Curated Papers > In recent years, there has been significant research on "CRISPR gene editing" with high impact (IF≥30, over the past five years).

Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians.

Literature Information

DOI	10.3322/caac.21759
PMID	36260350
Journal	CA: a cancer journal for clinicians
Impact Factor	232.4
JCR Quartile	Q1
Publication Year	2023
Times Cited	225
Keywords	chemotherapy, immunotherapy, intrahepatic cholangiocarcinoma, locoregional therapies
Literature Type	Journal Article, Review
ISSN	0007-9235
Pages	198-222
Issue	73(2)
Authors	Dimitrios Moris, Manisha Palta, Charles Kim, Peter J Allen, Michael A Morse, Michael E Lidsky

TL;DR

Intrahepatic cholangiocarcinoma (ICC) is a highly fatal liver malignancy with limited curative options, as only 20%-30% of patients are surgical candidates, and systemic therapies yield approximately one year of survival for the majority. Recent advancements in treatment strategies, including the emergence of triplet chemotherapy, immunotherapy combinations, and targeted molecular therapies, aim to enhance outcomes, highlighting the need for a personalized and multidisciplinary approach in managing this challenging disease.

Search for more papers on MaltSci.com

chemotherapy · immunotherapy · intrahepatic cholangiocarcinoma · locoregional therapies

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.

MaltSci.com AI Research Service

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas

Locate StatementsFind traces of a specific claim within the paper

Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed

1. What are the potential benefits and risks of integrating immunotherapy with traditional chemotherapy for intrahepatic cholangiocarcinoma?
2. How do recent advancements in molecular therapies compare to traditional systemic therapies in terms of efficacy and patient outcomes for ICC?
3. What criteria should clinicians use to determine eligibility for novel treatment combinations, such as triplet regimens or locoregional therapies, in ICC patients?
4. How does the emerging role of targeted therapies influence the future treatment landscape for intrahepatic cholangiocarcinoma?
5. In what ways can a multidisciplinary approach improve the management and outcomes for patients with locally unresectable intrahepatic cholangiocarcinoma?

Key Findings

1. Research Background and Purpose: Intrahepatic cholangiocarcinoma (ICC) is recognized as the second most prevalent primary liver tumor and is associated with a poor prognosis, making it a significant clinical challenge. The primary objective of this overview is to elucidate the current therapeutic landscape for ICC, highlighting advancements in treatment modalities, and to discuss future directions for improving patient outcomes. The review aims to summarize existing literature on treatment strategies and propose a personalized, multidisciplinary approach to managing this aggressive malignancy.

2. Main Methods and Findings: The review synthesizes key findings from recent research on ICC therapies, focusing on surgical, systemic, and locoregional treatment options. Notably, surgical resection remains the sole potentially curative approach, applicable to only 20%-30% of patients. Among those who undergo resection, the addition of adjuvant capecitabine has shown to extend median survival to approximately 53 months. For the majority of patients with unresectable or metastatic disease, systemic therapies remain the cornerstone of treatment. The longstanding doublet chemotherapy regimen of gemcitabine and cisplatin has been the standard first-line treatment; however, newer triplet regimens and immunotherapy strategies are emerging as potential game-changers. Recent approvals of molecular therapies targeting fibroblast growth factor receptor and isocitrate dehydrogenase for second-line treatment cater to a subset of patients with actionable genomic alterations. Moreover, combining systemic therapies with locoregional interventions, such as radioembolization and hepatic artery infusion, has demonstrated promise in delaying disease progression.

3. Core Conclusions: The review concludes that while surgical resection provides the best outcomes for early-stage ICC, the treatment paradigm is evolving for advanced cases. The introduction of triplet chemotherapy regimens and immunotherapy, particularly the combination of durvalumab with standard cytotoxic agents, shows improved survival rates and may redefine first-line therapy strategies. The potential for molecular therapies in first-line settings is also a critical area of ongoing exploration.

4. Research Significance and Impact: This review underscores the urgent need for continued innovation in the treatment of ICC, given its high mortality rate and limited therapeutic options for advanced disease. By detailing the current and emerging treatments, the review provides clinicians with a comprehensive understanding of available strategies and emphasizes the importance of personalized medicine. The proposed multidisciplinary treatment algorithm aims to optimize patient care and improve survival outcomes, highlighting the significance of tailored approaches in complex malignancies like ICC. This work contributes to the broader oncological discourse, advocating for the integration of new therapies and the refinement of existing protocols to enhance patient quality of life and survival.

