Imaging of Tumor Stroma Using ⁶⁸Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial

Abstract

The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of ⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) PET/CT compared with ¹⁸F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24–76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. ⁶⁸Ga-FAPI PET/CT detected more primary lesions than ¹⁸F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, ⁶⁸Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with ¹⁸F-FDG PET/CT. The Kaplan–Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86–17.94; P = 0.0097). Conclusion: ⁶⁸Ga-FAPI PET/CT outperforms ¹⁸F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients.