Endovascular Transcatheter Photodynamic Ablation to Downstage Locally Advanced Pancreatic Cancer Followed by Surgery: A Proof-of-Concept Study in a Porcine Model

Background Pancreatic cancers can involve large intrapancreatic blood vessels early, making complete tumour resection technically challenging or impossible for surgeons. A minimally invasive treatment that clears vessels from encasing tumours is needed so more patients may undergo curative surgery. We hypothesise that effective ablation of perivascular tumours is possible through endovascular transcatheter photodynamic ablation (PDA). Methods Utilising in silico Monte Carlo calculations, the known needle-based photodynamic dose responses from previous Phase I/II studies were converted to endovascular transcatheter-based energy delivery. Subsequently, an in vivo dose escalation study in the porcine pancreas (n = 7) was performed utilising a prototype ablation catheter developed as part of this study. Results The simulations determined the recommended phase 1 PDA dose ranges to produce a 4, 8, or 12 mm margin of perivascular necrosis. In the porcine pancreas model, increasing doses produced increasingly large perivascular necrotic margins (0-15mm) while the vessel maintained its integrity for up to 7 days post-ablation, as determined by CT imaging and histopathology. Conclusions These proof-of-concept results demonstrate endovascular transcatheter PDA can produce adequate perivascular necrosis in a large animal model while preserving vessel integrity, justifying further investigation in Phase I/II clinical studies.