Safety, feasibility, and palliative benefit of HIFU combined with PD-1 inhibitors for elderly patients with advanced pancreatic cancer: a real-world retrospective study

BACKGROUND: Pancreatic cancer remains largely refractory to immune checkpoint inhibitors. High-intensity focused ultrasound (HIFU) may modulate the immunosuppressive tumor microenvironment via immunogenic cell death, yet clinical evidence on HIFU combined with programmed cell death protein 1 (PD-1) inhibitors in elderly patients is scarce. METHODS: This single-center retrospective study enrolled 13 elderly (≥60 years) patients with advanced pancreatic cancer receiving HIFU plus PD-1 inhibitors (January 2017-December 2024). The primary outcome was safety; secondary outcomes included pain relief (numerical rating scale [NRS]; a decrease of ≥2 points considered clinically meaningful), disease control (RECIST 1.1), progression-free survival (PFS), and overall survival (OS). Exploratory analyses comprised a composite risk score (high-sensitivity C-reactive protein, albumin, and CA19-9) and peripheral immune profiling. RESULTS: = 0.0016), with a median NRS reduction of 3.0 points (IQR: 2.0-3.0). Disease control rates were 75.0% (9/12) in the evaluable and 69.2% (9/13) in the intention-to-treat population. Median PFS was 3.2 months (95% CI: 1.9-3.9) and median OS was 3.7 months (95% CI: 2.1-7.2). CONCLUSIONS: In this small cohort of elderly, heavily pretreated patients with advanced pancreatic cancer, HIFU combined with PD-1 inhibitors showed a manageable safety profile and notable pain relief. Prospective validation in larger studies is warranted.