Panel Discussion: Models to advance science and outcomes for Rare CNS tumors

Panel Discussion: Models to advance science and outcomes for Rare CNS tumors

Panelists and Affiliations

Marta Penas-Prado, Elizabeth B. Claus, Erin M. Dunbar, Mark R. Gilbert, Richard J. Gilbertson, Martin van den Bent, Roel Verhaak, Terri S. Armstrong

Marta Penas-Prado MD, MSc. (Moderator). Associate Research Physician. Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health
Elizabeth B. Claus MD, PhD. Professor of Biostatistics and Neurosurgery, Yale University. Attending Neurosurgeon and Director of Stereotactic Radiosurgery, Department of Neurosurgery, Brigham and Women's Hospital
Erin M. Dunbar MD. Director of Neuro-Oncology. Brain Tumor Center, Piedmont Healthcare
Mark R. Gilbert MD. Chief Neuro-Oncology Branch, Senior Investigator and CCR Deputy Director.  Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health
Richard J. Gilbertson PhD. University of Cambridge. Li Ka Shing Chair of Oncology. Head of Department of Oncology, Cancer Research UK Cambridge Centre
Martin van den Bent MD, PhD. Professor and Head of Neuro-Oncology. Erasmus MC Cancer Institute
Roel Verhaak PhD. Professor and Associate Director of Computational Biology. The Jackson Laboratory
Terri S. Armstrong Ph.D., ANP-BC, FAAN, FAANP. (Moderator). Deputy Chief Neuro-Oncology Branch and Senior Investigator. Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health

Key message

Rare CNS tumors pose many challenges - the first step to address them is to direct the attention of the public, clinicians, researchers and funding agencies. A panel of experts highlighted major real-world challenges, collaborative models that have overcome some of these challenges, and areas in critical need for development.


Brittany Cordeiro, Project Manager, NCI-CONNECT, Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health.

Kristin Odom, Communications Editor, Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health.

Kendall Morgan, Scientific editor.

Panel goals and summary

Surprisingly, although individual rare cancers only affect a very small number of people, collectively they represent about one fourth of all cancers. Particularly, primary central nervous system (CNS) tumors are rare compared to other oncologic diseases. When considering all malignant and non-malignant histologies together, their average annual age-adjusted incidence rate is about 23 per 100,0001. Some primary CNS tumors are extremely rare, representing less than 2% of their total and with annual incidence per histology that varies from only a few cases to about 1,000 per year in the United States2.

This panel discussion closed a virtual course on the challenges of clinical care and research in rare central nervous system (CNS) tumors held on September 25, 2020 and sponsored by the National Cancer Institute’s (NCI), NCI-CONNECT program in partnership with the Society for Neuro-Oncology (SNO). The content of this virtual course has published as a Supplement to Neuro-Oncology. We assembled a panel of neuro-oncology experts and leaders of international projects and organizations contributing to make progress on understanding these tumors and advancing patient care – CERN Foundation (Collaborative Ependymoma Research Network), NCI-CONNECT (National Cancer Institute - Comprehensive Oncology Network Evaluating Rare CNS Tumors), GLASS Consortium (Glioma Longitudinal AnalySiS), International Low Grade Glioma Registry, and EURACAN (European Reference Network for Rare Adult Solid Cancers) (Figure 1). This panel highlighted major challenges of clinical care and research for rare CNS tumors (including those brought up by the ongoing COVID-19 pandemic), collaborative models that have successfully overcome some of these challenges, and areas in critical need for further development.

