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.