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. 2024 Dec 1;49(12):e656-e663.
doi: 10.1097/RLU.0000000000005440. Epub 2024 Sep 25.

18 F-FDG PET/CT for Detection of Immunotherapy-Induced Hypophysitis-A Case-Control Study

Alessa Fischer, Julia M Martínez-Gómez, Joanna Mangana, Reinhard Dummer, Zoran Erlic, Svenja Nölting, Felix Beuschlein, Alexander Maurer, Michael Messerli, Martin W Huellner, Stephan Skawran

18 F-FDG PET/CT for Detection of Immunotherapy-Induced Hypophysitis-A Case-Control Study

Alessa Fischer et al. Clin Nucl Med. .

Abstract

Purpose: Hypophysitis occurs in up to 10% of patients treated with immune-checkpoint inhibitors (ICIs). MRI shows no abnormalities of the pituitary gland in one third of patients. A delayed diagnosis increases the risk for life-threatening adrenal crisis, underscoring the need for early detection. This study evaluates the diagnostic accuracy FDG PET/CT in detecting ICI-induced hypophysitis in a cohort of melanoma patients.

Materials and methods: Patients with metastatic melanoma and ICI-induced hypophysitis, who underwent FDG PET/CT 90 days before to 10 days after diagnosis, were compared with an age- and sex-matched control group of patients undergoing ICI treatment without signs of hypophysitis. The ratio of SUV max of the pituitary gland to the SUV mean of the blood pool (target-to-background ratio [TBR]) was calculated. Diagnostic accuracy of the TBR was assessed using area under the receiver operating characteristics curve analysis.

Results: A total of 28 patients was included. The majority of patients with hypophysitis received ipilimumab/nivolumab (64.3%, 9/14). Visual assessment of the TBR distribution demonstrated a positive correlation with decreasing time to diagnosis. To evaluate diagnostic performance, only patients with FDG PET/CT 50 days before to 8 days after diagnosis (11/14) were included. TBR was significantly higher in these compared with the control group (median [interquartile range], 2.78 [2.41] vs 1.59 [0.70], respectively; P = 0.034). A sensitivity of 72.7% and a specificity of 90.9% were achieved at a TBR threshold of 2.41 (area under the receiver operating characteristics curve = 0.769).

Conclusions: Our findings suggest that, in patients undergoing ICI treatment for metastatic melanoma, a pituitary TBR of approximately 2.4 may indicate impending ICI-induced hypophysitis.

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Conflict of interest statement

Conflicts of interest and sources of funding: Dr Stephan Skawran is supported by a grant from the Iten-Kohout Foundation, Switzerland and the Palatin-Foundation, Switzerland. Dr Alessa Fischer is supported by a research grant from the “Young Talents in Clinical Research” program of the SAMS and of the G. & J. Bangerter-Rhyner Foundation, Switzerland. Dr Michael Messerli received a research grant from the Iten-Kohaut Foundation, Switzerland. Dr Michael Messerli and Dr Martin W. Huellner are supported by a grant from the CRPP AI Oncological Imaging Network of the University of Zurich. Dr Martin W. Huellner received grants from GE Healthcare and a fund by the Alfred and Annemarie von Sick legacy for translational and clinical cardiac and oncological research. The melanoma registry database of the Department of Dermatology, University Hospital Zurich has been partially supported by an unrestricted grant to the University of Zurich from Amgen, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre. The University Hospital of Zurich holds a research agreement with GE healthcare (unrelated to current study). Joanna Mangana has intermittent project focused consultant or advisory relationships with Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, and Pierre Fabre and has received travel support from L’Oréal, Merck Sharp & Dohme, Bristol Myers and Squibb, und Pierre Fabre outside of the submitted work. Other than that, the authors declare that they have no competing interests.

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