Effect of neoadjuvant chemotherapy on [⁶⁸Ga]Ga-FAPI-46 PET/CT in peritoneal carcinomatosis: a prospective...

To evaluate whether [⁶⁸Ga]Ga-FAPI-46 PET/CT (FAPI PET) is sensitive to neoadjuvant chemotherapy (NAC)-associated changes in peritoneal carcinomatosis (PC) and whether post-NAC FAPI PET parameters and pre-/post-NAC changes are associated with histopathologic and biochemical response.

This exploratory translational sub-cohort analysis was conducted within the prospective phase II FAPeCa trial (NCT06061874) recruiting patients with colorectal or ovarian cancer with known/suspected PC. Patients who received recent chemotherapy were included in the current analysis. PET parameters, including SUVmax, peritoneal tumour volume (PTV), and total lesion uptake (TLF/TLG) were analysed both on FAPI and [¹⁸F]-FDG PET/CT. Associations with pathological chemotherapy response score (pCRS) and CA-125 change were explored. Pre- and post-NAC paired FAPI PET and FAP immunohistochemical (IHC) analyses were performed. Segment-level correlation between IHC score and FAPI PET uptake was assessed.

Twenty-seven patients were included, predominantly with ovarian cancer (26/27), including 10 with paired pre-/post-NAC imaging. All paired FAPI PET parameters declined significantly after NAC. The magnitude of change in paired FAPI PET parameters correlated strongly with pCRS, particularly for SUVmax (ρ=0.866, p=0.005), PTV(2.5) (ρ=0.830, p=0.011), and TLF(2.5) (ρ=0.830, p=0.011), whereas FDG PET parameters and FAPI PTV(40) and TLF(40) showed no significant correlation with pCRS. Changes in FAPI PET parameters also correlated with the CA-125 change. Across the post-NAC cohort, FAPI PET volumetric parameters differed significantly across pCRS categories. Paired IHC demonstrated a significant reduction in FAP expression after NAC, and segment-level FAP IHC score showed a significant moderate correlation with FAPI uptake (SUVmax ρ=0.467, p=0.012; SUVmean ρ=0.554, p=0.005).

[⁶⁸Ga]Ga-FAPI-46 PET/CT demonstrated treatment sensitivity after NAC in PC, with concordant reductions in PET parameters and stromal FAP expression. FAPI PET volumetric parameters were associated with histopathologic response and CA-125 change in this exploratory sub-cohort, supporting further investigation of FAPI PET as an imaging biomarker for response assessment in PC.