Every year in March, the French Society of Neuroscience coordinates Brain Awareness Week in France. This international event, organized in about a hundred countries, aims to raise public awareness of the importance of brain research. It offers researchers the opportunity to share their advances in neuroscience and explain their implications for society. The second week of March is also Cancer Awareness Week. These two health events take place simultaneously and give us the opportunity to highlight brain tumors in children, adolescents, and young adults, the second most common form of cancer in children and particularly difficult to treat.
Imagine for Margo, at the Heart of Innovation to Fight Brain Cancers
Since 2011, Imagine for Margo has been strongly committed to fighting pediatric brain cancers, the leading cause of cancer-related mortality in children and adolescents. High-risk forms, of embryonic origin, are often particularly invasive and difficult to treat, making relapses too often fatal. At Imagine for Margo, we consider the development of effective therapies for these diseases an absolute priority. That is why we have invested 7.2 million euros in research on these aggressive cancers, allowing nearly 1,600 children to access innovative treatments in clinical research.
But if the brain is a vital organ, it is also extremely fragile. The aggressiveness of current treatments still too often leads to severe sequelae that impair the quality of life of young patients. In 2024, the European consortium FIGHT KIDS CANCER, of which we are the initiator, made pediatric brain cancers the priority of its annual call for projects. Following a selection process led by international experts, 8 research projects were selected for their excellence, innovation, and impact on patients, with total funding of 10.7 million euros. Among them, we are proud to support REVIIH-BT, an audiovisual telerehabilitation program aimed at correcting visual deficits caused by brain tumors and treatments, particularly radiotherapy. Telerehabilitation, an innovative strategy, uses new technologies to improve patients’ quality of life.
Restoring Vision in Children and Adolescents Treated for Brain Tumors Through New Technologies
On the occasion of Cancer Awareness Week and Brain Awareness Week, we met with Dr. Michael Reber, a neuroscience researcher (INSERM, University of Strasbourg), and Prof. Natacha Entz-Werlé, a pediatric oncologist (University Hospitals of Strasbourg and president of EN-HOPE SMART4CBT, the PEDIACRIEX of the Northeast region), to learn more about this promising program.
What are the most frequent sequelae in children, adolescents, and young adults with a brain tumor?
Prof. Natacha Entz-Werlé: The most frequent sequelae mainly concern difficulties with concentration and learning. Of course, we also observe significant visual deficits, especially since a certain number of these tumors are gliomas of the optic pathways. Furthermore, a little more than a third of the patients we follow have a tumor in the posterior fossa, which can lead to intracranial hypertension and affect walking, sleep, and balance. Of course, these diseases are complex, and these disorders often combine in the same patient. However, I would say that the most frequent sequelae remain visual impairment, whether it is strabismus, decreased acuity, or an anomaly in the visual field. Precisely, the project we are conducting aims to offer patients visual rehabilitation care developed by Michael and Dr. Éric Bouffet, who initiated this approach in Canada.
Can you describe precisely how visual deficits affect the quality of life of patients?
Prof. Natacha Entz-Werlé: In my clinic, I follow children and adolescents affected by visual disorders, and this greatly complicates their daily lives. Depending on the severity of the visual impairment and the visual field defects, the impact on the quality of life can vary. Nevertheless, almost all of my patients suffer from significant fatigue, which adds to concentration disorders. When we see normally, I think we do not realize how essential vision is in our daily lives, especially for simple gestures like cutting food, reading, or writing. What always impresses me about these young people is their incredible ability to adapt and find ways to compensate to continue living as normally as possible. I support children with severe visual impairment who manage remarkably well by using tools like phones or computers. Some compensate with other senses: I have several patients who have completely lost their sight and who transform their daily lives into a true exploration of touch and hearing. It’s quite fascinating! This clearly shows the importance of visual rehabilitation approaches. Beyond improving visual acuity, they could also strengthen their concentration and reduce their fatigue, which would have a direct impact on their quality of life.
Your project mentions hemianopsia. Can you explain what it is and why you think it could be reversible?
