The role of a universal vascular access system in locoregional chemotherapy for solid tumours

Since the advent of chemotherapy, much of the progress gained in the treatment of solid tumours has primarily has been brought about by the advancement of drug designs and chemotherapy combinations. However, in advanced cancers the standard route of intravenous systemic delivery is unable to exploit the full potential of even third generation chemotherapeutic agents and as such, the prognosis for these patients remains grim. Alternatively, locoregional chemotherapy (LRC) techniques focused on delivering chemotherapy as close to the tumour as possible have been able to achieve responses where systemic therapy has failed in some cases. Nonetheless, such techniques are limited to specialised centres, associated with high morbidity and mortality, and are generally not repeatable due to limitations in vascular access technologies. The aim of this thesis was to determine whether a universal vascular access device (UVAS) could be developed which could provide general vascular access and facilitate LRC treatments and if so, to assess the potential of the treatment it can facilitate. A design for a UVAS was developed based on an existing transcutaneous access device as well as the clinical requirements deemed necessary to enable LRC treatments. A meta-analysis was carried out of devices with similar features to obtain an understanding of the risks that may accompany the use of such a device. The developed UVAS was then used in 5 patients with critical limb ischaemia in a clinical trial as a general vascular access device. Additionally, a new LRC technique was developed with the UVAS and tested in another clinical trial of 10 patients with colorectal liver metastases. The device related outcomes in both studies demonstrated that the UVAS was able to perform its intended functions safely as a general vascular access device and in facilitating LRC treatments. The LRC technique developed demonstrated promising results (30% response rate) in patients that had previously exhausted all other therapies. The intra-arterial pressures measured and the minimal toxicity (grades I-II) reported is suggestive of the level of manipulation achieved within the liver which could potentially be applied to other organs. A UVAS was successfully designed, developed, and proven to be fundamental in being able to administer a new LRC treatment in the form of minimally invasive, repeatable liver organ isolation chemotherapy. A system with such capabilities provides encouragement for further LRC techniques that were previously considered too burdensome to be properly investigated.