Some of the real-world challenges in patient care include the lack of evidence, making clinical decisions and insurance coverage difficult, and the limited availability of clinical trials. Furthermore, important barriers to patient participation to trials include geographic dispersion and distance from centers offering such trials. The solutions include a multilayer approach: 1) Establish effective networks of specialized centers working in collaboration with community centers closer to the patient and providing expert guidance, as modeled by NCI-CONNECT and EURACAN; 2) Develop disease-specific guidelines to determine the correct diagnosis in patients with rare cancers, which represents the first and essential step to select the right treatment, estimate prognosis, and identify subpopulations with actionable molecular alterations that may benefit from targeted therapies; 3)  Establish collaborative work between academic centers offering expertise and clinical trials and centers in the community providing standard-of-care tests included in the trial or even administering the experimental treatment in some circumstances; 4) Create and enroll patients to registries collecting comprehensive clinical data and tumor specimens and/or germline samples, which help collect high quality data on patients not participating on therapeutic trials and generate hypothesis for future trials; 5) As shown by the COVID-19 pandemic, there is an unprecedented opportunity to implement telecommunications and increasingly popular and accepted telehealth approaches as a strategy to facilitate these objectives, beyond the pandemic; 6) Finally,  patient advocacy organizations can play a key role as a liaison to connect patients with rare CNS tumors and expert health care professionals.

From the point of view of research in rare CNS tumors, challenges include the small numbers of patients with a given diagnosis, bias and extrapolation from other more common tumors when approaching research questions or elaborating hypotheses, lack of good preclinical models, disintegration and duplication of research efforts due to investigators working in silos, and challenges of international collaboration due to complex regulatory oversight. Moreover, the COVID-19 pandemic brought up the additional challenge of greatly limiting in-person networking, a critical step for the launching of many collaborative projects. Solutions include the need to work in teams, as exemplified by the Glioma Longitudinal AnalySiS (GLASS) consortium, and reduce barriers to patient participation, as modeled by the Low Grade Glioma Registry. CERN (Collaborative Ependymoma Research Network), is an example of breaking silos. The three key elements identified by the panel as critical to advance research are collaboration, trust, and funding.


Panel Discussion

Marta Penas-Prado: I would like to start our discussion putting patients first.  From the real-world perspective, Dr. Dunbar, how do you approach the care of patients with rare CNS tumors? What do you think are the biggest hurdles on providing this care?

Erin Dunbar: Some of the major hurdles include patient heterogeneity and a lack of practical wisdom and clinical mentors for community providers like me. Even if we develop a plan that we feel comfortable offering to a patient, many times there is no published, evidence-based guideline to support these decisions.

The absence of guidelines also impacts insurance coverage. In the U.S., for example, the National Comprehensive Cancer Network (NCCN) guidelines have created a mechanism recognized by the Centers for Medicare and Medicaid Services (CMS) as a mandated reference for establishment of coverage policy and coverage decisions for cancer treatments. If treatment is not covered by insurance or if there is no known standard approach to a rare tumor treatment, then we look for clinical trials and registries. However, there's a paucity of clinical trials and registries for patients with rare CNS tumors. There is a need for a unique and individualized clinical pathway for every one of these patients who are invariably feeling very alone. To overcome that, we need to connect with worldwide experts to find support. However, there’s a lack of systematic education, support, and resources, not only for our patients with rare cancers and their caregivers, but also for us as physicians. I recognize and accept that I need to connect myself to a multidisciplinary team and experts outside my institution. The National Cancer Institute (NCI) and other professional organizations worldwide are my lifeline.

Marta Penas-Prado: Dr. van den Bent, can you add to that?

 “Every right treatment starts with the right diagnosis.” – Dr. van den Bent

Martin van den Bent: First, it’s a good idea to optimize the diagnostic process because every right treatment starts with the right diagnosis. These are rare diseases, and, thanks to novel discoveries, they are being subclassified even further into less common subtypes. It becomes critical to identify those patients with rare cancers and to make sure they get the right treatment in the right centers. However, doing this often requires centralization, and centralization can be difficult. Patients have to travel. Doctors have to be willing to understand their own limitations and refer patients to Centers of Excellence3.  If we want to make any progress in these rare diseases, we have to work to establish networks, including a hub and the spokes, which are our peer referral centers that can organize the diagnostic process and get patients the needed treatments recommendations.