Dr. Michael Reber: Hemianopsia, by definition, is a loss of conscious vision in one hemifield, that is, half of the visual field, on the left or right. This is due to damage to the brain region that processes visual information, located at the back, which we call the primary visual cortex. In patients with brain cancer, this structure no longer functions because it is invaded by tumor cells or because the tumor is located on the path of the connections that transmit information between the eye and this structure. In any case, this region of the brain no longer receives visual information or can no longer analyze it. Thus, children lose what is called conscious vision, which means that either their left visual field or their right visual field disappears. As Natacha pointed out, this poses major problems in daily life, particularly in terms of mobility and independence. Typically, these patients avoid unknown or very dense environments, such as a crowded shopping mall on the weekend.
Hemianopsia is also present in other pathologies, such as after a stroke (CVA). In these cases, it is often transient, which led us to think that it could potentially be reversible. When we published our pilot study with Dr. Éric Bouffet, we included children with stable hemianopsia for at least 18 months. However, we know that after 12 months, spontaneous recovery is very rare without specific care. It was with this in mind that we tested our audiovisual stimulation program, which combines vision and hearing. As Natacha mentioned, when we lose vision, we often compensate with other senses, especially to understand the space around us. Furthermore, researchers have discovered that people with hemianopsia also partially lose the ability to locate a sound in space, particularly in their blind area. This is explained by the fact that, in our brain, some areas simultaneously integrate sound space and visual space to improve perception.
The idea behind our audiovisual stimulation is therefore to combine sound and image to improve spatial perception. I like to give the example of a mosquito in the summer, in the dark. You are lying in your bed, you hear it approaching, moving away, coming back… But it’s impossible to crush it without turning on the light! Our approach is based on this principle: by associating a sound with a moving image, we allow patients to improve their visual performance by performing exercises where they must follow a target more effectively, which emits a sound depending on its position in space.
Example of a test conducted in virtual reality where the child follows a moving target, which emits different sounds depending on its movements.
How did you design such an elaborate test?
Dr. Michael Reber: The concept has existed since the 1980s and was developed by a laboratory in the United States to study spatial attention in humans. It was a test where one had to be able to follow a target among visual distractors, all moving in space. One could follow the target by moving the eyes or by keeping a fixed point in front of oneself while deploying visual attention. At the time, it was purely visual. In the meantime, there has been a lot of work in the 1990s, notably on what is called multisensory integration. We then thought that we should add sound to the target’s movement, and that’s what we recently published. For comparison, rehabilitation systems based solely on visual stimulation take much longer and are much less effective.
I am often asked why this audiovisual device works when we are exposed daily to audiovisual stimulations. The strength of our program lies in repetition. It’s like training: when you repeat a gesture in a sport over and over again, on the day of the competition, your movement will be perfect. However, in daily life, we are indeed exposed to auditory and visual stimulations, but they only last a few milliseconds and repeat randomly. In our program, children follow the audiovisual stimulation for six weeks, every other day, for 15 minutes per session, especially at home. With Éric Bouffet, we made sure that this was compatible with their school and extracurricular life.
Prof. Natacha Entz-Werlé: When Michael and Éric contacted me about this protocol, I must admit I was immediately very interested from a neurodevelopmental perspective. We know that the regular repetition of certain learning is the key to better assimilation. This creates neurological circuits and new connections. It is an excellent way to mitigate the side effects of brain cancers, and I found this approach extremely promising. Especially since the children are doubly stimulated, which further improves their learning abilities. Finally, I am very confident in the concepts of rehabilitation and their ability to mitigate certain sequelae. Other approaches are emerging today, particularly in neurocognition, and they are very promising for limiting the sequelae of children and adolescents affected by cancer, especially when it is located in the brain.
Can you describe the typical journey of a patient who will participate in the study?
Dr. Michael Reber: First, the doctors identify the participants based on a particular criterion: the presence of hemianopsia, if possible stable. There are no other specific criteria related to the child’s treatment, possible surgery, or remission status. We chose not to set exclusion criteria on these points to include the broadest possible representation of patients.
Prof. Natacha Entz-Werlé: Yes, exactly. This is a fairly heterogeneous population, and that is precisely what is interesting. One of the objectives is to be able to apply this protocol on a European scale, in several centers, with different languages and learning methods. I find this exciting because it would allow us to integrate this tool into the care pathway of future patients, provided we demonstrate its effectiveness. For example, this therapy could complement other interventions such as physiotherapy or other care, and thus significantly contribute to improving the quality of life of patients on a daily basis. Of course, we are talking about technologies that have a significant cost. It is therefore essential to design the protocol well in advance to ensure its applicability to a large number of patients in various contexts. We must also ensure that future access will be possible. There is therefore a dual major challenge: clinical and realistic.
