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

SIMPLE SUMMARY: The first core tip of this study is that we summarized the experience of conversion therapy of intrahepatic cholangiocarcinoma (IHCC) in a single center and found conversion therapy could provide a significant improvement in the overall survival of patients with IHCC. Previous studies mainly focused on case reports and case series, and our research provided more evidence for the efficacy of conversion therapy in IHCC. The second is that we established the organoid of IHCC for drug screening and firstly verified the results of drug screening tests in cancer organoid were consistent with the levels of efficacy observed in the patient from whom it was derived. Cancer organoid is a promising technology for conversion therapy according to our study but more organoids are still needed. 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.