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ORIGINAL RESEARCH ARTICLE
Patient-derived tumor organoids-guided

adjuvant chemotherapy after surgical resection of
intrahepatic cholangiocarcinoma: A multicenter

and retrospective study

Shichao Zhang , Hao Shen 2,3† , Wenxin Wei , Lv Jin , Zhihao Xie , Jinhuan Liu , Wei Zhai , Zhilin Sha ,
1
1,2
1†
4
1†
5
2
Tao Yuan , Zhishi Yang , Yong Xia , Chen Liu , Jun Li , Timothy M Pawlik , Feng Shen * , and Kui Wang *
6
1,2
1,2
3
5
3
1
1,2
1 Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital and National Center for Liver Cancer, Naval Medical University,
Shanghai, China
2 Clinical Research Institute, Eastern Hepatobiliary Surgery Hospital and National Center for Liver Cancer, Naval Medical University,
Shanghai, China
3 Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
4 Department of Neurosurgery, The First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China
5 Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital and National Center for Liver Cancer, Naval Medical
University, Shanghai, China
6 Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
† These authors contributed equally to this work.
*Corresponding authors: Feng Shen (shenfengehbh@sina.com); Kui Wang (wangkuiykl@163.com)
Citation: Zhang S, Shen H, Wei W, Abstract
et al. Patient-derived tumor organoids-
guided adjuvant chemotherapy after
surgical resection of intrahepatic This multicenter retrospective study investigated the clinical utility of patient-
cholangiocarcinoma: A multicenter derived tumor organoids (PDOs) in guiding adjuvant chemotherapy for intrahepatic
and retrospective study. Organoid cholangiocarcinoma (ICC) patients. A total of 82 ICC patients at the Shanghai Eastern
Res. 2025;1(1): 8571.
doi: 10.36922/or.8571 Hepatobiliary Surgery Hospital and the Shanghai Tenth People’s Hospital between
2021 and 2022 were included in the study. All of these patients underwent surgical
Received: January 17, 2025 resection and were pathologically confirmed to have high-risk factors for recurrence.
Revised: February 25, 2025 Therefore, they received adjuvant chemotherapy post-surgery. Sixty-one PDOs
Accepted: March 7, 2025 were successfully established from resected tumor tissues and tested against four
common regimens: Gemcitabine + cisplatin, gemcitabine + oxaliplatin, capecitabine,
Published online: March 20, 2025 and S-1. A novel fluorescence-based method was developed for drug sensitivity
Copyright: © 2025 Author(s). testing, showing significant concordance with conventional half-maximal inhibitory
This is an Open-Access article concentration quantification. Patients were stratified into matched (n=26) and
distributed under the terms of the
Creative Commons Attribution unmatched (n=35) groups based on alignment between PDOs-based drug sensitivity
License, permitting distribution, and results and actual chemotherapy received. The matched group demonstrated
reproduction in any medium, which significantly improved recurrence-free survival (RFS) (hazard ratio = 2.52, p=0.007),
provided that the original work is
properly cited. with 63% versus 17% experiencing recurrence events. Through eXtreme Gradient
Boosting machine learning and Cox regression analyses, we identified PDOs-based
Publisher’s Note: AccScience
Publishing remains neutral with regard drug sensitivity, tumor multiplicity, and vascular invasion as key predictors of 2-year
to jurisdictional claims in published recurrence. A clinical nomogram incorporating these factors showed that patients
maps and institutional affiliations. with matched PDO-guided therapy had 46% 12-month RFS probability versus 28%
in unmatched cases. This study provides a clinically translatable platform to guide
adjuvant chemotherapy decisions and predict the prognosis of ICC patients with a
high recurrence risk after surgery.

Keywords: Intrahepatic cholangiocarcinoma; Patient-derived tumor organoids; Drug
sensitivity testing; Recurrence-free survival; Adjuvant therapy

Volume 1 Issue 1 (2025) 1 doi: 10.36922/or.8571