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Dr. Sabine Mueller - Increasing the number of early-stage neuro-oncology clinical trials

Dr. Sabine Mueller started at the Máxima center earlier this year as a consulting scientist. She is specialist in pediatric neuro-oncology and aims to implement more early-stage clinical trials that will give children with brain tumors access to new forms of treatment. She also works at the University of California San Francisco (UCSF) and is co-project leader of PNOC, the Pacific Pediatric Neuro-Oncology Consortium, a group of 37 research hospitals that the Máxima center also joined since end of 2021. Mueller recently visited the Máxima center and we asked her some questions.

Pediatric neurology is the common thread in your impressive career. What brought you to this choice and how did your passion for pediatric neurology and more specifically neuro-oncology arise?

Already during my medical training I was fascinated by the human brain and its complexity. During my medical training this interest persisted and after completing a fellow ship in child neurology, I started to specialize in pediatric neuro-oncology. Currently my main focus and passion is on translational science with a focus on developing and conducting  early-stage clinical trials with the goal to develop new treatment methods and a better chance of curing children with a brain tumor.

There are obviously challenges and as pediatric neuro-oncologist you experience a lot of loss and sadness, but we have also seen tremendous progress in some of the tumors we treat that gives me a lot of hope for the future. In addition of having the privilege working with our families and patients,  I also work with a great international group of people to contribute to the cure of these challenging tumors.

What are, from your perspective, the biggest challenges in the field of pediatric neuro-oncology?

If you compare the field of neuro-oncology with other childhood cancers like leukemias, you can see that progress has not been made to the same extent in recent years. For some forms we are achieving nice results, but there is still a lot to achieve. One of the biggest reasons for this backlog in brain tumors is that there are very many different types of brain tumors. Fortunately, since the last five to 10 years we have begun to understand the biology better and we are finding similarities and starting points for treatments. But still, the tumors are in a very complex organ, the brain. And in some cases, the tumor is intertwined with different areas of the brain, making it extra complex and often impossible to remove surgically. Drug treatment is also complicated by the blood-brain barrier that makes it extremely difficult for us to get sufficient amount of drugs to the tumor. There are several studies and clinical trials underway to find a solution to this. For example, we are trying to bypass this barrier via placing a catheter directly into the brain tumor to deliver the therapeutic agent directly. I also see great opportunities in the research being conducted at the Máxima hospital, for example with the direct administration of medication administered using small catheters and the robotic arm, and ultrasound to temporarily break through the blood-brain barrier.

What attracted you to the Princess Máxima Center and what are your future plans and activities at the Máxima? What role do you see for internal and external collaborations?

'Many brain tumors are rare because of their great diversity, or heterogeneity. Because all children with a brain tumor from the Netherlands come together in the Máxima, there is a relatively large research group. Thanks to this large group and the many specialists at one location, we can more quickly reach breakthroughs that will benefit children all over the world.

My goal at Máxima is to implement early phase clinical trials for children with brain tumors  so that children have access to new forms of treatment. One of the first clinical trials we aim to implement shortly is participating in DMG-ACT. In this trial, we are focusing on a very aggressive and currently poorly treatable form of brain cancer: diffuse midline glioma. In it, pre-clinical and clinical researchers work together to bring new therapies and combinations from the lab to the bedside as quickly as possible. At the same time, we want to investigate efficacy in different research models, such as mouse and zebrafish models. We hope to start this study soon at the Máxima together with Dr. Dannis van Vuurden and Dr. Jasper van der Lugt.

To conclude, as a specialist in your field, what do you think the future of neuro-oncology holds?

'I see that the future lies in open international collaborations. As we are learning more and more about the different subtypes of brain tumors, collaborations are needed to assure timely accrual into clinical trials. I also strongly believe that data collected as part of these trials and  that can be shared safely, should be made available to the research community at large in real time. There are still important challenges ahead of us that we need to take on in order to cure more children with brain tumors but maintain a good quality of life, but thanks in part to international collaborations like we have with the Máxima and PNOC, I'm convinced that we can take serious steps forward in the near future.