In the U.S., you’re fortunate to have NCI-CONNECT and funding from the Moonshot Program. In Europe, we have a European network (EURACAN) where the European Union tried to do the same, but by way of teleconsultation4. However, there are many countries in Europe, each with its own health care system and many hospitals, which is challenging. You need to have a network with people collaborating closely and knowing when to refer a patient. You need algorithms that guide you in what to do and how to run the diagnostics. Based on the diagnosis, you then need to identify the best treatment you can offer. Unfortunately, it’s a very complex and often lonely process for the patient.

Marta Penas-Prado: Dr. Claus, can you please share your perspective as a physician working in an academic and referral center?

“Working together is the key.” – Dr. Claus

Elizabeth Claus: I echo what others have already said. There’s a critical need to collaborate. We certainly see the confusion that patients have not knowing where to turn or what the best course of action is. One thing I'd like to reinforce is that—even if you are in a region that doesn't have a large academic center or a tertiary cancer center—in most of these larger cancer centers, the staff are willing to work with local physicians to help patients get the care they need. Patient organizations such as those in the NCI-CONNECT Rare Brain & Spinal Tumor Network also are invaluable to help get information to patients and to send them to us if we can help. Working together is the key.

Marta Penas-Prado: Let’s shift gears and talk about research. What is the biggest challenge in advancing research for rare CNS tumors?

Richard Gilbertson: One of the biggest challenges to studying any rare disease are our preconceptions when we extrapolate from observations in other diseases. I'll give the example of choroid plexus carcinoma, a very rare brain tumor that my lab is working on5. It's impossible to do clinical trials in this disease because of the very low number of cases (for example, there are only about two cases a year in the UK that would be eligible for a clinical trial, and just five patients each year in Canada). If you analyze the research enterprises being leveraged against choroid plexus carcinoma, a lot of it has come from the bias of glioblastoma, a completely different disease, or even from other epithelial cancers. It's only by taking a completely different approach to choroid plexus carcinoma that we're starting to understand how we might make inroads to treat it.

Marta Penas-Prado: Dr. Verhaak, what is the most important factor to help advance research for rare CNS tumors?

Roel Verhaak: First, it's critical to work in teams. One very practical reason is, if you want to study specimens from patients with these diseases, the only way to collect a meaningful number of such specimens is through a worldwide or at least a nation-wide collaboration, as we successfully did in the Glioma Longitudinal AnalySiS (GLASS) Consortium6. In the past five years we built this Consortium with the goal of generating molecular data from multiple time points from a set of patients with glioma. The aim is to understand what changes occur over time in this disease and how these tumors become progressively treatment resistant. Last year, we published the analyses of the first 250 patients, which is the 14 percent of our final goal of including 1,500 patients7.

We can’t account for all the heterogeneity of this disease, but we can account for a substantial portion of it. Hopefully, that will allow us to compare, for example, patients who've undergone both chemotherapy and radiation therapy to those that only have undergone radiation or only chemotherapy or no therapy at all, which is not uncommon for patients with oligodendroglioma. We continue to make progress in meeting these goals. In doing so, we're continuing to strengthen the network of more than a hundred investigators that are part of the GLASS Consortium today.

“Having access to better model systems would greatly enhance our research of these diseases.”– Dr. Verhaak

Another issue complicating advances in rare CNS cancer research is the lack of good preclinical model systems. An example are low-grade gliomas, which is one disease that we are interested in. Developing better models is critical, even though many have tried with limited success so far. It's certainly a very complex problem but developing and having access to better model systems would greatly enhance our research of these diseases.

Marta Penas-Prado: Dr. Claus, do you have any additional thoughts?

Elizabeth Claus: One of the biggest issues is the low number of patients participating in research. One way to increase numbers is to reduce some of the barriers and especially social barriers to access research8. To overcome those barriers, patients need to have trust in what we’re doing. They need to understand the ethics and the privacy. We should do a better job at getting these concepts across to build trust and encourage participation.

