Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study

BackgroundEvidence-based treatment for unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not been established. This study aimed to assess the effectiveness and safety of interventional treatment combined with immunotargeted therapy (IIT) in unresectable cHCC-CCA patients.Methods...

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Main Authors: Yan-Song Lin, Li-Yan Wu, Li-Hui Lin, Xia Yang, Fang-Yi Liu, Yan-Qin Wu, Zhen Ding, Yu-Jing Liang, Jing-Ping Yun
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591127/full
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author Yan-Song Lin
Yan-Song Lin
Li-Yan Wu
Li-Yan Wu
Li-Hui Lin
Xia Yang
Xia Yang
Fang-Yi Liu
Fang-Yi Liu
Yan-Qin Wu
Zhen Ding
Yu-Jing Liang
Yu-Jing Liang
Jing-Ping Yun
Jing-Ping Yun
author_facet Yan-Song Lin
Yan-Song Lin
Li-Yan Wu
Li-Yan Wu
Li-Hui Lin
Xia Yang
Xia Yang
Fang-Yi Liu
Fang-Yi Liu
Yan-Qin Wu
Zhen Ding
Yu-Jing Liang
Yu-Jing Liang
Jing-Ping Yun
Jing-Ping Yun
author_sort Yan-Song Lin
collection DOAJ
description BackgroundEvidence-based treatment for unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not been established. This study aimed to assess the effectiveness and safety of interventional treatment combined with immunotargeted therapy (IIT) in unresectable cHCC-CCA patients.MethodsPatients with a histological diagnosis of unresectable cHCC-CCA who received IIT therapy from January 2019 to March 2024 were retrospectively enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), tumor responses and safety.ResultsA total of 242 cHCC-CCA patients were screened and 51 patients were enrolled for analysis. The median follow-up duration was 15.8 months (95% CI: 12.0-19.7 months). The median OS was 17.8 months (95% CI: 12.4-23.2 months) and the median PFS was 8.9 months (95% CI: 5.8-12.0 months). For overall response, the objective response rate was 41.2% and 56.9% based on RECIST 1.1 and mRECIST, respectively. Patients with primary cHCC-CCA showed significantly prolonged OS (median OS: 21.4 months vs. 11.4 months, p = 0.011) and PFS (median PFS: 9.5 months vs. 4.1 months, p = 0.036) compared to those with recurrent cHCC-CCA. Patients with dominant HCC did not show significant differences for OS (p = 0.835) and PFS (p = 0.553) compared to those with dominant iCCA. Six patients (11.8%) experienced grade ≥3 adverse events, including leukopenia (n=1, 2.0%), neutropenia (n=1, 2.0%), thrombocytopenia (n=2, 3.9%), elevated alanine transaminase (ALT) (n=2, 3.9%), elevated aspartate aminotransferase (AST) (n=2, 3.9%), hypoalbuminemia (n=2, 3.9%), and hyperbilirubinemia (n=1, 2.0%). Immunotherapy was discontinued for two patients due to grade ≥3 elevations in ALT and AST.ConclusionThe triple combination of interventional treatment, PD-(L)1 inhibitor, and targeted therapy is an effective and safe approach for unresectable cHCC-CCA patients.
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spelling doaj-art-f33db750b3fe4db7ae84330aeb7123de2025-08-20T02:37:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15911271591127Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort studyYan-Song Lin0Yan-Song Lin1Li-Yan Wu2Li-Yan Wu3Li-Hui Lin4Xia Yang5Xia Yang6Fang-Yi Liu7Fang-Yi Liu8Yan-Qin Wu9Zhen Ding10Yu-Jing Liang11Yu-Jing Liang12Jing-Ping Yun13Jing-Ping Yun14State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackgroundEvidence-based treatment for unresectable combined hepatocellular-cholangiocarcinoma (cHCC-CCA) has not been established. This study aimed to assess the effectiveness and safety of interventional treatment combined with immunotargeted therapy (IIT) in unresectable cHCC-CCA patients.MethodsPatients with a histological diagnosis of unresectable cHCC-CCA who received IIT therapy from January 2019 to March 2024 were retrospectively enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), tumor responses and safety.ResultsA total of 242 cHCC-CCA patients were screened and 51 patients were enrolled for analysis. The median follow-up duration was 15.8 months (95% CI: 12.0-19.7 months). The median OS was 17.8 months (95% CI: 12.4-23.2 months) and the median PFS was 8.9 months (95% CI: 5.8-12.0 months). For overall response, the objective response rate was 41.2% and 56.9% based on RECIST 1.1 and mRECIST, respectively. Patients with primary cHCC-CCA showed significantly prolonged OS (median OS: 21.4 months vs. 11.4 months, p = 0.011) and PFS (median PFS: 9.5 months vs. 4.1 months, p = 0.036) compared to those with recurrent cHCC-CCA. Patients with dominant HCC did not show significant differences for OS (p = 0.835) and PFS (p = 0.553) compared to those with dominant iCCA. Six patients (11.8%) experienced grade ≥3 adverse events, including leukopenia (n=1, 2.0%), neutropenia (n=1, 2.0%), thrombocytopenia (n=2, 3.9%), elevated alanine transaminase (ALT) (n=2, 3.9%), elevated aspartate aminotransferase (AST) (n=2, 3.9%), hypoalbuminemia (n=2, 3.9%), and hyperbilirubinemia (n=1, 2.0%). Immunotherapy was discontinued for two patients due to grade ≥3 elevations in ALT and AST.ConclusionThe triple combination of interventional treatment, PD-(L)1 inhibitor, and targeted therapy is an effective and safe approach for unresectable cHCC-CCA patients.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591127/fullinterventional treatmentPD-(L)1 inhibitortargeted therapyunresectable combined hepatocellular-cholangiocarcinomaoutcome
spellingShingle Yan-Song Lin
Yan-Song Lin
Li-Yan Wu
Li-Yan Wu
Li-Hui Lin
Xia Yang
Xia Yang
Fang-Yi Liu
Fang-Yi Liu
Yan-Qin Wu
Zhen Ding
Yu-Jing Liang
Yu-Jing Liang
Jing-Ping Yun
Jing-Ping Yun
Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
Frontiers in Immunology
interventional treatment
PD-(L)1 inhibitor
targeted therapy
unresectable combined hepatocellular-cholangiocarcinoma
outcome
title Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
title_full Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
title_fullStr Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
title_full_unstemmed Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
title_short Interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular-cholangiocarcinoma: a real-world retrospective cohort study
title_sort interventional treatment combined with immunotargeted therapy in unresectable combined hepatocellular cholangiocarcinoma a real world retrospective cohort study
topic interventional treatment
PD-(L)1 inhibitor
targeted therapy
unresectable combined hepatocellular-cholangiocarcinoma
outcome
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1591127/full
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