You use virtual reality, a technology whose use is recreational. Does this motivate patients even more to participate in the study, and as a result, can we expect even greater benefits?
Dr. Michael Reber: Absolutely. When patients come to their center, a person presents them with the virtual reality headset, and they perform several tests to familiarize themselves with the tool. We take this opportunity to make measurements to evaluate their initial performance, particularly their baseline speed. This data then serves as a reference throughout the eight weeks of exercises, making it almost a form of personalized treatment. Once this step is completed, each patient takes the headset home and uses it every other day. In the laboratory, we adjust the parameters and monitor the patient’s performance in real time. We first observe a learning phase, where speed progresses rapidly, followed by a plateau phase that lasts a few sessions, before a new progression resumes.
At the midpoint, a visual field test is normally performed in the clinic, but we are working to integrate it directly into the headset to avoid travel, especially for patients with vision problems. One of our goals is to make these rehabilitation exercises accessible, particularly in underserved or rural areas. The entire protocol is rigorously controlled, and patient safety is monitored. We have set up a questionnaire to monitor any side effects, such as nausea, dizziness, or headaches. If this occurs, it is enough to stop the session, and everything returns to normal within ten minutes.
It is true that we use products initially dedicated to entertainment, in which we integrate research applications. Some call these Serious Games, which generate strong adherence. Moreover, out of the ten children included in Toronto, none refused to use it.
Your preliminary study shows improvements in vision for patients with brain cancer, but these do not seem to last completely over time after the protocol is stopped. Do you plan to extend the duration beyond 8 weeks?
Dr. Michael Reber: Yes, that is a possibility. We found during the study that 4 weeks were insufficient, which is why we moved to 6 weeks to obtain initial results. For this European program, we decided to go up to 8 weeks, but we also do not want it to become too long, at the risk of tiring the patients and making follow-up more complicated. If adherence decreases, the interest of a long program fades, so we need to find the right balance. The idea we have would be to have an initial phase of 8 to perhaps 10 weeks, with sessions of 15 to 20 minutes every other day, and then, six months later, to reuse the tool for one to two weeks to maintain the benefits. This is a possibility we would like to test in a future study.
Prof. Natacha Entz-Werlé, can you explain how this project fits into the research deployed by your PEDIACRIEX northeast center, EN-HOPE SMART4CBT?
Prof. Natacha Entz-Werlé: Absolutely. Our PEDIACRIEX research center, dedicated to pediatric brain tumors, was labeled, like the others, in November 2023. From the start, we wanted to integrate new teams, with the possibility of opening a third research program. Finally, we chose to deploy two, one of which explores the quality of life through human and social sciences. What we clearly lack are rehabilitation projects with a strong biological component, like Michael’s. Rehabilitation is still a very vast field to explore and put at the service of patients with brain cancer. I am thinking in particular of focusing or neuromediation techniques, which can be carried out at home thanks to adapted software. In any case, it is an area we can develop within our PEDIACRIEX. This would allow us to better understand the sequelae, particularly those related to radiotherapy, and above all to provide adapted solutions.
Why Support Innovation in Pediatric Cancers?
Supporting innovation in pediatric cancers is essential to offer new hope to children, adolescents, and young adults affected by these rare and aggressive diseases. Every year, thousands of children are diagnosed with cancer, but current treatments are often based on protocols developed for adults, leading to severe side effects and insufficient survival rates. Investing in the research and development of innovative therapies—such as immunotherapy, personalized medicine, or nanotechnologies—can improve the chances of recovery while reducing long-term sequelae. By supporting this scientific advancement, we contribute to accelerating the availability of more effective and adapted treatments for young patients. Raising awareness and mobilizing around this cause is therefore a major public health issue, where every action counts to save lives.
Together, let’s continue to accelerate research to conquer childhood cancer! GO, FIGHT, WIN!
Discover how to help Imagine for Margo fight pediatric cancers here.