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Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection.

ABSTRACT: Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate.For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; PDFS = 0.055, POS = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (PDFS = 0.439, POS = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (PDFS = 0.042, POS = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS.For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI.

SUBMITTER: Chen JL

PROVIDER: S-EPMC4748913 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection.

Chen Jian-Lin JL Lao Xiang-Ming XM Lin Xiao-Jun XJ Xu Li L Cui Bo-Kang BK Wang Jun J Lin Guo-He GH Shuang Ze-Yu ZY Mao Yi-Ze YZ Huang Xin X Yun Jing-Ping JP Jin Jie-Tian JT Li Sheng-Ping SP

Medicine 20160201 5

Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. ...[more]

PMID: 26844496

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Project description:BackgroundThe optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI.MethodsIn this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1-2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events.ResultsBetween June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3-48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99-29.14) vs. 9.27 months (95% CI 6.05-13.70), hazard ratio [HR] = 0.70 (95% CI 0.52-0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99-62.58) vs. 22.37 months (95% CI 10.84-33.91), HR = 0.68 (95% CI 0.48-0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.ConclusionHepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

Project description:PurposePrognostic prediction after curative resection of primary hepatocellular carcinoma (PHCC) remains an arduous task. The S-index calculated from γ-glutamyl transpeptidase, albumin, and platelets is reported to predict the severity of liver fibrosis. We constructed a nomogram for predicting the survival probability of PHCC based on a new indicator, the S-index, combined with other routine clinical parameters.Patients and methodsWe selected 490 patients with PHCC postradical surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2007 and January 2014. The subjects were randomly allocated into the training cohort and the validation cohort in the ratio 7:3 by the digital method. Important variables screened by univariate analysis were included in multivariate analysis to obtain independent risk factors for predicting the prognosis of PHCC. The construction of the nomogram was based on Cox proportional hazard regression models. The concordance index (C-index) was used in the nomogram for evaluating the model performance for prognosis. We drew time-dependent receiver operating characteristic curves to compare our model with other staging systems.ResultsThe nomogram based on six independent risk factors after multivariate analyses had good predictive power after radical surgery of PHCC. In the training and validation groups, the C-index of the nomogram was highly consistent for evaluating survival from PHCC. Compared with the traditional scoring system, the areas under time-dependent receiver operating characteristic curves were 0.7382, 0.7293, and 0.7520 for 1-, 3-, and 5-year overall survival, respectively. In summary, the nomogram showed excellent results in terms of prognosis of PHCC.ConclusionBased on the S-index and the other clinical indicators, we developed a precise nomogram that predicts the survival probability of patients with PHCC after radical surgery. This tool can provide effective information for surgeons and patients.

Project description:BackgroundThe prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.MethodsIn this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.ResultsA total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769-4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545-1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686-6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06).ConclusionsThe present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.

Project description:Background & aimsThe effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC.MethodsUsing a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS.ResultsAmong the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC.ConclusionThis real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

Project description:BackgroundFor Chinese patients with hepatocellular carcinoma (HCC), surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.MethodsA multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, γ-glutamyltransferase, α-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell's concordance index (C-index) was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.ResultsShanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients), and in the three independent validation cohorts, the CI s for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α). The identified subset of patients at low risk could be ideal candidates for curative surgery, and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery. Finally, a web server with individualized outcome prediction and treatment recommendation was constructed.ConclusionsBased on the largest cohort up to date, we established Shanghai Score - an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery. The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.

Dataset Information

Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection.

Publications

Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection.

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