Prognostic Value of Fibroblast Activation Protein–Directed PET Imaging in Pleural Mesothelioma

Résumé fourni par la source

High expression of fibroblast activation protein (FAP) has been associated with inferior survival in several tumor entities. Novel 68Ga-radiolabeled FAP inhibitors (68Ga-FAPIs) allow noninvasive measurement of FAP, which enables the development of prognostic imaging parameters from 68Ga-FAPI PET/CT. In this study, we compared the prognostic value of 68Ga-FAPI-46 with 18F-FDG PET in a cohort of patients with malignant pleural mesothelioma from the FAPI PET observational trial (NCT04571086). Methods: Between May 2020 and January 2024, 49 patients with suspected or proven malignant mesothelioma were recruited, 39 of whom were eligible for data analysis. All patients underwent 68Ga-FAPI-46 and 18F-FDG PET/CT less than 4 wk apart. Tumor burden was measured semiautomatically, and SUVmax, SUVmean, and volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis/total lesion fibroblast activation, and total tumor SUV) were calculated. The FAP immunoreactive score (IRS) was calculated for tumor samples from a subset of patients (n = 19). Overall survival and progression-free survival were assessed per revised mRECIST (version 1.1). Survival analyses were performed with univariate and multivariate Cox regression and with Kaplan–Meier curves for clinical and imaging parameters, stratified by median. Results: Univariate analysis showed significant survival differences for all volumetric parameters for 68Ga-FAPI-46 and 18F-FDG (e.g., 68Ga-FAPI-46 MTV, 262 d vs. 737 d; P = 0.008 vs. 18F-FDG MTV, 336 d vs. 760 d; P = 0.012). Multivariate analysis revealed that MTV was an independent prognostic marker for 68Ga-FAPI-46 (hazard ratio, 4.44; 95% CI, 1.20–16.43; P = 0.025) and 18F-FDG (hazard ratio, 7.01; 95% CI, 1.29–38.2; P = 0.024). Kaplan–Meier analysis of the FAP IRS found that a higher IRS was associated with poorer survival (438 d with an IRS of 0–3 vs. 1,076 d with an IRS of 4–12; P = 0.04), but no significant difference was observed in univariate and multivariate analyses. Conclusion: In this modest exploratory cohort of patients with malignant pleural mesothelioma, MTV determined by 68Ga-FAPI-46 and 18F-FDG PET/CT had similar prognostic value, and high MTV was an independent risk factor. 68Ga-FAPI-46 not only complements a diagnostic work-up but also provides prognostic value and could offer alternative theranostic strategies for these patients.

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