Endoscopic ultrasound-guided fiducial marker placement for image-guided proton beam therapy in pancreatic cancer: implications for positional accuracy and position management.

High geometric precision is essential in proton beam therapy (PBT) for pancreatic cancer. This study evaluated inter-fraction positional accuracy during image-guided PBT using radiopaque surrogates and assessed endoscopic ultrasound-guided fiducial marker placement (EUS-FP). Patients with pancreatic cancer treated with PBT between 2020 and 2024 were retrospectively reviewed. The positional accuracy cohort included 58 patients with a radiopaque surrogate (fiducial marker group, n = 46; biliary stent group, n = 12). Major positional deviation was defined as a couch displacement ≥5 mm after bony alignment. Factors associated with major positional deviation were analyzed using generalized estimating equations. Oncologic outcomes were analyzed in patients with unresectable locally advanced (UR-LA) pancreatic cancer receiving concurrent chemoradiotherapy (n = 27). EUS-FP was technically successful in 45/46 patients (98%), with mild adverse events in 13%. Major positional deviation occurred in 18.5%, 30.9% and 11.2% of setups in the left-right, cranio-caudal and antero-posterior directions, respectively. Tumor location and disease status were independently associated with major positional deviation, whereas surrogate type was not. Pancreatic head tumors showed a higher risk than tail tumors, while UR-LA cases demonstrated greater positional stability. Overall survival from diagnosis did not differ significantly between surrogate groups; the median follow-up was 14.9 months. These findings indicate that positional deviation during PBT is primarily driven by tumor-related characteristics rather than the type of radiopaque surrogate used for image guidance. Although biliary stents may serve as radiopaque surrogates in selected cases, EUS-FP is a safe and reproducible technique enabling image-guided PBT.