Literatures Citing This Work

1. The Application of Artificial Intelligence to Investigate Long-Term Outcomes and Assess Optimal Margin Width in Hepatectomy for Intrahepatic Cholangiocarcinoma. - Laura Alaimo;Zorays Moazzam;Yutaka Endo;Henrique A Lima;Swatika P Butey;Andrea Ruzzenente;Alfredo Guglielmi;Luca Aldrighetti;Matthew Weiss;Todd W Bauer;Sorin Alexandrescu;George A Poultsides;Shishir K Maithel;Hugo P Marques;Guillaume Martel;Carlo Pulitano;Feng Shen;François Cauchy;Bas Groot Koerkamp;Itaru Endo;Minoru Kitago;Alex Kim;Aslam Ejaz;Joal Beane;Jordan Cloyd;Timothy M Pawlik - Annals of surgical oncology (2023)
2. Intrahepatic Cholangiocarcinoma-Where Are We Now and Where Are We Going to? - Michał P Wasilewicz;Rafał Becht - Medicina (Kaunas, Lithuania) (2023)
3. MMP14 is a diagnostic gene of intrahepatic cholangiocarcinoma associated with immune cell infiltration. - Jun Wu;Yang Guo;Zhi-Fan Zuo;Zi-Wei Zhu;Lei Han - World journal of gastroenterology (2023)
4. Identification and validation of a plasma metabolomics-based model for risk stratification of intrahepatic cholangiocarcinoma. - Jiehui Tan;Man Shu;Junbin Liao;Ruiming Liang;Shiyi Liu;Ming Kuang;Sui Peng;Han Xiao;Qian Zhou - Journal of cancer research and clinical oncology (2023)
5. An age-group analysis on the efficacy of chemotherapy in older adult patients with metastatic biliary tract cancer: a Japanese cancer registry cohort study. - Takeru Hirao;Kenji Ikezawa;Toshitaka Morishima;Kazuma Daiku;Yusuke Seiki;Ko Watsuji;Yasuharu Kawamoto;Sena Higashi;Makiko Urabe;Yugo Kai;Ryoji Takada;Takuo Yamai;Kaori Mukai;Tasuku Nakabori;Hiroyuki Uehara;Isao Miyashiro;Kazuyoshi Ohkawa - BMC gastroenterology (2023)
6. Letter to the Editor: Comment on "Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma". - Min Wu;Zhichao Chen;Yonghua Lin;Jianfeng Wei - Annals of surgical oncology (2023)
7. Proposal for a new N-stage classification system for intrahepatic cholangiocarcinoma. - Shan Liao;Ruizhe Liao;Huaxing Wu;Shijie Wang;Yanming Zhou - Frontiers in oncology (2023)
8. Case Report: Camrelizumab combined with gemcitabine and oxaliplatin in the treatment of advanced intrahepatic cholangiocarcinoma: a case report and literature review. - Zhongyan Zhang;Xin Wang;Hehe Li;Huimin Sun;Jianhong Chen;Hongfeng Lin - Frontiers in immunology (2023)
9. Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation. - Elishama N Kanu;Kristen E Rhodin;Sabran J Masoud;Austin M Eckhoff;Alex J Bartholomew;Thomas C Howell;Jiayin Bao;Nicholas T Befera;Charles Y Kim;Dan G Blazer;Sabino Zani;Daniel P Nussbaum;Peter J Allen;Michael E Lidsky - Journal of surgical oncology (2023)
10. Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis. - Qiao Ke;Lei Wang;Ziguo Lin;Hongzhi Liu;Jianying Lou;Shuguo Zheng;Xinyu Bi;Jianming Wang;Wei Guo;Fuyu Li;Jian Wang;Yamin Zheng;Jingdong Li;Shi Cheng;Weiping Zhou;Jingfeng Liu;Yongyi Zeng - BMC cancer (2023)

... (215 more literatures)

---

© 2025 MaltSci - We reshape scientific research with AI technology