Marta Penas-Prado: Another important stumbling block to research progress is that we are all too often working in silos. How do we break these silos?

Martin van den Bent: It’s important to recognize that those silos are the result of the way our health care systems are organized. In some ways, this organization helps us to work; in other ways, it poses impediments. It also brings resistance to change. What helps to break these silos are funded programs like NCI-CONNECT, which can start building networks and working collaboratively on research and care. If there is no funding—no support—it becomes very difficult to develop even the tiniest initiative.

Another challenge is that it has become tremendously difficult to collaborate between Europe and the United States due to regulatory and legal issues. If we want to do a trial in Europe and collaborate with colleagues in the U.S., and, for example, the trial includes radiation therapy, we have to adhere to quality control and privacy regulations in the U.S. as well as those in Europe. This makes global collaborations extremely difficult, slow, and costly. Of course, there is a need for well-designed clinical trials with good regulatory oversight and protection of patients. But in rare diseases, those protective measures for the patient can be counterproductive and result in an inability to collaborate on a global scale.

Mark Gilbert: Dr. van den Bent is correct. There are still regulatory challenges that make international collaborative research difficult. But at the end of the day, we're all in this together. There are patients with these rare cancers all over the world. The opportunity to do international collaborations is key to making progress. If you consider a disease in which a single country will have fewer than ten patients diagnosed per year, it’s incredibly difficult to conduct clinical trials if we work in isolation, even when testing really refined treatments. We also need our industry partners in biotech and pharma to work with us as well.

“It is not only possible to break silos, it is necessary.”– Dr. Gilbert

The CERN Foundation (Collaborative Ependymoma Research Network), demonstrated how effective collaboration can be. CERN integrates laboratory-based basic research, clinical trials and patient outcomes research successfully and it has become a very cohesive unit over time. It's a model that works and a paradigm of how adult and pediatric researchers and physicians can collaborate in the space of these rare diseases. Understanding the age-related differences or similarities and utilizing all those resources to better understand these tumors is what we need to do to make any inroads. It is not only possible to break down silos, it's necessary.

Richard Gilbertson: We are in a system that's intrinsically competitive to get funding, to publish, and to advance your own career. I’m a pediatric oncologist, and we’ve had to work together because of the rarity of the diseases we study. From what I’ve observed, the single biggest accelerant to progress in pediatric oncology has been trust, without a question. It's not been money; it's been trust between individuals.

“The single most important ingredient in this success has been trust among researchers and a willingness to share.” – Dr. Gilbertson

Several years ago, we started a meeting called Medulloblastoma in the Mountains. The idea was that all of those who were leading research laboratories and clinical trials on medulloblastoma would get together once a year. The only requirement was to share unpublished data. Work derived from these workshops has resulted in high-profile papers, and it has been instrumental to establish the updated classification for medulloblastoma in the latest revised edition of the WHO Classification of CNS tumors9. The single most important ingredient in this success has been trust amongst researchers and a willingness to share.

Roel Verhaak: As a researcher primarily focused on adult brain tumors, I’m quite jealous of how the pediatric neuro-oncology community has been able to self-organize and be so extremely successful. Nevertheless, some of these initiatives exist in the adult brain tumor world, too, with The Cancer Genome Atlas (TCGA) as a prime example. The GLASS Consortium counts towards that as well. Better collaboration is clearly the way forward.

