The ESTRO 37 meeting in Barcelona last week saw over 100 companies exhibiting their products on the show floor. The 5401 m2 exhibition included a corner dedicated to start-up companies. Here, we take a look at the innovation being developed by start-ups Neolys Diagnostics, Medical Precision, PhantomX and NU-RISE.
Radiation therapy just got personal
Lyon-based Neolys Diagnostics is developing decision-making tools that allow radiation oncologists to adapt treatment according to the radiosensitivity of an individual patient. The aim is to reduce treatment side effects while optimizing efficacy.
The toxicity of radiotherapy is dependent upon three factors: the dose delivered to cells, the cell environment (such as the presence of chemotherapeutics) and the radiosensitivity of the patient. “For many years, there have been improvements mostly in the first of these factors, but the individual’s radiosensitivity has been completely forgotten,” explained Gilles Devillers, the company’s president and co-founder. “Still today, 20% of patients receiving radiotherapy have side effects.”
To address this shortfall, Neolys Diagnostics currently offers two test systems. The first, RadioDTect, involves a simple blood test that gives results in 4-5 hours. Designed to be performed for every patient, at the cancer centre, the test identifies whether a patient is at risk of experiencing severe side effects or not. “This test reveals whether a patient is radiosensitive, but it doesn’t show to what extent,” Devillers explained.
To create a detailed map of their level of risk, some patients will require the next step – RadioProfile. This high-performance test involves a small skin biopsy and is performed in Expert Labs partnering with Neolys Diagnostics. Within 2-3 weeks, the test will predict exactly which side-effects a patient will have and at what level.
The tests work by examining DNA repair following radiation-induced double-strand breaks. The number of unrepaired versus repaired breaks (among other markers), identified using immunofluorescence analysis, depend upon the function of the ATM protein in the patient and are a reliable indicator of an individual’s radiosensitivity. This allows estimation of the radiation dose that the patient can tolerate without adverse side effects.
Devillers notes that both tests are CE marked and that seven additional clinical trials are ongoing. In the next phase of development, Neolys Diagnostics is developing a decision support system that helps clinicians choose the most suitable treatment for their patient, providing justification for a particular modality, such as proton therapy, for example, or hypofractionation. “We are going to bring the missing part of the radiotherapy toxicity assessment,” said Devillers.
Reference points without the pain
While radiotherapy delivery techniques have undergone enormous advancements in recent years, the reference points used to guide treatment are still created using tattoos. These are painful for the patient and are commonly injected at depths of 2-3 mm, meaning that they remain forever. This permanence can be particularly distressing for patients with several tattoos in prominent locations, such as breast cancer patients, for example.
Dutch start-up Medical Precision has come up with an alternative. Its MPV-16 system, based on technology developed for permanent make-up, uses a tiny needle to inject pigment into the upper dermis. This painless procedure, where the patient just feels the needle vibration, still creates a highly visible skin mark. Importantly, the mark is not permanent and will disappear six months to a year later – or it can be removed immediately using a laser.
The CE-approved device comes with three colour-coded heads, each offering a different injection depth. The smallest-depth needle, for thin skin, penetrates just 0.2 mm into tissue. For darker or thicker skin, a needle that penetrates 0.4 mm can be used. If a permanent mark is required, a 0.7 mm option is available. Even at this depth, the process is still pain free.
As well as being better for the patient, the shallow depth of the mark also confers greater accuracy for patient positioning. “If a tattoo is too deep, it spreads out under the skin,” explained Annelies Maas, the company’s CEO. “Using a depth of 0.7 mm still creates a small dot that doesn’t grow. The mark stays in place, but can also be removed using a laser.”
Earlier this month, Medical Precision partnered with CIVCO Radiotherapy, who will be the distributors for this innovative marking system.
Copying patients into phantoms
PhantomX, a spin-off from Charité – Universitätsmedizin Berlin, has created a novel 3D printing method that can “copy patients into phantoms”. The idea is to create a phantom with exactly the same radiation attenuation as a patient, enabling realistic simulation of their radiation exposure in CT and radiation therapy.
The phantoms are created using a two-step process. First, CT images of the patient’s anatomy are printed in radiopaque ink on paper, with the CT grayscale used to encode radiation attenuation levels. Then the paper images are stacked into a 3D structure and cut to shape. Following this process, a CT scan of the phantom will be identical to that of the patient.
One key application is patient-specific radiotherapy quality assurance (QA). Here, a treatment plan is delivered to the phantom on the linac and the resulting dose is measured. The phantoms can also be used to generate realistic CT and X-ray images, to investigate dose and imaging parameters. Finally, they provide a realistic simulation environment for training of medical staff.
According to project leader Paul Jahnke, the phantoms could be used for all patient treatments. They are, however, particularly relevant for treatments of younger patients, secondary tumours, head-and-neck tumours near organs-at-risk, or patients with comorbidities.
Optical probes enable in vivo dosimetry
NU-RISE of Portugal is developing an in vivo dosimetry system based on fibre-optic probes that are placed inside the patient’s body. The probes monitor the level of radiation that the patient is receiving in real time, helping doctors better target the cancer and protecting patients from unnecessary irradiation. The company’s vision is to provide valuable data in real time for clinical decision support, enabling safer and accurate radiation treatments.
“We are working to solve one of radiotherapy’s problems – to know what happens in the patient in real time,” explained Luís Moutinho, NU-RISE’s founder and CEO. “Our system can precisely measure the amount of radiation delivered to a tiny volume, usually where organs-at-risk are, and compare it with the treatment plan.”
The system uses optical probes, each of which contains at its end a 2 mm section of a material that converts radiation to light. The probes are less than 1 mm in diameter, making them compatible with standard catheters. This makes NU-RISE’s dosimeter a great solution for real-time in vivo dosimetry in brachytherapy, where currently there are no options available. NU-RISE has also developed a novel method to process the resulting optical signal with minimal noise. According to Moutinho, this allows the probes to cost 10-20 times less than other in vivo dosimetry probes.
This lower pricing level enables the probes to be disposable. As such, each probe is provided pre-calibrated, sterilized and bar-coded, such that each fibre can be easily identified via scanning. The system enables up to six probes to be placed and used simultaneously for each treatment.
The company is currently working to CE Mark the device, but the dosimetry system is available for use by NU-RISE’s clinical partnerships and is already being employed in patients. NU-RISE is also looking for new collaborations and applications of its technology.
