Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection

Abstract

In this manuscript, we demonstrate that hepatic arterial infusion chemotherapy (HAIC) may provide comparable survival to resection for patients with liver-limited intrahepatic cholangiocarcinoma (IHC) and lymph node metastases (LNM). HAIC is an attractive form of liver-directed therapy and can be offered with lower morbidity and mortality risk than liver resection, while also providing adequate disease control for traditionally unresectable patients.Moreover, this manuscript bridges the translational connection between genomics and clinical care by analyzing the next generation sequencing (NGS) data for this cohort of patients, treated with both modalities. Patients with N1 disease and high-risk alterations, which included mutations in KRAS and TP53, and deletions in CDKN2A and CDKN2B, had significantly worse prognosis, regardless of treatment. Conversely, mutations in IDH1 and IDH2 as well as FGFR2 fusion events, had no association with survival. Our results support the routine use of NGS in all patients with IHC, which may provide valuable insights into which patients are unlikely to derive benefit from any form of liver-directed therapy Research.

Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

“…After assessment of the full text, nine studies were included. [23][24][25][26][27][28][29][30][31] The reasons for exclusion after full-text assessment were: no usage of HAIP with floxuridine for iCCA (n = 8), fewer than five iCCA patients (n = 4), no separate results reported for patients treated with HAIP chemotherapy (n = 2), no (median) overall survival reported (n = 2), and no outcomes reported for solely iCCA patients (n = 1) (Supplementary Table S2).…”

“…30 In seven studies, patients received concurrent systemic therapy and HAIP chemotherapy with floxuridine. [24][25][26][27][28][29]31 In the study by Jolissaint et al, 142 (72%) patients received concurrent systemic chemotherapy: 58 received gemcitabine/oxaliplatin, 41 received irinotecan, and 27 received gemcitabine alone. 28 In three studies, all patients received concurrent systemic chemotherapy; gemcitabine/cisplatin in the study by Pietge et al and gemcitabine/oxaliplatin in the study by Cercek et al 26,29 In the study by Konstantinidis et al, a variety of systemic regimens were used.…”

“…25,26,29 The rates of conversion to resection were reported in seven studies. [24][25][26][28][29][30][31] In the study by Jolissaint et al, including the patients from the three phase II trials, 14 out of 196 patients underwent a curative intent resection after HAIP chemotherapy. 28 In the study by Pietge et al, one patient underwent resection, achieving R1 resection status with eventual tumor progression 1 year postoperatively.…”

YY1 activates EMI2 and promotes the progression of cholangiocarcinoma through the PI3K/Akt signaling axis

“…Due to the increase in incidence, more and more researchers have focused their efforts on understanding cholangiocarcinoma (CCA). Based on the location, CCA is classified into different types [ 1 – 3 ].The pathogenesis of CCA is still unclear, and possible factors include hepatitis B, cholangiolithiasis, hepatic fascidiasis, chronic cholangitis, etc. Lymph node invasion is a key factor in poor prognosis of CCA [ 2 ].…”

“…Lymph node invasion is a key factor in poor prognosis of CCA [ 2 ]. Cholestasis and chronic cholangitis are recognized factors in the pathogenesis of CCA [ 3 ]. Chronic cholangitis can stimulate the secretion of cytokines and damage the DNA repair function, resulting in the formation of pro-cancer microenvironment, which involves the activation of multiple signaling pathways, such as PI3K/AKT signaling pathway [ 4 ].…”