The Chordoma Foundation

Organizational Profile

The origin of the Chordoma Foundation dates to 2006 when a small group of chordoma survivors and family members motivated to improve the plight of those affected by chordoma connected through an online support group. Soon thereafter, several members of that group met at the annual conference of the National Organization for Rare Disorders. There, this group resolved to work together to create an organization dedicated to advancing the interests of chordoma patients everywhere. In February 2007, members of this group formed the Chordoma Foundation as a vehicle to organize and strategically channel the collective resources and efforts of everyone who desires a better future for those affected by chordoma.

The Chordoma Foundation is a 501(c)3 tax exempt organization incorporated in North Carolina. Though founded and headquartered in the United States, the Foundation’s mission and reach are global; it exists to serve the worldwide chordoma patient community and partners with healthcare providers, scientists, and companies around the world to advance research and improve patient care. CF views as its constituents not just chordoma patients, but everyone whose life is touched by chordoma, including family members, caregivers, and healthcare providers.

CF is governed by a Board of Directors comprising members of the chordoma patient community, as well as experts in relevant fields including law, finance, management, and medicine. Day-to-day operations and programmatic activities of CF are carried out by a professional staff with support from a host of volunteers across the globe. The staff and Board are counseled by three advisory boards—Medical, Scientific, and Community. The Medical Advisory Board (MAB) is comprised of leading physicians representing each of the primary specialties involved in caring for chordoma patients. The Scientific Advisory Board (SAB) includes leaders in chordoma research as well as other scientists with deep expertise in relevant areas such as cancer genomics and drug discovery. The Community Advisory Board (CAB) is composed of patients, caregivers, and family members across the world who represent the needs and perspectives of the chordoma community.

Funding for the Foundation’s work comes primarily from individuals within the chordoma patient community and those who care for them, with additional support from philanthropists and foundations that see the Foundation’s work as a model for what can be done to strategically address the challenges posed by a rare cancer. Other sources of funding for specific projects include governments and pharmaceutical companies.

Goals

CF relentlessly pursues three core goals to improve the lives of those affected by chordoma: better treatments, better medical care, and better patient experience .

Better Treatments

Existing treatment options for chordoma are inadequate and better treatments are urgently needed—treatments that enable patients to survive longer with better quality of life. Though advances in surgery and radiotherapy enable some patients to be cured, even with state-of-the-art care, more than half of chordoma patients ultimately experience disease progression. In addition to providing insufficient disease control, currently available treatments too often leave patients with deficits or complications that can significantly reduce quality of life. Moreover, when patients relapse after primary treatment, long-term survival is low and disease control is rarely, if ever, achieved. Unfortunately, therapies that can cure or effectively control metastatic or locally advanced disease do not yet exist. As a result, the median duration of overall survival in the Unites States remains 7.7 years, a figure CF is determined to change.

To improve these odds, CF seeks to catalyze the discovery and development of new treatments that benefit chordoma patients at every stage of the disease and will, ultimately, enable all patients to be cured. That means finding treatments that reduce morbidity and the risk of progression in the primary setting, as well as treatments that can effectively control advanced or metastatic disease. It also includes treatments that are effective for patients with tumors of every anatomical location: skull base, mobile spine, and sacrum.

Better Medical Care

CF believes that lives can be saved and outcomes can be improved by optimizing the care provided to chordoma patients. With state-of-the-art care, in certain circumstances, high rates of disease control and overall survival can be achieved. Conversely, when optimal care is not provided, outcomes can be far worse. Anecdotally, patients who contact CF and participants of a Facebook group for chordoma survivors commonly report that they have received inappropriate care. Moreover, many physicians at high-volume referral centers describe seeing patients after their care was previously mismanaged. Though the actual frequency of suboptimal care for chordoma patients is not known, results of a 2014 community-needs assessments survey completed by over 700 patients and caregivers hint at the magnitude of the problem: 24% report misdiagnosis, 38% report delayed diagnosis, and 18% report receiving inappropriate care.

