Prognostic Implications of<sup>68</sup>Ga-FAPI-46 PET/CT–Derived Parameters on Overall Survival in Various Types of Solid Tumors
Masao Watanabe, Wolfgang P. Fendler, Hong Grafe, Nader Hirmas, Rainer Hamacher, Helena Lanzafame, Kim M. Pabst, Hubertus Hautzel, Clemens Aigner, Stefan Kasper, Bastian von Tresckow, Martin Stuschke, Sherko Kümmel, Céline Lugnier, Boris Hadaschik, Viktor Grünwald, Fadi Zarrad, Jens T. Siveke, Ken Herrmann, Manuel Weber
Abstract
Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [<sup>68</sup>Ga]Ga-fibroblast activation protein inhibitor (FAPI) (<sup>68</sup>Ga-FAPI)–46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, <i>n</i> = 30; NCT04571086, <i>n</i> = 115). <b>Methods:</b> Within 4 wk, 145 patients underwent <sup>68</sup>Ga-FAPI-46 and [<sup>18</sup>F]FDG (<sup>18</sup>F-FDG) PET/CT. The association between overall survival (OS) and sex, age, tumor entity, total lesion number, highest SUV<sub>max</sub>, and the presence of each nodal, visceral, and bone metastasis was tested using univariate Cox regression analysis. Multivariate analyses were performed for prognostic factors with <i>P</i> values of less than 0.05. <b>Results:</b> In the univariate analysis, shorter OS was associated with total lesion number and the presence of nodal, visceral, and bone metastases on <sup>68</sup>Ga-FAPI-46 PET/CT (hazard ratio [HR], 1.06, 2.18, 1.69, and 2.05; <i>P</i> < 0.01, < 0.01, = 0.04, and = 0.02, respectively) and <sup>18</sup>F-FDG PET/CT (HR, 1.05, 2.31, 1.76, and 2.30; <i>P</i> < 0.01, < 0.01, = 0.03, and < 0.01, respectively) and with SUV<sub>max</sub> on <sup>68</sup>Ga-FAPI-46 PET/CT (HR, 1.03; <i>P</i> = 0.03). In the multivariate analysis, total lesion number on <sup>68</sup>Ga-FAPI-46 PET/CT was an independent risk factor for shorter OS (HR, 1.05; <i>P</i> = 0.02). In patients with pancreatic cancer, shorter OS was associated with total lesion number on <sup>68</sup>Ga-FAPI-46 PET/CT (HR, 1.09; <i>P</i> < 0.01) and bone metastases on <sup>18</sup>F-FDG PET/CT (HR, 31.39; <i>P</i> < 0.01) in the univariate analysis and with total lesion number on <sup>68</sup>Ga-FAPI-46 PET/CT (HR, 1.07; <i>P</i> = 0.04) in the multivariate analyses. In breast cancer, total lesion number on <sup>68</sup>Ga-FAPI-46 PET/CT (HR, 1.07; <i>P</i> = 0.02), as well as bone metastases on <sup>18</sup>F-FDG PET/CT (HR, 9.64; <i>P</i> = 0.04), was associated with shorter OS in the univariate analysis. The multivariate analysis did not reveal significant prognostic factors. In thoracic cancer (lung cancer and pleural mesothelioma), the univariate and multivariate analyses did not reveal significant prognostic factors. <b>Conclusion:</b> Disease extent on <sup>68</sup>Ga-FAPI-46 PET/CT is a predictor of short OS and may aid in future risk stratification by playing a supplemental role alongside <sup>18</sup>F-FDG PET/CT.