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

## TL;DR

A new technique called EPA may help make previously inoperable pancreatic cancers surgically removable by safely destroying cancer tissue near blood vessels.

## Contribution

Demonstration of a novel endovascular photo-activated ablation technique in a large animal model for pancreatic cancer downstaging.

## Key findings

- EPA successfully induced necrosis in pancreatic tissue adjacent to blood vessels without damaging the vessels.
- The extent of necrosis increased with higher drug doses in the porcine model.
- No vessel perforation or obstruction was observed during the study period.

## Abstract

Pancreatic tumors often grow around major blood vessels, making surgery impossible for about one in three patients. A treatment capable of clearing tumor involvement from these vessels would represent a significant clinical advance. In the normal porcine model, we tested a novel approach that administers a light-activated drug and then delivers laser light from within an artery or vein. We have shown that this technique, called Endovascular Photo-activated Ablation (EPA), can safely kill a thin layer of the pancreas next to a major blood vessel, while preserving the integrity and function of the blood vessel. The concept is that in the case of a pancreatic cancer touching the blood vessel, in suitable patients, EPA could create a zone of dead cancer tissue through which a surgeon could safely separate the main mass of viable cancer from the blood vessel to enable complete removal of the cancer without damaging the blood vessel. Further laboratory studies are required to refine the technique and ensure that there are no long term complications. Provided these go well, pilot clinical studies can be planned relatively soon. If proven to be safe and effective, this approach may convert previously inoperable pancreatic cancer patients into surgical candidates with the potential to extend their survival.

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.