<sup>68</sup>Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the <sup>68</sup>Ga-FAPI PET Prospective Observational Trial
Lukas Kessler, Justin Ferdinandus, Nader Hirmas, Sebastian Bauer, Uta Dirksen, Fadi Zarrad, Michael Nader, Michal Chodyla, Aleksandar Milošević, Lale Umutlu, Martin Schüler, Lars Erik Podleska, Hans‐Ulrich Schildhaus, Wolfgang P. Fendler, Rainer Hamacher
Abstract
<b>Introduction:</b> Bone and soft tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblast. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radio-labelled FAP-Inhibitors (e.g. <sup>68</sup>Ga-FAPI46) have shown high tumor uptake in positron emission tomography (PET) in sarcoma patients. Here we report endpoints of the FAPI-PET prospective observational trial. <b>Methods:</b> Forty-seven patients with bone or soft tissue sarcomas undergoing clinical <sup>68</sup>Ga-FAPI-PET were eligible for enrollment into the FAPI-PET observational trial. Of these patients, 43 patients also underwent <sup>18</sup>F-Fluordesoxyglucose PET (FDG). The primary study endpoint was the association of <sup>68</sup>Ga-FAPI-PET uptake intensity and histopathological FAP-expression analyzed with Spearman’s r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by two blinded readers. <b>Results:</b> Primary endpoint was met and the association between FAPI-PET uptake intensity and histopathological FAP-expression was significant (Spearman’s r = 0.43; <i>P</i> = 0.03). By histopathological validation PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET positive resulting in an SE of 0.96 (95%CI, 0.82-1.00) on a per-patient and 0.94 (95%CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in FAPI- and FDG-PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients FAPI-PET resulted in an upstaging compared to FDG-PET. FAPI-PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss kappa: primary κ = 0.78; local nodal κ = 0.54; distant nodal κ = 0.91; lung κ = 0.86; bone κ = 0.69 and other κ = 0.65). Clinical management changed in 13 (30%) patients after FAPI-PET. <b>Conclusion:</b> We confirm an association of tumoral FAPI-PET uptake intensity and histopathological FAP expression in sarcoma patients. Further, using blinded reads and independent histopathological validation we report high PPV and sensitivity of FAPI-PET for sarcoma staging.