UFOGUIDE : Burning bone tumors with focused ultrasound

The most common cancers (breast, prostate, lung, colon) are very often associated with the appearance of secondary tumors, known as metastases. In particular, these can reach the bones, entailing serious risks for the patient's health, as well as pain that is generally very intense.

Thanks to advances in medicine, life expectancy for cancer sufferers is increasing. While this is obviously good news, it also means that these individuals have to live longer with painful, even incapacitating bone tumors. So it's vital that we find solutions to help these patients.

Ultrasound therapy: an effective, non-invasive, well-tolerated treatment, but too expensive?

What therapies are possible today? Only palliative treatments can be envisaged, such as the use of morphine derivatives, which have serious side effects. What about radiotherapy? " This treatment generally works well, but its efficacy is limited in duration and it cannot be repeated indefinitely due to its ionizing nature," warns Jonathan Vappou, a CNRS researcher at the ICube laboratory.

Another particularly effective solution is thermal ablation treatment, using focused ultrasound. " To illustrate this, imagine using a magnifying glass to burn a leaf," explains the researcher. " The principle is to focus the energy of the sun's rays to produce a very localized burn at the focal point. We use the same process, but replace the light source with ultrasonic waves, which provide the acoustic energy, directed towards the focus. " The advantage of this method is that it concentrates the therapeutic effect solely on the localized area, without burning adjacent areas or the skin. What's more, it's a non-invasive, non-ionizing treatment, so doses can be multiplied as required.

The technique is not new, however, as Jonathan Vappou explains: " There are already a number of systems that use ultrasound therapy to treat bone tumors. The problem is that these devices are extremely expensive and cumbersome to install. They can be effective in certain cases, but their use is unfortunately limited depending on where the tumor is located.

The challenge, for example, is to make ultrasound treatment of bone tumors easier to perform, cheaper to implement and therefore much more accessible. A need expressed in 2013 by the director of the interventional imaging department at Strasbourg University Hospitals. To meet this need, a collaboration began between the ICube laboratory, represented by Jonathan Vappou, and the company Image Guided Therapy, headed by Erik Dumont, with the help of Axilum Robotics and the support of Carnot TSN. "According to the CNRS researcher, " This is a 100% technological collaboration between partners working as equals.

MRI, an additional challenge

From the outset of the project, the ambition was to break with the usual practice of ultrasound therapy for this indication. Until now, it was necessary to position the patient in the right place on the operating table, at the level of a narrow window allowing treatment, which proved complicated, if not impossible in some cases. The research team's innovative approach consisted, instead, in bringing the transducer (emitting the ultrasound waves) directly to the spot to be treated. A real challenge, since, unlike in open surgery, the doctor cannot see the area he is operating on.

Another major constraint was included in the researchers' specifications: operations had to be carried out under MRI (magnetic resonance imaging) control. An environment that notably excludes any presence of metallic elements! All of which significantly complicated the task of the study's authors. But why impose this constraint? " In theory, there are other possibilities, such as ultrasound imaging," notes Jonathan Vappou, " but MRI has one big advantage: it allows temperature monitoring. And in our case, it was imperative for the clinicians to have this monitoring in real time. " This temperature control not only ensures that the targeted area exceeds 80°C (the threshold required to obtain the desired clinical effect), but also that the operation does not overheat neighboring tissues, notably the skin or motor nerves.

A leg positioning system

To meet these objectives, the team has developed a positioning system built around a transducer held by four "legs". Each leg consists of a latex chamber filled with inexpensive polypropylene beads. " This construction gives these elements great flexibility," emphasizes the CNRS researcher. " But all we have to do is create a vacuum inside these legs to stiffen them and fix their position. " This patent-protected innovation makes it possible to immobilize the transducer once it has been placed by the clinician.

However, it still has to be positioned in the right place. The navigation maneuver takes place in two stages. Firstly, the target to be treated is defined by the clinician in the pre-operative phase, enabling the optimal position of the transducer in relation to the patient to be determined. Then, during the operation, a real-time registration and navigation process is used to reposition the equipment at the previously defined location. This is a meticulous process, which is monitored via MRI to adjust the exact positioning if necessary. In all cases, low-intensity ultrasound test shots are performed to validate tumor targeting, before proceeding with the full operation.

In this way, researchers have developed a modular, flexible system for treating bone tumors. Called UFOGUIDE, it differs from other ultrasound therapies used for this application in that it is more functional, as well as being much cheaper to manufacture. The result of six years' research, to obtain a functional prototype and then launch clinical studies (after obtaining the necessary authorizations from the ANSM).

Success slowed by Covid-19

At the end of 2021, the team was finally able to test its device in real-life conditions, on a patient suffering from lung cancer, resulting in a very large and painful bone metastasis in the forearm. The results were decidedly promising: " The operation lasted two hours and went very well," reports Jonathan Vappou, " The metastasis was more than 80% eliminated, and the patient regained the use of his arm, whereas amputation had been envisaged prior to ultrasound treatment." At the time, the patient's pain rating was 8/10, despite the use of morphine derivatives. Three days after the UFOGUIDE procedure, he rated it at 3/10, with no side effects.

Unfortunately, since this success, the development of the device has come to a halt. To the dismay of the researcher at the ICube laboratory: " These initial trials have to be carried out under general anaesthetic, which requires the presence of specialist anaesthetic personnel throughout the process. And with the Covid-19 pandemic, these professionals were obviously in great demand...".

However, the start of the 2022 academic year looks set to bring good news, with the examination of two new cases that could benefit from focused ultrasound therapy. The collaboration between Jonathan Vappou and the company Image Guided Therapy is therefore continuing, in the form of a joint laboratory created in the summer of 2022 and funded by the ANR. The aim is not only to make improvements to the UFOGUIDE device, but also to develop new therapeutic approaches, such as the use of focused ultrasound for localized drug delivery.