Dataset Information

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma.

ABSTRACT:

Importance

Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival.

Objective

To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy.

Design, setting, and participants

This cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019.

Exposures

Chemotherapy alone and chemotherapy with liver-directed surgery or radiation.

Main outcomes and measures

Overall survival.

Results

A total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P?=?.048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P?=?.004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P?=?.045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P?Conclusions and relevanceIn this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study.

SUBMITTER: Sebastian NT

PROVIDER: S-EPMC6745054 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma.

Sebastian Nikhil T NT Tan Yubo Y Miller Eric D ED Williams Terence M TM Noonan Anne M AM Hays John L JL Abdel-Misih Sherif S Diaz Dayssy Alexandra DA

JAMA network open 20190904 9

<h4>Importance</h4>Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival.<h4>Objective</h4>To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy.<h4>Desi ...[more]

PMID: 31517963

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Project description:PurposeThe role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy.Patients and methodsIn this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort.ResultsFrom 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001).ConclusionIn patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Project description:BackgroundTreatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era.MethodsClinico-pathologic 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.ResultsAmong 362 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, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure.ConclusionSurvival 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. Cancer 2017;123:1354-1362. © 2016 American Cancer Society.

Project description:BackgroundThe effectiveness of adjuvant transarterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study was performed to identify ICC patients who would benefit from adjuvant TACE.Patients and methodsThe study included 553 patients who underwent hepatectomy for ICC between January 2008 and February 2011 at the Eastern Hepatobiliary Surgery Hospital and who were treated with or without TACE (122 with TACE and 431 without TACE). Survival risk stratification was performed using the established prognostic nomogram (ICC nomogram). The predictive performance was evaluated by concordance index and calibration. The tumor recurrence and overall survival (OS) rates were analyzed by the Kaplan-Meier method before and after propensity score matching (PSM).ResultsThe predictive performance of the ICC nomogram was demonstrated by the well-fitted calibration curves and an optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year recurrence and OS rates between the TACE and non-TACE groups were significantly different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1 PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs. 36.0%). By survival risk stratification based on ICC nomogram, only the patients in the lowest tertile (nomogram scores ?77) benefited from adjuvant TACE (TACE vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5-year OS).ConclusionAdjuvant TACE following liver resection might be suitable for ICC patients with high ICC nomogram scores (?77).Implications for practiceThe accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram, adjuvant transarterial chemoembolization following liver resection might be suitable only for ICC patients with high scores from the nomogram.

Dataset Information

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Publications

Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma.

Similar Datasets

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