Pusan National University researchers identify potential new second-line option for advanced biliary tract cancer

Biliary tract cancers, including intrahepatic, perihilar, and extrahepatic cholangiocarcinoma and gallbladder cancer, are among the most aggressive gastrointestinal malignancies.  Treatment options remain limited once the disease progresses after first-line chemotherapy, and survival rarely exceeds one year.

To address this, the team of researchers led by Professor Yun Hak Kim from Pusan National University, analyzed 12 years of clinical data from 54 patients treated at Yonsei Severance Hospital and combined the results with a systematic review and meta-analysis of 21 studies from around the world. This paper was made available online on 05 September 2025 in the journal International Journal of Surgery.

The combined evidence suggests that FOLFIRINOX may provide better progression-free and overall survival than currently recommended regimens such as FOLFOX, FOLFIRI, or nal-IRI/FL.

“We conducted a meta-analysis integrating 12 years of real-world data on the use of FOLFIRINOX or mFOLFIRINOX as salvage treatment in patients with advanced BTC treated at the Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, along with all available published studies on second-line chemotherapy regimens for advanced BTC,” said Prof. Kim.

In this study, patients receiving FOLFIRINOX achieved a median progression-free survival of 4.2 months and an overall survival of 11.4 months. In the accompanying meta-analysis of 21 studies, FOLFIRINOX demonstrated numerically longer progression-free and overall survival compared with currently used second-line regimens such as FOLFOX, FOLFIRI, and nal-IRI/FL.

Still, the authors caution that toxicity remains significant. Nearly 40 percent of patients developed severe neutropenia, requiring dose adjustments or additional medical support. The team emphasizes that FOLFIRINOX should be reserved for fit patients under close supervision until further prospective trials confirm its broader safety.

Beyond short-term survival, the study highlights the potential to integrate biomarker-based selection and supportive strategies such as granulocyte colony-stimulating factor to mitigate toxicity. Future research may also explore pairing FOLFIRINOX with immunotherapies or molecular-targeted drugs. “Our findings suggest that FOLFIRINOX may offer a potential benefit as a second-line treatment option for BTC following progression on first-line chemotherapy,” concluded Prof. Kim.

This paper provides an evidence-based foundation for clinicians considering treatment options after first-line chemotherapy failure and may guide updates to future BTC management guidelines.

***

About Pusan National University

Pusan National University, located in Busan, South Korea, was founded in 1946 and is now the No. 1 national university of South Korea in research and educational competency. The multi-campus university also has other smaller campuses in Yangsan, Miryang, and Ami. The university prides itself on the principles of truth, freedom, and service and has approximately 30,000 students, 1,200 professors, and 750 faculty members. The university comprises 14 colleges (schools) and one independent division, with 103 departments in all.

Website: https://www.pusan.ac.kr/eng/Main.do

About the author Professor Yun Hak Kim

Professor Yun Hak Kim is an associate professor in the Department of Anatomy at Pusan National University’s School of Medicine. He serves as the head professor in the Department of Interdisciplinary Science of Genomic Science at PNU. His group utilizes cutting-edge technology to understand the pathophysiology of diseases and to discover novel therapeutic targets. The Kim group handles both experiments and bioinformatics, employing a multiomics approach that includes single-cell transcriptomics, spatial omics, genomics, epigenomics, and microbiomics to unravel the causes of complex diseases.

Lab: https://yunhakkim.pusan.ac.kr/

ORCID id: 0000-0002-9796-8266

About the author Professor Kihun Kim

Dr. Kihun Kim is a Fellow in the Department of Occupational and Environmental Medicine at Pusan National University Yangsan Hospital. He is a physician-scientist whose research spans a wide range of medical and public health fields, with particular interest in the molecular and epidemiological mechanisms of occupational and environmental diseases. After earning his M.D. and Ph.D. from Pusan National University School of Medicine, he has advanced research integrating systematic review, meta-analysis, and genomic bioinformatics to explore disease mechanisms and health determinants across diverse medical domains. His representative works encompass large-scale meta-analyses and genomic studies that have clarified causal relationships between risk factors and various diseases, including occupational and environmental health, cancers, dermatologic disorders, neurological conditions, and metabolic diseases. He has received several academic honors, including the Future Scientist Award, Basic Medical Science Young Investigator Award, and multiple Best Presentation Awards. Through his multidisciplinary approach, Dr. Kim aims to bridge population-based epidemiology and molecular biology to establish evidence-based diagnostic and preventive strategies across the field of medicine.

ORCID id: 0000-0001-6445-6881
 

About Yonsei University

Yonsei University, located in Seoul, South Korea, is one of the nation’s oldest and most prestigious private research institutions. Founded in 1885, the university is renowned for academic excellence and its strong commitment to international collaborations and partnerships. Yonsei offers diverse programs across the humanities, sciences, engineering, business, and more, serving approximately 30,000 students with a distinguished faculty. Yonsei remains dedicated to fostering creativity and cultural exchange in a rapidly evolving world.

https://www.yonsei.ac.kr/en_sc/

About the author Professor Galam Leem

Professor Galam Leem is a Clinical Assitant Professor in the Division of Gastroenterology, Department of Internal Medicine at Severance Hospital, Yonsei University College of Medicine. He is a clinician-scientist specializing in translational cancer research. After earning his M.D. from Yonsei University College of Medicine and board certification in Internal Medicine, he obtained a Ph.D. in Tumor Immunology from the Korea Advanced Institute of Science and Technology (KAIST). Since then, he has been conducting both clinical practice and research at Severance Hospital, focusing on elucidating the molecular mechanisms of tumorigenesis and metastasis in pancreatic, biliary, and gastrointestinal cancers, and developing innovative therapeutic strategies targeting these processes. His work exemplifies the successful integration of clinical insight and basic research, making tangible contributions to improving the survival and quality of life of patients with refractory cancers.

ORCID id: 0000-0001-6490-0911

About the author Professor Seungmin Bang

Professor Seungmin Bang is a Professor in the Division of Gastroenterology, Department of Internal Medicine at Severance Hospital, Yonsei University College of Medicine. Over the past two decades, he has treated pancreatic cancer patients in real clinical settings while conducting translational research to uncover the pathogenesis of the disease and develop novel therapeutic strategies. After earning board certifications in Internal Medicine and Gastroenterology and obtaining a Ph.D. in Clinical Oncology, he has published over 100 scientific papers as a first, corresponding, or co-author. In 2010, he served as a visiting professor at Johns Hopkins University, where he investigated oncogenic mutations in pancreatic cancer. His current research focuses on establishing preclinical models and utilizing genomic approaches to develop precision diagnostics and treatments for pancreatic cancer.

ORCID id: 0000-0001-5209-8351