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1. Introduction adjuvant chemotherapy between June 1, 2021, and June
1, 2022, at the Shanghai Eastern Hepatobiliary Surgery
Intrahepatic cholangiocarcinoma (ICC) is the second Hospital (EHBH) and the Shanghai Tenth People’s
most common primary liver cancer after hepatocellular Hospital (TJTP). Patients were divided into a matched
carcinoma, characterized by high aggressiveness and group and an unmatched group based on whether the
poor prognosis, with its incidence steadily increasing sensitive drugs identified by PDOs-based drug sensitivity
in recent decades, particularly in Southeast Asia and testing were consistent with the drugs used in actual
1
East Asia. Surgical resection is the primary treatment clinical treatment. The clinical treatment decisions were
for ICC; however, post-operative survival rates remain conducted independently from the cultivation and drug
unsatisfactory, with 5-year survival rates ranging from sensitivity testing of PDOs. The adjuvant chemotherapy
only 20% to 40%. Given the poor prognosis of surgically regimens decided by clinicians were not influenced by the
2-4
resected ICC, adjuvant chemotherapy has been commonly drug sensitivity results of PDOs. Therefore, this study is
implemented in clinical practice. For patients with high- observational in real world rather than interventional.
risk factors for recurrence, such as lymph node metastasis
or R1 resection, fluoropyrimidine- or gemcitabine-based This study received ethical approval from the Ethics
adjuvant chemotherapy regimens can significantly improve Committee of the Shanghai EHBH and the Shanghai Tenth
5
survival outcomes. Furthermore, a recent Japanese People’s Hospital (TJTP). All procedures involving human
multicenter randomized controlled trial demonstrated participants were carried out in accordance with the
that adjuvant S-1 can improve overall survival and Declaration of Helsinki, and written informed consent was
recurrence-free survival (RFS) in patients at high risk of obtained from each participant.
recurrence. However, even with adjuvant chemotherapy,
6
the 2-year recurrence rate remains as high as 40 – 75%. 2.2. Inclusion and exclusion criteria
The heterogeneity of ICC might be the key factor limiting The inclusion criteria applied in this study are as follows:
further improvements in therapeutic efficacy. Targeted (1) aged between 18 and 75 years; (2) histologically
therapies are currently the major form of approaches used confirmed ICC; (3) underwent liver resection; (4) presence
in precision medicine for ICC, but it remains unclear of high-risk factors for recurrence, including: (i) tumor
which patients would benefit from the recommended diameter >5 cm, (ii) multiple tumors, and (iii) pathological
chemotherapy regimens. A small cohort study suggested diagnosis indicating lymph node metastasis or R1 resection;
that specific genetic signatures might help identify patients and (5) received adjuvant chemotherapy. R1 resection is
who could benefit from chemotherapy, but these findings defined as a surgical margin status where microscopic
require further validation in larger cohorts. 7 residual tumor cells are present at the resection margin,
10
In recent years, the advent of tumor organoid technology indicating that the tumor has not been completely removed.
has opened new avenues for personalized cancer treatment. Patients with the following conditions were excluded from
Patient-derived tumor organoids (PDOs) can closely this study: (1) Received additional adjuvant treatments
mimic the biological characteristics and drug responses such as radiotherapy or targeted therapy combined with
of the original tumors. Emerging evidence demonstrates adjuvant chemotherapy; (2) diagnosed with other cancers;
8,9
that PDO models in gastric and colorectal cancers can (3) received other anticancer therapies before surgery; and
effectively mirror individual patients’ clinical responses to (4) failed to successfully establish PDOs.
chemotherapeutic regimens. 10-12 Furthermore, a landmark 2.3. Sample processing and PDOs culture
prospective study in breast cancer organoids has established
that therapy guided by these precision drug sensitivity Within 30 min of excision, the specimens were placed in an
profiles significantly enhances clinical outcomes. In this organoid-specific tissue preservation solution (A100L50,
13
retrospective study, we aim to evaluate the effectiveness Amoolo Biotech, China) and stored at 4°C for no more than
of adjuvant chemotherapy for ICC by utilizing tumor 10 h before processing. In brief, tumor tissues were washed
organoid-based drug sensitivity testing. Our objective is in Hank’s balanced salt solution (37150, STEMCELL
to provide a new approach for optimizing post-operative Technologies, Canada), cut into small pieces, and digested
treatment strategies and improving survival outcomes for in 5 mL of DMEM/F12 containing type II collagenase
ICC patients through organoid models. (Invitrogen, 17101015) at 37°C on a shaking incubator for
approximately 1 h. To remove red blood cells, the digested
2. Materials and methods tissue suspension was mixed with lysis buffer (FNN0021,
Invitrogen, USA) and centrifuged at ×300 g for 5 min. Tumor
2.1. Study design cells were collected, washed, counted, and resuspended
This study retrospectively enrolled ICC patients who in 20 μL of Matrigel (354237, Corning, USA), which was
underwent surgical resection and received post-operative then dropped into pre-warmed 60 mm culture dishes and

Volume 1 Issue 1 (2025) 2 doi: 10.36922/or.8571