Children's Brain Tumor Network
As the Children’s Brain Tumor Network has grown, so too have the depth and breadth of its partnerships across institutions, consortia, industry, and philanthropy. This is due in no small part to the creativity and dedication of our CBTN members, who generously devote their time and effort to the realization of our vision – a world where every child suffering from a brain or spinal cord tumor, living anywhere on earth, has access to life saving and life improving therapies best suited for them.
In recent years, CBTN’s leaders across our Foundation Executive Council, Scientific Committee, and Executive Board have embodied that vision, and have used their collective talents and expertise to forge global collaborations, establish disease-specific clinical trial working groups, and so much more.
In the fall of 2022, it was announced that Dr. Sabine Mueller, a CBTN investigator since 2012 and co-lead of the Pacific Pediatric Neuro-Oncology Consortium (PNOC), will be expanding her involvement in CBTN’s leadership by stepping into the role of Executive Board Co-Chair, following the conclusion of Dr. Angela Waander’s tenure in this position. Dr. Mueller brings a wealth of national and international experience in marshalling the collective efforts of diverse teams of research experts toward the establishment of innovative new collaboration frameworks on behalf of children with brain and spinal cord tumors. We’re so excited to have her leadership in advancing CBTN’s mission in this new role.
Sabine Mueller, MD, PhD, MAS, is a pediatric neuro-oncologist caring for children with brain tumors and related genetic syndromes. In her research, Mueller studies treatments for children with brain tumors, looking especially at improving long-term cognitive outcomes. She is a practicing clinician at the University of California, San Francisco (UCSF), is head of the Clinical Program at the DMG/DIPG Center at the Children’s Hospital of Zurich in Switzerland, leads multiple clinical trial efforts, and is co-lead of the Pacific Pediatric Neuro-Oncology Consortium (PNOC)
We recently spoke with Dr. Mueller about her role as the new Executive Board Co-Chair, including her focus on expanding collaborations across the globe and making CBTN data more readily accessible to researchers everywhere.
Q: What made you decide to submit yourself for consideration as the new Executive Co-Chair of the CBTN?
The key driver was that I so strongly believe in the CBTN vision and mission. I'm a strong supporter of generating and bringing together data from a tissue, imaging, and phenotypic data perspective to entice more investigators to work on pediatric brain tumors. Supporting better outcomes for pediatric brain tumor patients remains such an unmet clinical need. I think the original vision of CBTN’s founders, to build this infrastructure so that others can easily have access to resources to inform their research, is incredibly valuable.
I'm really hopeful that this attracts not only more partners in the pediatric neuro-oncology space, but also others who might not have otherwise considered working in this area by making datasets readily available to test new hypotheses, new algorithms, or other technologies.
Q: You’re an incredibly busy researcher, across your clinical practice at the University of California, San Francisco (UCSF), your lead role at the DMG center at the Children’s Hospital of Zurich in Switzerland, leading clinical trials, and acting in a leadership capacity for the Pacific Pediatric Neuro-Oncology Consortium (PNOC). How do you see your role as CBTN Co-Chair augmenting these other efforts?
It's just so nicely synergistic. One of our main focus areas within PNOC is to provide broad access to innovative therapies, and not just within the U.S. and Europe. We are trying to think about this in a larger international context, and within that there's a lot of cross fertilization that can happen within CBTN. In partnership with CBTN, there are so many opportunities to cross intersect in clinical trial development as already have seen as a result of our PNOC/CBTN disease specific working groups.
Within a leadership role at CBTN, I envision driving more integration within the CBTN to empower and share clinical trial data, and not just from PNOC. I’m confident that similar integrations can occur more globally.
Q: You have extensive experience with establishing numerous international research consortia for the advancement of translational research in pediatric neuro-oncology. How will this experience inform any new efforts to expand CBTN’s consortia partnerships, both nationally and internationally?
Overall, pediatric neuro-oncology research remains fragmented, and data collected internationally as part of different efforts are not being harnessed to the fullest extent possible. It can be inherently difficult to share new data, especially new forms of data, out with a much broader community of researchers – considering, for example, the wealth of imaging and clinical outcome data that is being generated currently through clinical trial consortia such as the Children’s Oncology Group (COG), the Pediatric Brain Tumor Consortium (PBTC), the European initiatives, and also our industry partners, to name a few; but having real time access to these data in a meaningful way remains an ongoing hurdle.
Fortunately, the workflows that have been developed within CBTN and PNOC as one example can inform so many other partnerships like COG, or CONNECT, or PBTC. And, conversely, the work of those groups can also assist us, as they’ve encountered similar challenges within the clinical trial context as we do in CBTN and PNOC.
