Clinical and genomic characteristics of hepatocellular carcinoma-cholangiocarcinoma: Insights from real-world data.
Authors: Abidoye Oluseyi , Chang Isabela , Hoyek Celine , Pirozzi Angelo , Okano Naohiro , Zheng-Lin Binbin , Kosiorek Heidi E. , Eslinger Cody , Sonbol Mohamad B. , Ahn Daniel H. , Wu Christina , Yoshino Takayuki , Ikeda Masafumi , Morizane Chigusa , Bando Hideaki , Nakamura Yoshiaki , Fujisawa Takao , Shibuki Taro , Borad Mitesh J. , Bekaii-Saab Tanios S. 
Published: January 2025

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Background:
Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare and complex liver cancer with features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), making its management challenging. This study aims to analyze the clinical characteristics, genomic profiles, and treatment outcomes of cHCC-CCA patients in a real-world setting.
Methods:
We conducted a retrospective analysis of cHCC-CCA patients across three first-line treatment groups: chemotherapy alone(Gemcitabine/Cisplatin, FOLFOX), HCC-directed therapies (atezolizumab/bevacizumab, lenvatinib, nivolumab, durvalumab, sorafenib), and chemoimmunotherapy (Gemcitabine/Cisplatin combined with immunotherapy). This international study, involving Mayo Clinic and the National Cancer Center East (Japan), assessed overall survival (OS) using Kaplan-Meier and Cox regression models.
Results:
A total of 68 patients were included, with a mean age of 66 years; 74% were male and 66% were White Non-Hispanics. Cirrhosis was present in 74% of patients at diagnosis, and Hepatitis B and C were common etiologies in 57%. Prior primary resection and regional therapies (Transarterial chemoembolization (TACE), Transarterial radioembolization (TARE)) were recorded in 39% and 50% of patients, respectively. Advanced/metastatic disease was present in 52% of the cohort. The distribution of first-line treatments was as follows: 47% received chemotherapy alone, 39% received HCC-directed therapy, and 14% received chemoimmunotherapy. Genomic alterations were detected in 44% patients, with
TP53
(28%),
ARID1A
(25%), and
TERT
(22%) being the most frequent. The HCC-directed therapy group demonstrated the best overall response rate (52%) and had a median OS of 15.8 months (mo), compared to 11.8 mo for chemotherapy and 4.7 mo for chemoimmunotherapy (p=0.8). Patients who received regional treatments had a longer median OS of 15.8 mo compared to those who did not (10.2 mo) (p=0.4).
Conclusions:
HCC-directed therapy showed a trend towards better survival outcomes compared to other treatments, though not statistically significant. A considerable proportion of patients had genomic alterations, which may have influenced survival outcomes. Ongoing research with larger cohorts is underway to further elucidate the impact of genomic variations on treatment efficacy and refine therapeutic strategies for this challenging malignancy.

Baseline characteristics of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA).

Total(N=68)

Mean age at diagnosis, years (SD)
66(6.4)

Gender, n (%)

Male
50 (74%)

Ethnicity, n (%)

White, Non-Hispanic
45 (66%)

Cirrhosis at diagnosis, n (%)
50 (74%)

Etiology of Liver disease, n (%)

Viral (Hepatitis B and C)
39 (57%)

History of Primary resection, n (%)
27 (39%)

Regional treatment, n (%)
34 (50%)

Afp, n (%)

< 200
23 (64%)

ca19_9, n (%)

< 50
27 (82%)