Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma

Abstract

IMPORTANCE Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. OBJECTIVE To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. MAIN OUTCOMES AND MEASURESOverall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. RESULTS A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median [IQR] age, 62 [53-70] years; 79 [56.0%] women) and 178 in the resection group (median [IQR] age, 60 [50-69] years; 91 [51.1%] men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% [n = 124] vs 34.3% [n = 61]), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7%[94] vs 24.2% [43]). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07).CONCLUSIONS AND RELEVANCE This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.

Treatment for Patients With Multifocal Intrahepatic Cholangiocarcinoma

“…To the Editor We read the study by Franssen et al with great interest. The authors showed that the overall survival after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy in patients with multifocal intrahepatic cholangiocarcinoma was comparable with that in patients who underwent resection and confirmed the results of a previous study .…”

Laparoscopic or open liver resection for intrahepatic cholangiocarcinoma: A meta-analysis and systematic review

“…In addition, several guidelines also recommend palliative chemotherapy for bi-or multifocal ICC (39,40). However, a recent cohort study reported similar long-term efficacy of surgical resection and chemotherapy for multifocal ICC, and a metaanalysis suggested that re-operation may partly improve the short-term and long-term outcomes of patients with recurrent ICC (41,42). At present, open hepatectomy is the most common surgical method used for the treatment of ICC.…”

A cellular senescence-related classifier based on a tumorigenesis- and immune infiltration-guided strategy can predict prognosis, immunotherapy response, and candidate drugs in hepatocellular carcinoma

“…Consequently, elimination of accumulated detrimental senescence and induction of acute cellular senescence might be an important direction, and more studies on the interaction between cellular senescence and antitumor microenvironment are warranted. Noticeably, the remaining three compounds have also been reported to have antitumor capability, although their correlation with cellular senescence has not been characterized (77)(78)(79). In consideration of the complicated involved pathways in cellular senescence (4,(52)(53)(54)(55), we permuted additional candidate compounds, including cell-cycle inhibitors, bromodomain and BET inhibitors, PI3K-AKT pathway inhibitors, and multikinase inhibitors, and the TIS-high group exhibited a higher susceptibility to these drugs.…”