‘Think tank’ of multidisciplinary experts develop proposals to leverage precision medicine in improving cholangiocarcinoma patient outcomes

Twenty-nine expert scientists and clinicians from the world's leading academic institutions developed potentially transformative project proposals while gathered in Las Vegas for a two-day think tank meeting called, Cure Cholangiocarcinoma Think Tank (C2T2). A white paper summarizing the critical discussion themes and proposed projects from the May 12-14 working meeting outlines specific next steps for the community. This effort, made possible by generous philanthropic donations to the Cholangiocarcinoma Foundation, was the first of its kind in the cholangiocarcinoma (CCA) field.

Experts outside the cholangiocarcinoma field were instrumental in helping identify the topics for the C2T2 meeting. The primary themes – precision prevention, early detection, and precision therapeutics – reflected areas of urgency and opportunity for improving outcomes for people impacted by CCA. In both cases, scientific discovery has advanced to the point where addressing knowledge gaps in these two areas could have a measurable and profound impact on the trajectory of CCA.

“The inaugural Cure Cholangiocarcinoma Think Tank (C2T2) meeting was a tremendous success and laid the foundation for innovative approaches to collaborating across institutional boundaries with a total focus on helping patients with the most pressing unmet clinical needs,” said Dr. Mitesh J. Borad, chair of the International Cholangiocarcinoma Research Network (ICRN).

“The outputs from this year's meeting will galvanize the already robust efforts in precision medicine to facilitate earlier diagnosis and more tailored treatments for individual patients. We look forward to releasing a white paper summarizing the meeting proceedings and sharing it with the cholangiocarcinoma research community,” he added.

Cholangiocarcinoma is a type of cancer that forms in the slender tubes called bile ducts that carry the digestive fluid bile. Bile ducts connect the liver to the gallbladder and the small intestine. An estimated 10,000 Americans are diagnosed yearly with the lethal cancer with a poor prognosis and high mortality rate. A recent study (JAMA Network Open) forecasts that by 2040, liver and bile duct cancer will be the third deadliest cancer in the United States. This startling statistic invokes immediate action to achieve a cure for CCA, which C2T2 is dedicated to doing by addressing its challenges.

Key takeaways from the C2T2 meeting focused on overcoming such challenges presented by the low incidence of CCA, including difficulty in completing early detection studies and developing a screening test that can be sufficiently specific. Most early detection tests are refined through a case-controlled study. Those factors resulted in the agreement to identify a very high-risk group of patients, such as young patients with Primary Sclerosing Cholangitis (PSC) or patients with a genetic predisposition for CCA, or seek to include CCA as part of a multi-cancer test.

Furthermore, the CCA field should work to ensure that CCA is included within these studies for a multi-cancer test and that these tests are pre-specified to predict CCA. Preliminary data is needed to show a meaningful result in a rare cancer like CCA. Identifying a genetic predisposition or other risk groups, including real-life controls, and conducting prospective studies to define the performance of the test are also needed.

Additional points included the need to understand tumor biology better and more effectively guide where researchers look for treatment targets based on what is found in a tumor at the genomic level. Using a multi-step approach to evaluate tissue and looking at relevant proximal body fluids such as bile or stool was also recognized. Challenges with bile include the need for an invasive procedure. It is hard to work with at the protein level, and stents can confound. Evaluating whether it might be possible to use the colonoscopy to gather bile was contemplated.

Additional key takeaways in the white paper are:

• Preliminary data are needed to show a meaningful result in rare cancer like CCA. Identify a genetic predisposition or other risk groups, include real-life controls, and conduct prospective studies to define the performance of the test.
• CCA can learn from other cancers, such as pancreatic and lung, where high-risk groups (e.g., adult-onset diabetes or smokers, respectively) are identified and screened. What would the best CCA corollary be?
• We need to understand the biology by guiding where we look based on what we find in the tumor at the genomic level. Use a multi-step approach, starting with evaluating tissue and then looking at relevant, proximal body fluids such as bile or stool.
• Challenges with bile include the need for an invasive procedure, bile is hard to work with at the protein level, and stents can be confounders. Evaluate whether it might be possible to use the colonoscopy to gather bile.

“The C2T2 meeting was much-anticipated. It was enormously beneficial to have invited specialists from outside our research community to share their best practices, innovations and new methodologies,” said CCF CEO and Founder Stacie Lindsey. “The group labored together for two days to define concrete projects to move the science forward in meaningful ways. We are excited to see these projects advancing rapidly.”

C2T2 was not a typical academic gathering designed around a series of didactic talks, data sharing, and discussions around broad themes. The multi-disciplinary group of experts that came together for the meeting remains committed to developing research proposals designed to answer concrete questions and advance near-term impact. Because of the leadership of the Foundation and key donors, the projects emerging from the meeting will have seed funding support and be the subject of additional, focused fundraising efforts.

“For the first time in rare cancer like cholangiocarcinoma, we put together a summit to gather experts from inside and outside the field to work together productively to solve major challenges in the care of these patients. One major focus is how we can predict patients with primary sclerosing cholangitis, a high-risk disease of cholangiocarcinoma, who will develop cholangiocarcinoma,” said Dr. Nilo Azad, an associate professor of oncology and a member of the Gastrointestinal Oncology Program within the Sidney Kimmel Comprehensive Cancer Center.

She continued, “We have been able to leverage generous philanthropic support along with tools developed by the cholangiocarcinoma Foundation and major research institutions around the world to come together to profile biospecimens in the hopes of really understanding which patients most likely develop this cancer. This could result in meaningful improvement in the survival of these patients by catching things early.”

C2T2 is planning subsequent meetings with outcomes anticipated to benefit current and future CCA patients, caregivers and their loved ones. Developments to improve methods of early detection, advance treatment options and improve the quality of life and overall survival of patients are a C2T2 priority.

The white paper can be downloaded at https://cholangiocarcinoma.org/cure-cholangiocarcinoma-think-tank-c2t2/