Erin Dunbar: I'd like to add another opportunity to break silos that involves clinical trial design. Some incredibly archaic trial requirements still mandate, for example, that chest x-rays and routine blood draws must be done only at the institution of the principal investigator. In some instances, local providers are not allowed to perform even the most routine care included in the trial. Additionally, some trials list very restrictive inclusion criteria that would not be generalizable to the success of the treatment in the greater population. I hope the next generation of clinical trials

“I hope the next generation of clinical trials will be more pragmatic and allow more routine care to be done in local communities.”– Dr. Dunbar

will be more pragmatic and allow more routine care to be done in local communities. Whereas the FDA issued specific guidance on conduct of clinical trials during the COVID-19 pandemic to facilitate local care when feasible, these recommendations are not binding and it remains to be determined if any of them will still apply once the risks of the pandemic subside ( Finally, I want to note that, despite all efforts to design and implement clinical trials for patients with rare CNS tumors, clinical trial options are still sparse and there will remain a population of patients looking for non-trial access to medications without regulatory approval for their disease. In the U.S., the Right to Try Act or the expanded access designation are potential but often difficult to implement pathways for patients to receive an investigational medical product outside of clinical trials when no comparable or satisfactory standard therapy options are available and participation in trials is not possible. Another goal I would propose is encouraging patients that are taking medications off-label to enter registries that are both obligated and interested in collecting as much data as possible.

Terri S. Armstrong: How has the COVID-19 pandemic impacted research in rare cancers and in rare CNS tumors, in particular?

Roel Verhaak: My own laboratory is about 75 percent computational and 25 percent in the wet lab. My wet lab trainees and colleagues had a small pause, but after about four weeks, they were able to get back into the lab. My dry lab trainees and colleagues never really paused at all. I'm quite happy and proud of how we've been able to move forward, despite the challenges, and in a way, it's brought us closer together.

Richard Gilbertson: Beyond the experience of any one lab, I have many concerns about how the pandemic is affecting the economy, the workforce, and the mental health of many individuals. In the United Kingdom, we are at risk of losing a generation of researchers if we're not careful. There are two main reasons for that. First, losing a year of work can have a devastating effect on an individual working on their PhD, with an impact on how they view their future and their research plans. Every single person who's doing a PhD in the UK involving wet lab research will lose at least a year. There's a real question over who will pay the stipends of those individuals for the next year.

Second, in the UK, Cancer Research UK raises about £600 million a year, but it’s currently down about £160 million in its funding. That will have a major impact. This loss of funding probably isn’t going to hit breast cancer, prostate cancer, or lung cancer, but it may well hit rare cancers. We don’t need to wring our hands in fear, but I think we do need to be really cognizant of the challenges ahead.

Terri Armstrong: Dr. Gilbert, do you have anything to add to that, from the NCI perspective?

Mark Gilbert: The NCI and the NIH itself has been greatly impacted. It's only been since the end of the summer of 2020 that people who are not directly involved in patient care were allowed back onto campus. Our trainees and our junior faculty are feeling the strain. The NIH is a very large training organization. Many people come here for a finite amount of time. Visas have limitations. We have many international trainees, and to date, the ability to extend visas has not matched our interest in allowing these trainees to extend their time with us. We must recognize not only that people are feeling stressed, but they do have a career goal. We don't want to lose the best and the brightest because they get discouraged and can't do their work.

On the other hand, we also don't want to put people in harm's way. I predict that the individuals who will ultimately have a great chance of success are those who are taking advantage of this difficult period and lull in certain kinds of activities to learn new techniques. There's evidence that many people are doing just that. For example, there has been oversubscription at the NIH in bioinformatics courses. So, more people will be self-reliant on doing the more straightforward analysis of genomic data. But there will be negative consequences, and as leaders and mentors, we need to recognize individual struggles and be as flexible as possible with our junior colleagues.

Terri Armstrong: In terms of how we provide care and how we conduct trials, what has the impact of the pandemic been and what are the implications for patients with rare CNS tumors?

Mark Gilbert: On one side, we are increasing the use of virtual platforms for patient care. In the rare disease space, we are looking to a very broad geographic area to accrue patients. Virtual platforms are useful to screen patients and discuss the trial, including eligibility, requirements, potential side effects—all things we’ve typically done in person—prior to the patient traveling anywhere. In this way, the likelihood that they’re both eligible and interested increases before they need to travel a long distance.

