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Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

ABSTRACT: BACKGROUND AND AIMS:The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT. METHODS:Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non-AT groups based on whether AT was administered or not. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems. RESULTS:A total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non-AT group (43.0 months vs 21.0 months, P = .015; 16.0 months vs 11.0 months, P = .045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P = .023; P = .046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only "middle-risk" patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P = .033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P = .039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P = .007). CONCLUSION:With the current data, we conclude that AT benefits ICC patients following radical resection, especially those "middle-risk" patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation.

SUBMITTER: Wang L

PROVIDER: S-EPMC7163087 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

Wang Lei L Deng Manjun M Ke Qiao Q Lou Jianying J Zheng Shuguo S Bi Xinyu X Wang Jianming J Guo Wei W Li Fuyu F Wang Jian J Zheng Yamin Y Li Jingdong J Cheng Shi S Zhou Weiping W Zeng Yongyi Y

Cancer medicine 20200219 8

<h4>Background and aims</h4>The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT.<h4>Methods</h4>Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 ...[more]

PMID: 32072774

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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.

Project description:Presentation of the Case A 37-year-old woman presented at 35 weeks of gestation with her third child with failure to adequately gain weight and was noted by her obstetrician to have delay in the growth of her baby. Ultrasound of the abdomen incidentally revealed the presence of a liver lesion. After additional evaluation, she ultimately delivered her daughter at 36 weeks uneventfully. She subsequently underwent additional evaluation. Liver magnetic resonance imaging (MRI) revealed a 5-cm solitary solid mass in segment 4A of the liver, concerning for malignancy. Serum α-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)19-9, CA15-3, and CA125 were all normal. Liver biopsy was positive for adenocarcinoma. The tumor cells demonstrated a phenotype suggesting a possible breast primary, although the immunohistochemistry did not support that diagnosis and the tumor was negative for mammaglobin, gross cystic disease fluid protein (GCDFP)-15, estrogen receptor (ER), and progesterone receptor (PR) (Table 1). The tumor was also CDX2 and cardiotrophin-1 negative, but cytokeratin (CK) 19 positive. Her endoscopic retrograde cholangiopancreatography, upper endoscopy, colonoscopy, breast mammogram, and breast MRI were completely normal. A positron emission tomography-computed tomography scan showed a fluorodeoxyglucose-avid 5.8-cm × 6.0-cm hypoattenuating lesion with peripheral enhancement involving segment 4 and segment 8 at the dome. In addition, central necrosis within the lesion was noted. The left main portal vein was mildly attenuated by the mass. She eventually underwent a left hepatectomy en bloc with caudate resection, portal lymphadenectomy, cholecystectomy, and omental pedicle flap. On exploration of the abdomen, no additional disease was noted. The final pathology revealed a 9.4-cm moderately to poorly differentiated adenocarcinoma of the intrahepatic bile ducts. Venous invasion was present. Perineural invasion was absent. The margins were negative. Thirteen lymph nodes were obtained, all of which were negative, consistent with a stage T2, N0, MX intrahepatic cholangiocarcinoma. The tumor was positive for CK7, CK19, and CA19-9 and negative for CK20, CDX2, CA125, ER, PR, GCDFP-15, synaptophysin, and chromogranin (Table 1). The uninvolved liver was unremarkable and a trichrome stain showed no fibrosis. Following an uneventful postoperative recovery, she was referred for consideration of adjuvant therapy.

Project description:BACKGROUD:Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection. PATIENTS AND METHODS:PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS:22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76). CONCLUSION:With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed.

Project description:BackgroundLiver resection is the most effective treatment for intrahepatic cholangiocarcinoma. Recurrent disease is frequent; however, recurrence patterns are ill-defined and prognostic models are lacking.Study designA primary cohort of 189 patients who underwent resection for intrahepatic cholangiocarcinoma was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease-free survival identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie intrahepatic cholangiocarcinoma study group).ResultsRecurrence within 24 months most often involved the liver (82.7%), and most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for disease-free survival were tumor size and multifocality (based on imaging); tumor size, multifocality, vascular invasion, and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low-risk and high-risk groups for recurrence. In the validation cohort (n = 522), high-risk patients had a greater likelihood of recurrence (hazard ratio = 2.17; 95% CI, 1.74-2.72; p < 0.001). The postoperative model included tumor size, vascular invasion, and positive nodal disease on pathology and classified patients in low-, intermediate-, and high-risk groups in the primary cohort. As compared with low-risk patients in the validation cohort, intermediate- and high-risk patients were more likely to experience recurrence (hazard ratio = 1.9; 95% CI, 1.41-2.47; p < 0.001 and hazard ratio = 2.99; 95% CI, 2.08-4.31; p < 0.001, respectively).ConclusionsRecurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which can guide treatment recommendations.

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Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

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Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study.

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