Draft:Fibrolamellar Registry

The Fibrolamellar Registry is a 501(c)(3) non-profit organization in the United States established by patients and family members of patients with Fibrolamellar Hepatocellular Carcinoma (FLC) to bring together patients, family members, scientists and clinicians. http://www.fibroregistry.org

The Fibrolamellar Registry approach offers a number of advantages afforded through governance by patients and family members, and by not being affiliated with one hospital : The registry follows patient outcomes, even if the patient transfers institutions and/or clinical assessment is complete. This allows studies of longer term outcomes. By following patient outcomes, data can be edited to include potential re-evaluation of diagnosis and/or additional molecular characterization as it becomes available. At the core of the registry database is a collection of hundreds of questions designed by patients and family members, with input from oncologists, surgeons, pathologists, and hepatologists. The comprehensive questionnaire goes far beyond questions covered in standard medical records. The core is currently expanding to start including data from the patient health records.

Activities
One major activity is making science accessible to the patients. The Fibrolamellar Registry has plain language summaries of science articles about fibrolamellar (https://fibroregistry.org/published-papers/ ). There are also videos about some of the article but also a video tutorial on how to search PubMed (https://fibroregistry.org/browse-pubmed/), a site developed by the NIH to make the published science literature available for all.

Another major activity is to make data on fibrolamellar carcinoma available for a wider research clinical community. The Fibrolamellar Registry, started with the creation of a questionnaire with 600 queries that go beyond the standard health record. In 2022 the data was migrated over to RedCap to make increase its accessibility.

Accomplishments
The Fibrolamellar registry now has data on 250 patients from over 20 countries. Based on data in the registry, four articles were published in 2022-2023 in peer reviewed science journals.

The data in the Fibrolamellar Registry was used for a deep dive into a study of the outcomes of fibrolamellar patients in "Clinical and demographic predictors of survival for fibrolamellar carcinoma patients-A patient community, registry-based study", by Amichai Berkovitz.

A specific kind of immunological intervention is called “Immune checkpoint inhibitors”. The fibrolamellar registry put out a request and found 30 patients, across institutions, who had received these treatments. The Registry de-identified the records and provided them to a team of radiologists and oncologists for assessment. The results were published in "Clinical Outcomes in Fibrolamellar Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors".

Many fibrolamellar patients are affected by high levels of ammonia. High ammonia can lead to confusion, or even coma and/or death. The Fibrolamellar registry put out a call to patients who had problems with high ammonia. The results contributed to a study of the changes in the proteins and metabolism of fibrolamellar in “Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma” by Solomon Levin, et al.

To bring a new drug to the clinic can take a long time requiring extensive studies in other animals, preclinical studies, and then safety studies in other animals and then humans. One faster route to bring drugs to the clinical to treat a disease is to do functional studies to find drugs that can be “repurposed”. Such a drug-repurposing screen found success for a number of therapeutics that was not previously predicted. A follow-up study found specific combinations of drugs that were effective on tumors of fibrolamellar hepatocellular carcinoma that were implanted in mice. From an exploration of the Fibrolamellar Registry it was found that some patients had received some of these agents in single isolated tests. The results from The Fibrolamellar Registry supported the results from the studies in mice, and were included in a publication: "Targeting BCL-XL in fibrolamellar hepatocellular carcinoma" by Shebl et al. The work is currently being developed for a clinical trial.