Doughnut-shaped bone lesions on 18F-FDG-PET/CT may indicate pseudoprogression under immuno(radio)therapy

PURPOSE: Pseudoprogression (PP) is rarely observed in the skeleton. Over the past years, we have observed the appearance of unclassifiable, doughnut-shaped bone lesions in patients under immunotherapy. Our study aims to characterize these lesions under the hypothesis they may represent osseous PP. METHODS: This retrospective study included 714 patients under immune-checkpoint inhibitor (ICI) therapy, targeted therapy, chemotherapy or local radiotherapy (RT) for either malignant melanoma (mM), lung cancer (LC), oropharyngeal or nasopharyngeal cancer with annular bone lesions, who underwent 18F-fluorodeoxyglucose positron emission tomography / computed tomography (18F-FDG-PET/CT) at the University Hospital Zurich between January 2010 and November 2023. Characteristics of annular bone lesions, including 18F-FDG-PET/CT metrics, were recorded. A descriptive analysis was carried out. RESULTS: Six of the 714 patients demonstrated a new onset of 18F-FDG-avid doughnut-shaped bone lesions on 18F-FDG-PET/CT. Five patients were under ICI therapy and one patient was under RT. All lesions were transient and resolved on follow-up imaging. In two of six patients, histopathology samples were obtained and excluded malignancy. All ICI-treated patients demonstrated high 18F-FDG uptake of the lesions without corresponding abnormalities on computed tomography (CT). The mean time to lesion appearance after therapy initiation was 10.0 ± 8.1 months, and mean resolution occurred 7.7 ± 2.4 months after detection. All patients under ICI therapy exhibited additional immune-related changes. CONCLUSION: New, metabolically active doughnut-shaped bone lesions without clear CT correlates on 18F-FDG-PET/CT in patients receiving immunotherapy (or local RT) likely represent benign manifestations within the spectrum of PP rather than metastatic disease.