Radiofrequency ablation (RFA), in which heat is used to destroy targeted tissue, has been in common use for decades. First performed in patients as early as the 1930s, the technique has been used to treat everything from atrial fibrillation to varicose veins.
Unsurprisingly, for a technique that can ‘cook’ undesired cells, it is also used extensively within cancer treatment. While it is not generally deployed as the only mode of treatment, it can provide a viable alternative to surgery in certain patients.
The technique is often used to destroy tumours in the lungs, kidneys, liver and bones (both primary tumours and metastases). As well as boasting a similar success rate to surgery, it is quick and minimally invasive, taking around ten to 15 minutes in total.
“Prior to this technology, patients with a tumour would have to have it removed via laparotomy, which would increase the risk to the patient and recovery time as well as extra costs to the healthcare provider,” says Heather Carré-Skinner, head of regulatory affairs at Ablatus Therapeutics.
Unfortunately, it is limited in terms of the size and location of tumours it can treat. However, Ablatus Therapeutics, a spin-out company from the Norfolk and Norwich University Hospital, is hoping to solve this problem with its new Bimodal Electric Tissue Ablation (BETA) technique, which has high billing as a disruptive technology in the field.
The problems with existing devices
In modern RFA devices, a needle is connected to a generator that delivers radiofrequency alternating current (AC). The needle is inserted directly into the tumour under the guidance of a CT scanner or ultrasound, where AC causes ionic excitation of local molecules. The resulting heat ablates the tissue.
As Carré-Skinner explains, when the tumour is being destroyed, the local tissue becomes dehydrated. This increases the impedance and limits the amount of energy that can be delivered.
“It causes the procedure to end prematurely in a phenomenon known as ‘roll-off’, which may result in incomplete ablation,” she says. “RFA devices on the market have tried to innovate around this issue, such as by using an internally cooled needle that delivers the RF power. However, as the needles are single use there is an increased economic burden and none address the issue of tissue desiccation.”
As a result, most RFA systems are limited to tumours that are less than 3cm in size. If roll-off has occurred, and the tumour has not been completely ablated, the cancer may return.
The BETA technology, currently in the preclinical testing stage, is designed to address the problem of roll-off.
“As in RFA, BETA uses Alternating Current to generate the RF power, but critically also applies Direct Current (DC) through the same needle,” says Carré-Skinner. “The addition of DC is a game-changer – it works by drawing water from the surrounding tissue to the site of ablation. This keeps the tissue hydrated and delays roll-off, meaning that larger ablations can be achieved and the patient can receive their intended treatment.”
Unlike devices with an internally cooled needle, BETA does not rely on complex components, and therefore has scope to be good value for money. On top of that, it may open up new therapeutic possibilities. As Carré-Skinner explains, BETA can be viewed as an engine used to improve all aspects of ablation.
“We have developed a range of thin needles that can potentially lead to new treatment indications such as prostate tumours,” she says. “In addition, BETA can synergise with existing devices such as the Medtronic Cool-Tip and Boston LeVeen needle to generate larger still ablations. Collectively, this shows that we can offer a technology that gives more effective treatment with different clinical indications, all at a more competitive price for the healthcare provider.”
The route to the clinic
The BETA technology, invented by Dr John Cockburn and Dr Simon Wemyss-Holden at the Norfolk and Norwich University Hospital, was assigned to Ablatus Therapeutics in October 2015. The company has since made great strides towards commercialisation.
“Between 2016 and 2018 Ablatus received initial seed funding, an Innovate UK grant, and venture capital investment, which has led to a key team being employed to drive the technology forward,” says Carré-Skinner. “Within the last year Ablatus Therapeutics has completed development of the prototype device and has performed significant pre-clinical work to demonstrate the safety and efficacy of our technology.”
Currently, the team is looking to secure additional funding. This will be used to complete development and perform the first in-human studies.
“This will generate fundamental data for successful regulatory submission in the UK and US,” says Carré-Skinner. “Once completed, we will engage with key opinion leaders in the field to drive adoption of our technology in UK/EU and US markets within two to three years.”
The implications for cancer treatment could be significant. Carré-Skinner envisages the technology being rolled out into a wide range of applications, both within oncology and outside it. If the human studies replicate what has been shown in pre-clinical data, the technique will enable larger tumours to be treated more effectively, and may lead to a lower risk of recurrence.
“In addition, due to the competitive price-point of our device, we are also looking to engage with healthcare providers in developing economies in order to bring effective and safe ablation options where it has not been possible before,” she says.