CF aims to help improve the level of care provided to chordoma patients to give them the best possible chance of a good outcome. Specifically, the Foundation’s goals are to ensure that more patients receive:

• Timely and accurate diagnosis

• Referral to an experienced medical team

• Evidence-based treatment

• Access to experimental therapies, when appropriate

Better Patient Experience

CF is committed to making the experience of confronting chordoma easier and less detrimental for patients and those who care for them. As evidenced by results of the abovementioned needs assessment, the chordoma patient community faces a multitude of medical, emotional, and practical challenges ( Table 41.1 ). Notably, caregivers tend to bear these challenges to an even greater degree than the patients do. To reduce this burden, CF aims to help both patients and caregivers overcome and, ideally, avoid whatever challenges they may face throughout their journey with chordoma. Importantly, CF also strives to give those affected by chordoma opportunities to be a part of the solution by participating in research, volunteering, contributing philanthropically, and/or providing support to peers.

Research

CF accelerates the search for better treatments by catalyzing research across every stage of the treatment-development process, from basic science through clinical research. The Foundation does this through three complementary approaches:

• Uniting and strengthening the research community

• Investing proactively in high-impact research

• Sharing data and biological resources

All of the Foundation’s research efforts are guided by a comprehensive Research Roadmap that defines specific research objectives and strategies to achieve them. The overall strategy embodied in this roadmap is to help identify and advance a pipeline of promising treatment approaches, ultimately culminating in the discovery of treatments demonstrated to be safe and effective for chordoma patients. It is based on the premise that multiple new treatments will likely be required to fully address the clinical need of chordoma patients, and that these treatments could take many forms, such as enhanced surgical techniques, radiotherapy, immune therapy, targeted therapy, or combinations thereof. Moreover, it anticipates that better treatments may be found by repurposing existing therapies, or may require shepherding the development of new therapies, depending on what is learned about the biology of the disease.

The roadmap encompasses five stages of research, each a critical part of the treatment-development process. Research in each stage is necessary, but not sufficient. To succeed in finding better treatments, and, ultimately, a cure, progress at all stages is needed ( Fig. 41.1 )

• Resource Development : Create the biological materials, disease models, and tools needed to enable important experiments.

• Target Discovery : Generate knowledge about the characteristics and vulnerabilities of chordoma that could be exploited as targets for treatment.

• Therapeutic Discovery : Discover new therapies against important targets in chordoma.

• Preclinical Research : Test promising therapies in biologically relevant disease models.

• Clinical Research : Study the safety, efficacy, and comparative effectiveness of promising treatments in chordoma patients.

The Research Roadmap was crafted and is regularly updated based on guidance from the Foundation’s SAB and MAB, and input from other chordoma researchers and subject matter experts. As knowledge about chordoma accumulates and new technologies emerge, priorities are updated to address new needs and opportunities.

Uniting and Strengthening the Research Community

The task of developing better treatments for chordoma requires the contributions of investigators possessing a wide range of knowledge and capabilities corresponding to the entire treatment-development continuum. Moreover, many important advances in chordoma research will only be possible through collaboration among investigators with complementary ideas or resources. Thus, CF aims to create a chordoma research community that includes the full complement of necessary expertise, and to facilitate coordination and collaboration among its members.

When CF started in 2007, the field of chordoma research was in its infancy. Few investigators were actively studying chordoma, and those who were worked in isolation. The Foundation’s first priorities were to bring together investigators interested in chordoma, and to recruit additional experts into the nascent field. To that end, in 2007, the Foundation partnered with the National Institutes of Health (NIH) to organize the First International Chordoma Research Workshop, held in Bethesda, MD. It was attended by over 50 scientists and clinicians—roughly half of whom had not previously studied chordoma, but possessed relevant expertise or interests. This marked the first time researchers interested in chordoma had ever gathered in one place, and, for nearly everyone in attendance, provided their first opportunity to interact with others studying chordoma. This first workshop had three main outcomes. First, it identified key unanswered questions and a set of research priorities around which the field could organize. These priorities formed the basis for the first iteration of the Foundation’s Research Roadmap. Second, it stimulated new ideas and inspired participants to launch a wave of new research projects. Third, it started relationships among participants, many of whom went on to collaborate in various ways. Since then, the Foundation has continued working to connect the global research community through a series of progressively larger International Chordoma Research Workshops, as well as various topic-specific meetings in the United States and Europe. In total, more than 300 investigators have attended CF research meetings.

