Use of a nationwide, patient-powered observational platform to define the landscape of treatment, molecular profiling, and outcomes for fibrolamellar carcinoma.
Authors: Paul Kent, Alaa Awawda, Hiba Kouser, Alanis Sabates, Zachariah D. Cole, Mark Adam Shapiro, Tom Stockwell, Timothy Joseph Stuhlmiller
Journal: Journal of Clinical Oncology (2024)

e16192 Background: Fibrolamellar carcinoma (FLC) is a rare form of liver cancer, distinct from hepatocellular carcinoma, characterized by its prevalence among adolescents and young adults, capacity to form bulky tumors, and high rate of recurrence and metastasis. Without an established standard-of-care, the treatment of FLC is multidisciplinary, often involving surgery, radiation, and therapeutic interventions concurrently. Understanding the landscape of real-world treatments for FLC pts is imperative to defining an effective therapeutic approach. Methods: In partnership with the FibroFighters Foundation, we enrolled 102 patients (pts) in the observational research protocol XCELSIOR ( NCT03793088 ). Electronic medical records (EMR) were gathered from over 2,000 sites of care across 31 states - a median of 43 unique locations per pt - and utilized to populate a 21 CFR Part 11-compliant database with fully longitudinal, uninterrupted clinical data. Data elements were standardized to OMOP-based dictionaries. Anti-cancer medications were combined to define regimens and correlated with surgical dates. Pts were offered access to aggregated EMR and structured summaries as a digital personal health record via online portals. Results: Median age at diagnosis was 19 years (range 6-51 years) and median diagnosis date was 8/26/2020. At initial diagnosis, 36% of pts had distant metastases, but 86% of all pts eventually experienced metastatic disease with lung being the most frequent location (30 pts). The most prevalent anti-cancer therapies used were lenvatinib (75% pts exposed) and nivolumab (73% pts) and the most prevalent regimen was gemcitabine/lenvatinib/oxaliplatin (33% of pts). Among repurposed agents, 50% were exposed to quercetin, 44% to celecoxib, and 14% to metformin. 64% of pts underwent at least one surgical resection with 21% of these receiving neoadjuvant therapy including 7 distinct regimens, most commonly gemcitabine/lenvatinib/oxaliplatin. 91% of pts received adjuvant therapy for a median duration of 162 days. 22% of pts received radiation therapy and 15% received Y90 radioembolization. Among diagnostic profiling, 82% had somatic next generation sequencing, 48% had germline testing, 28.5% had organoid functional profiling, and 68% had Signatera testing performed. Conclusions: Patients with FLC undergo extensive molecular profiling with multiple novel therapeutic regimens being employed in real world practice. Aggregation of raw imaging scans is ongoing for central radiological review to measure depth and duration of response offered by the recorded therapeutic strategies. This dataset is a rich resource available to academic and government researchers to fuel research and define optimal treatment modalities. Topline statistics for the dataset are available at https://xcures.com/flcdashboard/ . Clinical trial information: NCT03793088 .