Publications

Safety and Feasibility of Repeatable Hepatic Vascular Access Isolation Chemotherapy: A Pilot Study

BACKGROUND: The authors herein describe a novel method of repeatable hepatic isolation using an implantable access system allowing simultaneous control of hepatic arterial and portal flows by multiple endovascular catheters.

PURPOSE: The aim of this study was to assess the feasibility and safety of the system and to compress standard intravenous chemotherapy into 4 weeks of targeted intra-arterial delivery.

METHODS: An arterial access system was implanted to the axillary artery via an anastomosis. Infusions of oxaliplatin were performed biweekly for 4 weeks, using balloon catheters to achieve hepatic isolation and segmental selectivity for 20-25 min. Fifty-seven treatments under general anesthetic were performed in ten patients with inoperable chemotherapy-refractory metastatic colorectal cancer. Systemic, intrahepatic, and hepatic venous pressures were recorded to assess vascular isolation, and platinum levels were measured to assess chemotherapy distribution.

RESULTS: Pressure verified, multiple day-only hepatic vascular isolation infusions were achieved in nine of ten patients, with a single patient receiving multiple hepatic arterial infusions. Positron emission tomography-computed tomography (PET-CT) imaging confirmed partial response in three of ten patients and stable disease in three of ten patients. Systemic toxicity was minimal as all treatment-related gastrointestinal and neuropathic symptoms reported throughout the 4 weeks were grades 1-2.

CONCLUSIONS: Intra-arterial chemotherapy infusions with hepatic vascular isolation can be achieved repeatedly with targeted selectivity and minimal complications using an implantable multicatheter access system. Oxaliplatin infusions over a 4-week period may achieve tumor response in selected patients in the salvage setting. The technique should be further assessed in a phase Ib/II study.

Ann Surg Oncol. 2016 Oct; 23(11):3699-3708. doi: 10.1245/s10434-016-5198-z. Epub 2016 Mar 25. 

Challenges in chemotherapy delivery: comparison of standard chemotherapy delivery to locoregional vascular mass fluid transfer.

Abstract: Standard intravenous chemotherapy delivery to neoplasms relies on simple diffusion gradients from the intravascular to the interstitial space. Systemic perfusion creates untoward effects on normal tissue limiting both concentration and exposure times. Regional intra-arterial therapy is limited by drug recirculation and vascular isolation repeatability and does not address the interstitial microenvironment. Barriers to delivery relate to chaotic vascular architecture, heterogeneous fluid flux, increased interstitial and variable solid tumor pressure and ischemia. To address these difficulties, a delivery system was developed allowing mass fluid transfer of chemotherapeutic agents into the interstitium. This implantable, reusable system is comprised of multiple independently steerable balloons and catheters capable of controlling the locoregional hydraulic and oncotic forces across the vascular endothelium.

Future Oncol. 2018 Mar; 14(7):647-663. doi: 10.2217/fon-2017-0546. Epub 2018 Mar 7.

The Integration of Pharmacology and Pathophysiology into Locoregional Chemotherapy Delivery via Mass Fluid Transfer

Abstract

The prevailing paradigm of locoregional chemotherapy has been centred around delivering chemotherapy as close to the tumour as possible and in some cases incorporating vascular isolation techniques. Strategically, the development of these techniques has been rudimentary without consideration for the interdependencies between macrovascular manipulation and the microvascular effects. This review focuses on how new capabilities offered by recent advances in vascular access technology could be exploited to facilitate the mass fluid transfer (MFT) of anticancer agents to solid tumours. A haemodynamic model of MFT is proposed using the physical laws of fluid flow, flux, and diffusion that describe the microvascular effects anticancer agents may have upon tumours through the manipulation of macrovascular blood flow control. Finally, the possible applications of this technique for several organs are discussed.

J. Control. Release. 2018 Dec; 292:18-28. doi: 10.1016/j.jconrel.2018.10.019. Epub 2018 Oct 19.