Over time, CF has continually worked to generate more interest in chordoma and attract new researchers to the field. This has involved networking with investigators at leading academic medical centers, research institutes, and pharmaceutical companies, and exploring specific ways in which their expertise and interests are aligned with opportunities in chordoma research. For example, since the transcription factor brachyury was identified as a key driver and potential therapeutic target of chordoma, CF has worked to attract the interest of scientists who focus on developing drugs against transcription factors—a traditionally difficult class of drug targets. CF has also taken steps to lower barriers for investigators to enter the field by generating, organizing, and sharing biological materials and data commonly needed to embark on chordoma research (described below in greater detail).

Through these efforts, CF has become a central node in the chordoma research network, a position that enables it to facilitate information flow and collaboration among researchers within disconnected islands in the network who would not otherwise interact (e.g., developmental biologists and pathologists). Moreover, by staying in touch with researchers in this network, CF is able to maintain a bird’s eye view of much of the progress happening in the field. As a result, when researchers come to CF with questions, ideas, or challenges, CF is often able to connect them with others in the community who are in a position to help.

The effects of these efforts to strengthen the research community are quantifiable. The Foundation’s database has grown to include over 400 investigators involved in chordoma research. Additionally, surveys of participants who attended International Chordoma Research Workshops indicate that the field is becoming more interconnected. For example, in the year after attending the 2011 research workshop, participants reported a total of 174 new relationships and 30 new collaborations. Additionally, network density (proportion of all possible relationships actually established) increased and average path length (the number of steps between any two individuals in the network) decreased ( Table 41.2 ). These findings are important because each instance of collaboration represents work that might otherwise not have been possible, and each relationship represents the potential for future collaborations. Additionally, studies of scientific networks have demonstrated that higher network density and lower characteristic path length are associated with increased innovation within the network.

The increase in the size and interconnectedness of the chordoma research community has coincided with a significant increase in research activity and new knowledge about the disease. As the field continues to grow, serving as a central node in the chordoma research network will become an increasingly significant function for the Foundation. Additionally, as the edges of knowledge about chordoma continue to expand into new areas and new technologies are developed, CF must continually work to bring investigators with relevant expertise and capabilities into the field. To facilitate this continued development of the community, the Foundation envisions an online research forum for chordoma modeled after Alzforum ( www.alzforum.org ) to enable more frequent interaction among chordoma researchers, and to provide an easy entry point for investigators new to the field.

Investing in High-Impact Research

Rather than simply reacting to requests for funding, as is typical among many disease research foundations, CF proactively initiates and supports research aligned with the objectives defined in its Research Roadmap. Recognizing that achieving many of those objectives will require resources on a scale beyond its means, CF invests strategically with a focus on programs and projects that can leverage or unlock resources or capabilities from other actors. Specifically, CF prioritizes research that enables and encourages researchers or companies to bring their resources to bear on chordoma and/or include chordoma in their ongoing research efforts.

CF invests in research through multiple programs and funding mechanisms, each designed to match specific needs and constraints of different types of research. This includes grants to support both investigator-initiated proposals as well as invited proposals focused on achieving specific research objectives. It also includes prizes, contract research, and strategic partnerships, as the circumstances dictate. Since 2007, the Foundation has invested over $5 million in research, including grants and prizes to over 30 investigators. Below is an overview of the programs and support mechanisms by which the Foundation advances research at each stage of the treatment-development process, as well as notable outcomes from each.