Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.

Trends in the use of adjuvant therapy for resected intrahepatic cholangiocarcinoma: getting ahead of the data

“…The increasing adoption of adjuvant chemotherapy noted in the study by Altman et al in the years 2000-2014 likely reflect clinician desire to do something Editorial Trends in the use of adjuvant therapy for resected intrahepatic cholangiocarcinoma: getting ahead of the data to improve patient outcomes even if only based on low quality evidence. Similar trends have been observed in the increasing use of neoadjuvant therapy for high-risk localized ICC despite the lack of level I evidence to support its efficacy (10). The global interest to identify a suitable adjuvant therapy for resected BTCs, even if the quality of evidence is not overwhelming, may also be evident in the quick incorporation of adjuvant capecitabine into national treatment guidelines despite a non-significant primary endpoint in the BILCAP trial, as well as other published negative adjuvant trials (11).…”

Primary tumor resection improves survival in patients with multifocal intrahepatic cholangiocarcinoma based on a population study

“…Meanwhile, Gaya et al found that compared with solitary ICCA, extended hepatectomy of multifocal ICCA was more frequent, but surgical resection of multiple lesions was still safe; there was no significant difference in the incidence of adverse events and perioperative mortality between the two groups 16 . Generally, in patients with normal liver function, the future liver remnant (FLR) > 20% is required, and in the case of impaired liver function, the more future liver remnant is required: the FLR of patients with fatty liver > 30%, the FLR of patients with liver cirrhosis > 40% 18 . Besides, in patients with insufficient residual liver volume, portal vein embolization (PVE) can make compensatory hyperplasia of the contralateral lobe in a short time and improve the possibility of R0 resection and the overall survival of the patients 19 .…”

The Role of Surgical Resection and Liver Transplantation for the Treatment of Intrahepatic Cholangiocarcinoma

“…Additional adjuncts in the neoadjuvant setting for iCCA include trans-arterial chemoembolization (TACE), drug-eluting bead chemoembolization, trans-arterial radioembolization (TARE), proton beam therapy (PBT), and hepatic artery infusion pumps [ 94 , 101 , 102 , 103 , 104 , 105 ]. While data on these therapies are mostly limited to advanced, metastatic iCCA, some reports have suggested successful downstaging of locally advanced disease, resulting in subsequent surgical resection.…”