The FAP-FDG Integration Score (FFIS): Development and prognostic validation of a dual-tracer PET phenotype for solid tumors.

Abstract

To develop a FAP-FDG integrated score (FFIS) based on [⁶⁸Ga]Ga-FAP-2286 and [¹⁸F]F-FDG PET/CT, and evaluate its prognostic value for risk stratification compared to conventional single-parameter imaging. This retrospective study included 193 patients with solid tumors who underwent both [¹⁸F]F-FDG and [⁶⁸Ga]Ga-FAP-2286 PET/CT scans. Overall survival (OS) was the primary endpoint. The FFIS score was constructed by analyzing the uptake intensity and patterns of both radiotracers. Survival analysis employed the Kaplan-Meier method. The prognostic predictive value of FFIS, FDG-SUVmax, and FAP-SUVmax was evaluated using univariate and multivariate Cox proportional hazards models and compared with other clinical variables. Finally, subgroup analysis and interaction tests explored the prognostic consistency of FFIS, FDG-SUVmax, and FAP-SUVmax across different subgroups. FFIS emerged as an independent predictor of OS in both univariate (HR = 1.79, P < 0.001) and multivariate (HR = 1.75, P < 0.001) analyses. A higher FFIS reliably predicted worse survival: no deaths occurred among patients of score 1, whereas the median OS was 36, 13, and 8 months for scores 2, 3, and 4, respectively (Log-Rank P < 0.0001). This prognostic stratification remained consistent nearly all clinical subgroups (P-interaction > 0.05). In contrast, FDG-SUVmax showed no independent prognostic value, and FAP-SUVmax was predictive only in univariate analysis (HR = 1.04, P = 0.03). By integrating metabolic and stromal information, the FFIS may offer preliminary prognostic value across solid tumors.