Title: Detection of metastatic axillary sentinel lymph nodes using ultrafast, super-resolution, dual-contrast enhanced ultrasound imaging in patients with breast cancer
Funder: Department of Health and Social Care

Abstract: Background Every year, 46,000 people are diagnosed with invasive breast cancer in the UK. It is important to know if the cancer has spread to armpit lymph nodes because this may change the type of treatment offered. Currently, the best way to find cancerous lymph nodes is to remove them to check for cancer deposits (metastases). Surgery is necessary because, at present, there are no imaging tests reliable enough to replace the operation. Only 1/3 will have lymph node metastases so 32,500 patients are having unnecessary surgery costing the NHS around &pound;26 million/ year. Armpit surgery causes arm swelling in 1/20 patients who have a small number of sentinel nodes removed and 1/4 who have all their lymph nodes removed. Aims and objectives This research aims to develop a prototype ultrafast, super-resolution contrast enhanced ultrasound system (software and hardware), that can be added to existing ultrasound machines, to replace armpit surgery as a test to find sentinel lymph node metastases in breast cancer patients. Methods A fast/ real-time 3-D imaging system for armpit sentinel nodes will be developed and optimised (WP1 - 20 patients recruited) during the first 18 months. The prototype will be validated and a preliminary test accuracy study conducted (WP2 - 40 patients recruited) 18 to 30 months. Stakeholder analysis, pathway mapping, impact evaluation, human factors studies and health economic evaluation will run alongside WP1 and WP2. Imperial Innovations will help develop commercialisation strategies. Anticipated impact and dissemination The technology developed in this project has the potential to completely replace surgical excision of lymph nodes for 32,500 patients/ year. The prototype system may also directly translate to the management of other cancers such as skin and head and neck. Patient associates will help disseminate the results in addition to presentation and publication in meetings and peer-reviewed journals.

Lay abstract: Invasive breast cancer affects 46,000 people every year in the UK. Cancerous cells can spread to armpit lymph nodes through tissue fluid channels and patients may need more extensive treatment if cancer deposits (metastases) are found. Currently, the best way to find cancerous lymph nodes is to surgically remove them and look for metastases. Armpit surgery is necessary because there are no radiology tests reliable enough to replace the operation. Most armpit surgery involves the removal of sentinel nodes, which are the first lymph nodes to receive tissue fluid from the breast. If clear of cancer, the rest of the armpit lymph nodes are also likely to be cancer free. Sentinel node removal can cause wound infections (1/10) and long-term arm swelling (1/20). As less than 1/3 of patients have metastases in lymph nodes, about 32,500 patients have unnecessary surgery every year costing the NHS &pound;26 million. Almost 80% of women survive breast cancer and dealing with life-long complications puts a strain on them and their families. The aim of this research is to develop a new ultrasound test to replace armpit surgery and the idea came from front-line clinical staff and patients living with problems caused by armpit surgery. This research is a partnership between biomedical engineers at Imperial College London, a breast surgeon and pathologist in Kent and radiologists in London and Kent. The London iVD cooperative, lay advisors and statistical experts are also part of the team. The new ultrasound test builds on technology developed at Imperial College and combines it with studies pioneered at Maidstone using tiny gas filled microbubbles (contrast) injected into the breast to identify sentinel nodes using ultrasound in cancer patients. The current contrast ultrasound test has problems with reliability and sometimes fails whereas the new technology promises to more precise and better able to detect whether sentinel nodes contain metastases. In animal experiments, the advanced technology can even make out microscopic structures inside lymph nodes. The i4i grant is required to develop a contrast ultrasound package (made up of software and equipment) that can be used with ultrasound machines in the breast clinic for armpit scanning. Sixty breast cancer patients will be recruited for the clinical studies, which are designed to ensure the new ultrasound test can find sentinel node metastases as well as being easy to use, safe, comfortable and cost effective for the NHS. The creation of a contrast ultrasound test to replace armpit surgery promises to improve the quality of life for patients and be cheaper than an operation. If successful, this research will lay the foundation for a larger clinical study to prove that the new ultrasound test finds sentinel node metastases as accurately as armpit surgery.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS