12204 Role Of [18F]FDG-PET/CT In Detection Of Immunotherapy-induced Hypophysitis - A Case-control Study
Authors: Fischer A , Martinez Gomez J M , Mangana J , Dummer R , Erlic Z , Nölting S , Beuschlein F , Maurer A , Messerli M , Huellner M W , Skawran S 
Published: October 2024

Abstract
Disclosure: A. Fischer: None. J.M. Martinez Gomez: None. J. Mangana: None. R. Dummer: None. Z. Erlic: None. S. Nölting: None. F. Beuschlein: None. A. Maurer: None. M. Messerli: None. M.W. Huellner: None. S. Skawran: None.
Adverse events related to immune-checkpoint inhibitor (ICI) therapy frequently affect endocrine organs. Depending on the type of ICI therapy, 0.5% to 10% of patients develop hypophysitis. Diagnosis relies on unspecific clinical symptoms and low serum cortisol level. On MRI, the diagnosis of ICI-induced hypophysitis is supported by enlargement of the pituitary gland and its stalk. However, pituitary MRI is negative in up to 2/3 of patients with hypophysitis on anti-PD-1 monotherapy. A delayed diagnosis increases the risk for life-threatening adrenal crisis. Consequently, there is a need for diagnostic tools that facilitate the early detection of ICI-induced hypophysitis. In this retrospective, single-center case-control-study, we investigated the diagnostic efficacy of [[1]8F]FDG positron emission tomography/computed tomography (FDG-PET/CT) in detecting ICI-induced hypophysitis. Fourteen patients with metastatic melanoma and ICI-induced hypophysitis were compared to a control group of 14 metastatic melanoma patients undergoing ICI treatment without evidence of hypophysitis, matched for age and sex. FDG-PET/CT scans were acquired as part of routine clinical care between 79 days before to 8 days after hypophysitis diagnosis (mean 26+/-29 days before diagnosis) in the case group. In the control group, FDG-PET/CT scans were obtained at a mean of 78+/-31 days after initiating ICI therapy. To mitigate inter-individual differences in standardized uptake value (SUV), the ratio of maximum SUV of the pituitary gland to the mean SUV of the blood pool (SUV-ratio pituitary/bloodpool) was calculated. Hypophysitis was diagnosed at a median of 83 (range: 65 - 98) days after the first ICI treatment; 9/14 (64.3%) patients received ipilimumab/nivolumab. Isolated cortisol deficiency was observed in 6/14 patients (42.9%), while 7/14 (50.0%) patients also displayed secondary hypothyroidism. Visual assessment of the distribution of the SUV-ratio pituitary/bloodpool demonstrated a positive correlation with decreasing proximity to the time of diagnosis. To evaluate diagnostic performance, only patients within 50 days before and 8 days after diagnosis (12/14) were included. The SUV-ratio pituitary/bloodpool was significantly higher in the case group compared to the control group (mean 3.57+/-3.24 vs. 1.69+/-0.41 respectively; p = 0.034). By optimizing the Youden index through area under the receiver operating characteristics curve (AUC) analysis, a sensitivity of 72.7% and a specificity of 90.9% were achieved at a threshold of 2.41 for the SUV-ratio pituitary/bloodpool (AUC = 0.769). In conclusion, our findings indicate that in patients undergoing ICI treatment for metastatic melanoma, an pituitary SUV-ratio pituitary/bloodpool in FDG-PET/CT of approximately 2.5 might indicate impending ICI-induced hypophysitis and should trigger close clinical monitoring.
Presentation: 6/3/2024