly nivolumab.

Conclusions: ¹⁸F-FDG PET/CT has a high sensitivity and specificity for the detection of IRAE in patients with metastatic melanoma under immunotherapy and can detect subclinical IRAE in up to 32% of cases with significant implications for patient management.

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