Tumor microenvironment phenotypes and survival in fibrolamellar carcinoma: An exploratory study.

4150 Background: Fibrolamellar carcinoma (FLC) is a very rare liver cancer affecting children, adolescents, and young adults. FLC is characterized by a robust immune tumor microenvironment (TME), but the clinical relevance of TME phenotypes is unknown. Methods: This de-identified study was approved by the Genetic Alliance Organization Institutional Review Board (IRB #IRB00003999). Subjects consented under XCELSIOR: A Patient-Centric Platform Study for Precision Oncology (NCT03793088). From this database, FLC TMEs were classified using the BostonGene framework into immune–stromal subtypes: fibrotic (F), immune desert (ID), immune-enriched fibrotic (IE-F), and immune-enriched non-fibrotic (IE-NF), and further dichotomized into immune-active (IE-F, IE-NF) and immune-cold (F, ID) groups. Associations were assessed using chi-square and non-parametric tests. Overall survival (OS) and time to first progression (TTP1) were evaluated using Kaplan–Meier methods and log-rank tests. Results: Forty-seven subjects (21 females, mean age 20.7 years) were included. TME subtype distribution was: F 46.8%, ID 17.0%, IE-F 21.3%, and IE-NF 14.9%. TME phenotypes were not associated with sex (p = 0.15) or age at diagnosis (p = 0.81). During a median follow-up of 3.7 years, 20 deaths (42.6%) occurred. Median overall survival (OS) for the entire cohort was 75.1 months. Median OS by TME subtype were: F 58.8 months, ID not-reached, IE-F 54.6 months, and IE-NF 75.1 months. Median OS was 86.0 months in the immune-cold group and 54.6 months in the immune-active group (log-rank p = 0.69). Conclusions: In this preliminary analysis with uncompleted dataset of FLC, immune–cold TME phenotypes were not significantly associated with overall survival, although trends toward improved outcomes were observed in immune-active subtypes. These findings should be interpreted as hypothesis-generating due to small numbers. Larger data are needed to clarify the prognostic role of the TME in FLC. Tumor microenvironment subtypes and clinical outcomes in fibrolamellar carcinoma. TME group N (%) Female (n, %) Median age (years, IQR) Deaths (n, %) Median OS (months, 95% CI) Fibrotic (F) 22 (46.8) 12 (57.1) 20.2(17.2–23.8) 12 (60.0) 58.8(43.1–74.5) Immune Desert (ID) 8 (17.0) 5 (23.8) 20.1(17.2–27.7) 1 (5.0) Not reached Immune-cold (F + ID) 30 (63.8) 17 (81.0) 20.2 (17.3–23.8) 13 (65.0) 86.0 (43.0–129.0) Immune-Enriched Fibrotic (IE-F) 10 (21.3) 3 (14.3) 16.1(12.1–28.1) 4 (20.0) 54.6(41.1–68.2) Immune-Enriched Non-Fibrotic (IE-NF) 7 (14.9) 1 (4.8) 18.9(17.7–23.6) 3 (15.0) 75.1(36.6–113.6) Immune-active (IE-F + IE-NF) 17 (36.2) 4 (19.0) 18.7 (13.8–25.0) 7 (35.0) 54.6 (26.2–83.1) Total 47 (100.0) 21 (100.0) 20.1(16.7–23.6) 20 (42.6) 75.1(43.4–106.8) Abbreviations: TME, tumor microenvironment; IQR, interquartile range; OS: overall survival, CI: confidence interval. Note: Percentages are calculated within columns.<