On the other hand, though, it's very difficult for patients to travel great distances to find specialized care or to participate in clinical trials in the context of the pandemic. We must find ways to relax some of the requirements. As Dr. Dunbar pointed out, we should be able to have many of the tests and evaluations done locally where the patient lives. In certain instances, even treatments could be administered remotely in established centers that have the appropriate credentials. We need to make experimental treatments available closer to the patients and allow their local teams to do some of the work, so it remains logistically viable for patients to participate in trials.

Terri Armstrong: Dr. van den Bent, do you have anything to add, from your perspective in Europe?

Martin van den Bent: Yes. I'm working in a small country, which means that borders are another impediment to patient care and clinical trial participation. Much of the work we are doing to circumvent that is to work in a retrospective manner. We are enrolling many patients to a large basket project in the Netherlands, which allows treatment with various agents regardless of the tumor histology10. We are developing databases to collect data from individual patients.

There’s been a silver lining in that we have learned to work from a distance with telecommunications. But we are missing those more casual interactions and conversations that you’d normally have with your colleagues after an in-person meeting and help initiate collaborations. We’re missing the intangible value of networking that's very important for the development of new projects and new relationships. Our young colleagues are not being raised in these networks. That's the thing that we must be aware of and must deal with urgently.

Elizabeth Claus: In some ways the pandemic has improved our ability to contact people and have them feel comfortable with online networking or social media. While I think there are many silver linings, it is challenging to reach patients who don't have the ability to use these online tools.

Erin Dunbar: When it comes to telehealth in research, we will have to demonstrate that telehealth is not inferior, or that it is in many cases even superior to traditional in person interactions in terms of fostering diversity, inclusion, equality, or other endpoints.

Marta Penas-Prado: Dr. Claus, how important is the diversity of the population to your work, and what is your advice for engaging these diverse populations?

Elizabeth Claus: Diversity is very important. For our work, we define diversity very broadly, in terms of ethnicity, race, gender, sex, but also characteristics like socioeconomic status (SES) and whether a person resides in an urban versus a rural setting. In keeping with many epidemiological studies, one of the things we've noted in the Low-Grade Glioma Registry is that more individuals of high-SES, primarily White/Caucasian ethnicity, are typically treated at large academic centers, and are more likely to live in an urban setting. But the data also show that most low-grade glioma patients are treated outside of such centers. We want to make sure that we include those people in registries, and not just for genetic reasons. We know that risk and response to treatment as well as outcomes can vary by factors like race and ethnicity and sex. But it can also vary based on these other factors as well.

We've been trying to achieve this goal by engaging patient organizations. We have a couple of great patient researchers that we work with. We’re learning from them what it means to be an equal partner by letting them be, for example, a co-PI on a grant or a co-author on a paper. If you have funds, you can consider paying them for their time or otherwise recognizing the efforts that they make.

We’re also working to remove some barriers by making participation easier for patients.  For example, we ask patients in the registry to send us a pathology report so we can confirm the diagnosis. However, this can be difficult and it’s the number one reason why people have started to join the registry and then not completed it. We hope to overcome these challenges using an electronic health record platform that lets us, with patient permission, go into electronic health records. We can make updates and follow patients without having to bother them. We can merge records across different systems. Efforts like this are making a difference and then, in the end, the key is collaborating with other researchers.

Marta Penas-Prado: Dr. Gilbertson, you’ve made seminal discoveries in several rare cancers, what do you think is necessary to continue accelerating our understanding of all rare CNS tumors?

Richard Gilbertson: I think the critical step is to keep an open mind. What my lab is particularly interested in currently is the role of aging in cancer. We've had an interest in the cell of origin of pediatric brain tumors. We’ve mapped where these tumors come from, and we’ve been able to identify some of the genetic events which transform those cells. In that process, we realized that we needed to take a much broader approach in the organism. It might be a strange answer to your question, but I believe that we will understand the most about the brain if we look at the entire organism in development. So, what we're doing now is studying the cells of origin for cancers across about 12 organs throughout development.

