Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid

Abstract

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

Establishment and drug screening of patient-derived extrahepatic biliary tract carcinoma organoids

“…Ganesh et al also reported that cancer PDO of rectal cancer can predict the sensitivity of original cancer to both chemotherapy and radiotherapy [ 15 ]. Recently, our team has successfully established PDOs of intrahepatic cholangiocarcinoma (iCCA) and evaluated its drug sensitivity, which was consistent with the observed clinical effects [ 16 ]. However, very few studies have established PDO from eBTC to date.…”

Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping

“…Although tumor origin, carcinogenesis, and response to chemotherapy are expected to differ between the two types, in-depth studies of these differences have proven experimentally problematic owing to the absence of applicable ex vivo subtype models and difficulties in acquiring sufficient tumor tissue for analysis. Therefore, a truly representative model of cholangiocarcinoma subtypes is needed for studying differences in development, carcinogenesis, and anticancer drug responsiveness between types.Recently developed organoid culture techniques enable the formation of adult stem cell-derived cancer organoids from cholangiocarcinoma specimens [15][16][17][18][19][20] . Importantly, the resulting organoids show similar phenotypic and genetic characteristics compared with the original primary tumor.…”

Conversion therapy for advanced intrahepatic cholangiocarcinoma with lenvatinib and pembrolizumab combined with gemcitabine plus cisplatin: A case report and literature review

“…( 51 ) reported that 22% of patients with advanced ICC receiving radioembolization plus chemotherapy could be downstaged to surgical intervention, of which 8 patients survived after 24 months of follow-up. By means of systemic or regional therapy, adequate tumor downstaging was accomplished, and patients could obtain a generally favorable prognosis ( 52 – 54 ). Le Roy B. et al.…”