Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics

Leonardo G Da Fonseca; Victor Junji Yamamoto; Mateus Trinconi Cunha; Giovanna Sawaya Torre; Raphael L C Araujo; Gilton Marques Fonseca; Andre Tsin Chih Chen; Aline Lopes Chagas; Paulo Herman; Venancio Avancini Ferreira Alves; Flair Jose Carrilho

doi:10.2147/JHC.S428741

Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics

J Hepatocell Carcinoma. 2023 Nov 1:10:1923-1933. doi: 10.2147/JHC.S428741. eCollection 2023.

Affiliations

¹ Department of Medical Oncology, ICESP - Instituto do Cancer DO Estado de Sao Paulo, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
² Department of Radiology, ICESP - Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
³ Digestive Surgery Division, Department of Surgery, Universidade Federal de São Paulo, São Paulo, Brazil.
⁴ Digestive Surgery Division, Department of Gastroenterology, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
⁵ Radiation Oncology Department - Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
⁶ Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.
⁷ Department of Pathology, LIM-14, Hospital das Clinicas, University of São Paulo School of Medicine, São Paulo, Brazil.

^# Contributed equally.

Abstract

Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors.

Patients and methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters.

Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93).

Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.

Keywords: fibrolamellar carcinoma; liver cancer; radiomics; rare tumors; systemic treatment.