We've just built a universe of stem-like cells in all tissues including 12 tissues from embryogenesis all the way through to adulthood, and that's unmasking quite remarkable insights. For example, as a pediatric oncologist, I've always wondered why children don't get more cancer. It's incredibly rare in kids, and yet kids are growing more rapidly, and their cells are dividing more rapidly at any point of development. We've known for many years that evolution must have developed a process that protects pediatric or developing tissues from cancer. There must be mechanisms to protect those tissues at this critical phase in development when they're most prone to malignancy. What we've realized by taking a holistic view of the cells across all tissues is that developing tissues have these intrinsic mechanisms which protect against cancer—which stop those cells being transformed. The reason we're interested in that is because most of them probably are epigenetic. These are plastic mechanisms in cells, and if we could reactivate those in adults, then we might have a fantastic way of protecting adult cells from becoming cancer.

The dogma in cancer has been that an individual needs to get old enough to recruit enough mutations to develop cancer. But, the other part of the story is that adult cells don't need to protect themselves from malignancy like juvenile cells do because they don't have a lifetime to live. It's that sort of open-mindedness and approach to tissue development in cancer, which I think will impact the next generation of discoveries.

Marta Penas-Prado: Dr. van den Bent, what should be the driving question as we go forward in rare CNS cancer research?

Martin van den Bent: The driving question will always be improving outcomes. What worries me now the most is that we have several agents that work in very small subpopulations, but we are not able to identify these patients with readily available platforms. We need to develop a reliable way to identify those patients. From the whole group of patients with CNS tumors, we need to implement a testing strategy that will identify those patients that should undergo further scrutinizing for those rare diagnoses, and then we can offer them a treatment.

Marta Penas-Prado: Dr. Gilbert, your leadership in CERN and the NCI-CONNECT program has been an example of transdisciplinary research and approaches for advancing the science and care of patients with rare CNS tumors. How do you see the role of the NCI and the Intramural Program in continuing this work? Can you speak to the inclusion of advocacy organizations in NCI-CONNECT and the importance of their role?

Mark Gilbert: One of my motivations to move to the NCI was the opportunity to work in an environment where it is possible to be a galvanizing force, to bring together people in a variety of programs and projects, both nationally and internationally. The NCI-CONNECT is a perfect example where the funding has led to a whole series of initiatives. We must recognize that rare diseases individually affect a very small subpopulation, but collectively it's been estimated that 25 percent of all cancer would fall into the designation of rare cancer11,12,13. Obviously, there are many different cancer types included in that 25 percent.

From a scientific standpoint, rare cancers have led to seminal discoveries, such as the BCR-ABL1 fusion oncogene in chronic myeloid leukemia and chromothripsis14. That was one of the first examples of chromosome shattering leading to cancer. Another example is retinoblastoma (RB1) as a tumor suppressor gene—as an indication of the genetic association in oncogenesis.

Rare cancers have clearly contributed to our understanding of cancer in general. They are also a serious unmet need. The NCI and the NCI-CONNECT provide an unprecedented opportunity to reach out and to achieve global impact. We have resources that enable us to carry out special endeavors such as collaborating with many colleagues around the world, studying patient outcomes and developing clinical trials for these rare tumors and we've been very fortunate to establish many collaborations.

“Patient advocates are getting the word out to patients with these rare conditions who are scared and alone.”
– Dr. Gilbert

When it comes to studying rare diseases, patient accrual to research studies is critical and to get patients involved, they need to know about the program. That's where patient advocacy has been instrumental. I can't thank our advocacy partners to the NCI-CONNECT enough. Patient advocates are getting the word out to patients with these rare conditions who are scared and alone. Many of those patients end up being referred to us. Then, through the network we have built, including 33 centers around the country that make up the NCI Neuro-Oncology Branch's Brain Tumor Trials Collaborative, we can provide them with expert care closer to home. All those factors together have contributed to the success of the program, in addition to educational opportunities like this today.