Exploring Endovascular Photo-Activated Ablation (EPA) for Downstaging Locally Advanced Pancreatic Cancer: A Proof-of-Concept Study in the Normal Porcine Model

Abstract

Background: Pancreatic cancers can involve large blood vessels early, making complete resection technically challenging or impossible. A minimally invasive treatment that clears vessels from encasing tumours could potentially enable curative surgery. We hypothesise that Endovascular Photo-activated Ablation (EPA) of perivascular tumour tissue can create a necrotic zone free of viable tumour between cancer and blood vessels, through which the tumour could be resected. Methods: A dose escalation study was conducted in the normal porcine model (n = 7). Under general anaesthesia, the animals were given a photo-activated drug and photo-activation was provided by a prototype balloon catheter, positioned in a major blood vessel within the pancreas, under angiographic guidance. Contrast-enhanced CT scans were undertaken prior to and 1, 2, or 7 days following ablation. The animals were euthanised and the exposed tissue excised en bloc for histological examination. Results: Five animals were euthanised after 2 days. On post-mortem, the histology confirmed necrotic pancreas in the perivascular zone, which increased from zero to 15 mm around the treated vessel, for increasing drug doses. Treated arteries showed necrotising arteritis, without evidence of perforation or obstruction during the observation period, although one animal was euthanised at 1 day, due to technical endovascular device issues and obstruction. The lowest-dose animal euthanised at 7 days showed no lesions on pathology. Conclusions: These proof-of-concept results demonstrate that EPA can produce pancreatic perivascular necrosis in a large animal model. In a pancreatic cancer abutting a major blood vessel, this procedure may be able to create a zone free of viable tumour, potentially rendering these cancers operable, while preserving vessel integrity. These findings support further research activities towards clinical translation.