Predictive value of baseline 68Ga-FAPI PET/CT in the first-line therapy of pancreatic ductal adenocarcinoma (PDAC).

e16300 Background: This study aimed to explore whether parameters from the baseline 68Ga-fibroblast activating protein (FAP) inhibitor (FAPI) PET/CT could predict outcomes in PDAC patients receiving first-line treatment based on a Phase II clinical trial (previously reported in 2023 ASCO, abstr 4142 and 2024 ASCO-GI, abstr 671). Methods: Patients underwent 68Ga-FAPI PET/CT scan before the first dose of first-line treatment of NASCA (nab-paclitaxel, S-1, surufatinib, and camrelizumab) or GnP (nab-paclitaxel and gemcitabine) regimen were enrolled. The parameters of 68Ga-FAPI-04 PET/CT, including SUVmax, SUVmean, target-to-background ratio (TBR) (background including liver, muscle, and blood pool), and FAP expression tumor volume (FTV) of each tumor lesion, were recorded. The highest SUVmax, SUVmean and TBR (H-SUVmax, H-SUVmean, H-TBR), and summed FTV in each region (primary tumor, liver, peritoneal, lymph nodes, lung and bone) and whole body (WB) were also evaluated. Results: From January 2022 to July 2023, a total of 28 out of 42 patients were enrolled. Nineteen patients had received the NASCA regimen, and 9 patients had received GnP regimen. The SUVmax of primary site and metastatic sites were 16.46 (7.56-28.03) and 7.83 (2.13-19.22), respectively. The SUVmean of primary site and metastatic sites were 9.24 (4.05-14.99) and 4.63 (1.44-11.25), respectively. Both the SUVmax and SUVmean of primary site were significantly higher than that of metastatic sites (P < 0.001). 68Ga-FAPI PET/CT showed higher sensitivity in detecting metastases than CT/MRI, especially peritoneal metastases. Only 30% (3/10) of patients were diagnosed with peritoneal metastases by CT/MRI. The ROC curve and AUC for the H-SUVmax, H-SUVmean, and summed FTV in WB or each region were evaluated by separating patients into responders and non-responders. H-SUVmax-WB had the highest AUC for predicting treatment response with a cut-off value of 18.2. Patients with H-SUVmax-WB below 18.2 had significantly longer progeression-free survival (PFS) than those above [8.8 months vs 3.8 months, P = 0.026, HR = 0.30, 95%CI (0.10-0.87)]. However, H-SUVmax-WB was not a prognostic factor (P = 0.292). Among H-TBRblood, TBRmuscle and TBRliver, H-TBRblood-WB (25.9 as the cut-off) was the most pronounced predictive (P = 0.001) and prognostic factor (P = 0.039). The trend of differences in PFS continue exists both in NASCA (p = 0.047) and GnP group (p = 0.018). The multivariable analysis revealed that H-TBRblood-WB (P = 0.026) and liver meatastases (P = 0.026) were independent predictive factors. Conclusions: The highest TBRblood of tumor lesions on 68Ga-FAPI PET/CT was associated with poor response in first-line treatment of PDAC. The utility of 68Ga FAPI PET/CT before treatment could reflect the tumor burden and may predict the response of therapy. For those with high uptake of FAPI, therapy targeting FAP might have a promising future.