And obviously, we’ll also want to take these lessons learned and apply them to a more global context. ITCC, a large-scale clinical trial consortium in Europe, also encounters very similar challenges. So, my goal is to find opportunities where we can all work together to overcome similar hurdles and open new avenues for progress.
The advantage of clinical trial data is that they are very rich and detailed. However, one key limitation is that we’re only capturing information on one portion of a patient’s overall treatment journey. The power of CBTN is that it provides a framework for incorporating all the molecular, imaging, and other forms of data, which have been collected longitudinally, to provide a more holistic view of a child’s treatment progress over the entire course of their illness, rather than just during the time of a clinical trial, which empowers investigation that cannot be completed otherwise.
So, within that context, I see a great deal of opportunity to harness clinical trial data or other registry data in a more robust way, and to pair that with longitudinal follow-up data that can be collected and empowered through the CBTN infrastructure to inform translational research, basic science research, genomics research, and more.
Another big part of our overall success with establishing new partnerships necessarily has to do with building a great deal of trust. It’s important to remember that, for the individual researcher, so many years of hard work are involved in collecting either prospective cohort datasets or clinical trial data sets. And while we can all agree that, of course, it’s wonderful that CBTN can help harmonize and empower data for the benefit of the whole research community, we need to build in assurances that the contributions of the individual researcher who shares that data will be fully acknowledged so they get the credit they deserve.
Q: CBTN is at a critical growth point, with teams working to process and share new data through our Project Accelerate, clinical trials development across the PNOC/CBTN working groups, and numerous other strategic partnerships in development. What new growth areas are you particularly excited about, and how to you hope to support these efforts in your role as Co-Chair?
I’m particularly excited about the ongoing work of the PNOC and CBTN working groups, which has really expanded opportunities for incorporating CBTN data in the development and further refinement of clinical trials, making valuable data more accessible and easier to utilize.
However, there is still so much more work to be done in cleaning and harmonizing all the new data that are being collected. The challenge now is to be able to deliver these new data to researchers as swiftly as possible once a request has been submitted and in a meaningful way so that researchers can use the data to their full potential.
While working on some of these data ingest and harmonization processes, I’m also really interested in developing options for tiered data access levels to reconcile data requests more quickly and to generate different data packages. This could involve having something like a platinum level which includes everything there is to know about a particular patient, down through gold, silver, or bronze levels, where there is still a great deal of data related to a patient, but maybe not as in-depth as that top level. Depending on the types of scientific questions a researcher may be interested in solving, the depth of their data needs will be different and CBTN should adjust accordingly.
Related to that, it could be beneficial to create pre-built data sets for specific tumor sub-types that can meet a wider variety of research needs and be ready and available for clinicians, data scientists, industry partners or others as soon as they’re needed.
In considering industry partnerships, we often hear about this big buzzword, “synthetic controls” – basically, a type of external research control group generated by using comparative patient-level data – and how beneficial they can be for the development of new therapeutics. CBTN is obviously well-positioned to develop these types of resource, but we need to ensure we can generate them in a timely manner while also ensuring excellence in the data utilized. This is a big next step which CBTN needs to take.
Q: What other goals have you set for yourself and CBTN as you step into this role?
Over the next few years, I would love to see an expansion in collaboration within the international pediatric brain tumor research community, to entice more large-scale research efforts harnessing a global collection of data and working together to amass larger datasets for even some of the rarest of tumor types.
I’m also excited to support CBTN on its current trajectory of incorporating phenotypic and other forms of multi-omic data through these important partnerships we’ve established with the NIH and other entities. Efforts in this area have thus far been fantastic.
But beyond incorporating and harmonizing newer omics-based data with what’s currently available through the Pediatric Brain Tumor Atlas (PBTA), It will be important to incorporate new forms of clinical and imaging data, as we focus more on functional outcomes, like cognitive and quality-of-life outcomes and so forth. The work that’s been done in these areas recently has shown a great deal of promise.
Further, there is a great deal of potential for CBTN to build and strengthen partnerships with other trial consortia and other cohort studies. We’re already collecting so much valuable data, but a subsequent challenge will be to improve our ability to streamline processes of integrating these other databases with what’s available through CBTN, and to make these valuable data more readily available for researchers.
CBTN’s Scientific Director, Adam Resnick and the CBTN data team have already started to develop frameworks for directly extracting data from patient electronic health records (EHR), to cut down on the amount of time needed for manually entering these data. But this will continue to be a major priority area in the immediate future, so that we can empower data and put them into the hands of researchers as quickly as possible.