Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients

Abstract

Purpose Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcomes remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era. Methods Clinicopathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group. Results Among 355 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies. In resection group, 3-year DSS rate was 58% for the early era and 67% for the late era (P=0.036), and 1-year IPFS was 50% for the early era and 75% for the late era (P=0.048). In radiation group, 3-year DSS was 12% for the early era and 37% for the late era (P=0.048), and 1-year IPFS was 48% for the early era and 64% for the late era (P=0.030). In chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy significantly more frequently developed liver failure at the time of death than patients treated with resection (P<0.001) or radiation (P<0.001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure. Conclusion Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure.

Wip1 is associated with tumorigenity and metastasis through MMP-2 in human intrahepatic cholangiocarcinoma

“…ICC is a fatal primary liver carcinoma, which originating from the intrahepatic bile duct epithelium beyond the second-order bile ducts [ 5 ] [ 26 , 27 ]. ICC is the second most common all primary liver cancers in the worldwide, the actual incidence has been increasing steadily and substantially over the past decades and has a poor outcomes and high mortality rate due to the high invasiveness and recurrence [ 1 , 28 – 30 ]. Some previous studies reported that Wip1 expression was associated with miR-17-5p through activation of the p38 pathway in hepatocellular carcinoma (HCC)[ 31 ].…”

Management of unresectable intrahepatic cholangiocarcinoma: how do we decide among the various liver-directed treatments?

“…A n o t a b l e f e a t u r e o f u n r e s e c t a b l e i n t r a h e p a t i c cholangiocarcinoma is that the majority of patients die of tumor-related liver failure (2); while extrahepatic distant metastasis is prevalent, it is not as frequently the cause of death as the intrahepatic disease. Inadequate control of the primary tumor and satellite lesions can lead to parenchymal loss and liver failure due to vascular compromise (portal venous or hepatic vein obstruction) or biliary obstruction (potentially leading to sepsis) (3). Our review of patients with unresectable intrahepatic cholangiocarcinoma who received radiotherapy at MD Anderson Cancer Center from 2002 to 2014 revealed that a bioequivalent dose less than 80.5 Gy BED led to poor tumor control.…”

“…In this study, we noted improvements over time with resection and radiotherapy, likely owing to technical improvements in these treatments. On multivariable analysis, receipt of local therapy (with resection or definitive radiotherapy) was the sole predictor of death without liver failure (3).…”

Non-surgical management of patients with intrahepatic cholangiocarcinoma in the United States, 2004–2015: an NCDB analysis

“…With technological advances in radiation oncology and ablation technologies, alternative methods are increasingly utilized for local tumor control. This rationale for liverdirected therapies is underscored by data that show survival benefit and decreased risk of liver failure in patients who receive local therapy with resection or definitive radiotherapy (6). To that end, multiple modalities have been heterogeneously employed for local tumor control.…”