Title: Implantable Lymph Node Substitute for Prevention of Surgically-Induced Lymphoedema
Funder: Department of Health and Social Care

Abstract: Lymphoedema is a common adverse side-effect of cancer surgeries performed in the NHS. Most commonly, it causes an incurably swollen arm in breast cancer patients, leading to a lifetime of disability, disfigurement and mental health issues. Caring for these patients (compared to breast cancer patients who do not develop lymphoedema) is estimated to cost the NHS &pound;1344m per year. There are currently no treatments available for this condition, but there are pharmaceutical strategies in clinical trials. We have developed a permanent implant that would be deployed at the time of surgery to reconnect lymphatic vessel pathways disrupted by cancer surgeons. The implant is designed to replicate the fluid mechanical characteristics of natural lymph nodes, and will elute a growth factor specific to lymphatic vessel cells (VEGFC). The proposed three-year development project will take the implant from early feasibility studies (we have demonstrated success with early-stage in vivo research) to being fully ready for subsequent preclinical testing in vivo. This requires strict adherence to regulatory-compliant design and testing procedures. We will develop Standard Operating Procedures for all aspects of implant manufacturing and testing. This will include development of sterilisation procedures, determination of implant shelf life, and finalisation of design details (mechanical stability and optimisation of VEGFC release kinetics). We will also update our existing business plans, which will include externally supplied analyses of Freedom-to-Operate, Health Care Economics, Regulatory Compliance, and Trial Design. Following the proposed project, we will pursue separate funding for preclinical and clinical trials. While the challenges to bringing a permanently implantable medical device to the market are considerable, the proposed work presents an opportunity to prevent adding to the total of 168,000 women in England currently living with incurable lymphoedema.

Lay abstract: Nearly all cancer deaths are due to the spread of the cancer to another part of the body such as the brain or lungs. The cancer travels there through the lymphatic system, which is a network of small tubes that pump fluid from the various parts of your body back into the blood vessels in your shoulders. The cancer flows along with this fluid and then the blood to the brain or lungs. The lymphatic system includes small filters called lymph nodes that are supposed to catch the cancer and remove it. During cancer surgeries, doctors look at the lymph nodes and remove them if they contain cancer in order to minimise the risk of the cancer spreading. For breast cancer patients, this means removing lymph nodes in the armpit, which also filter fluid coming from the arm. While this does help prevent the spread of cancer, it often interrupts the flow of fluid out of the arm, causing the arm to swell. Approximately 1 in 5 breast cancer patients end up with a permanently swollen arm, a disease called lymphoedema. This condition is incurable, and disables the patient for life. We have developed an implantable device that would be placed in the armpit at the time of surgery to re-establish connections with the injured lymphatic vessels. The implant s design is inspired by your own lymph nodes to encourage fluid flow, and is made from the same materials used in safe, everyday devices such as sutures. Our tests indicate that the device is successful, and now we propose to prepare the device for further testing in humans. We have applied for a patent for the device and our aim is to start a company that provides the device to hospitals where cancer surgeries are performed. We have presented the problem of lymphoedema at an Imperial Science Caf&eacute; where patients agreed on the seriousness of living with lympoedema. We have several enthusiastic lymphoedema patients from the Imperial Patient and Public Involvement Group involved in this project. We plan on recruiting more women from our lymphoedema service and through the Cancer Research UK s Your Involvement Network with the help of their Senior Patient Involvement Officer, who is responsible for supporting researchers with patient involvement. A group of 6-8 women will form an advisory group that will follow this study from design, to management and dissemination of findings. We will offer patient reps training through the NIHR BRC PERC in-house PPI courses and engage them in other outreach activities. One of the problems with trying to treat lymphoedema is that not many clinicians understand how the lymphatic system works, so we will target healthcare worker education as well.

Research activity codes: 5.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS;CARDIOVASCULAR