Dataset Information

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

ABSTRACT:

Background

Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis.

Methods

124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators.

Results

Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07-13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12-2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03-1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13-0.93, p = 0.036).

Conclusions

multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

SUBMITTER: Gruttadauria S

PROVIDER: S-EPMC7866287 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

Gruttadauria Salvatore S Barbera Floriana F Conaldi Pier Giulio PG Pagano Duilio D Liotta Rosa R Gringeri Enrico E Miraglia Roberto R Burgio Gaetano G Barbara Marco M Pietrosi Giada G Cammà Calogero C Di Francesco Fabrizio F

Cancers 20210129 3

<h4>Background</h4>Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to compleme ...[more]

PMID: 33572904

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Project description:ImportanceThe remnant liver after hepatectomy may have inadequate blood supply, especially following nonanatomical resection or vascular damage.ObjectiveTo evaluate whether remnant liver ischemia (RLI) may have an adverse effect on long-term survival and morbidity after liver resection in patients with hepatocellular carcinoma.Design, setting, and participantsThis study was a retrospective analysis at Seoul National University Bundang Hospital. Remnant liver ischemia was graded on postoperative computed tomographic scans in 328 patients who underwent hepatectomy for hepatocellular carcinoma between January 1, 2004, and December 31, 2013.Main outcomes and measuresRemnant liver ischemia was defined as reduced or absent contrast enhancement during the venous phase. Remnant liver ischemia was classified as minimal (none or marginal) or severe (partial, segmental, or necrotic).ResultsAmong 328 patients (252 male and 76 female; age range, 26-83 years [mean age, 58.2 years]), radiologic signs of severe RLI were found in 98 patients (29.9%), of whom 63, 16, and 19 had partial, segmental, or necrotic RLI, respectively. These patients experienced more complications and longer hospital stay than patients with minimal RLI. Preoperative history of transarterial embolization (odds ratio [OR], 1.77; 95% CI, 1.02-3.03; P = .04), use of the Pringle maneuver (OR, 1.96; 95% CI, 1.08-3.58; P = .03), and longer operative time (OR, 1.003; 95% CI, 1.002-1.005; P < .001) were independent risk factors for severe RLI. Early recurrence rates within 6 (60.2% vs 9.6%) or 12 (79.6% vs 18.7%) months after hepatectomy were higher in patients with severe RLI than in patients without RLI (P < .001). Severe remnant liver ischemia was an independent risk factor for overall survival (OR, 6.98; 95% CI, 4.27-11.43; P < .001) and disease-free survival (OR, 5.15; 95% CI, 3.62-7.35; P < .001).Conclusions and relevancePreventive management and technical refinements in hepatectomy are important to decrease the risk of RLI and to improve survival of patients with hepatocellular carcinoma.

Project description:Background and aimsCurrent prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection.MethodsConsecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery.ResultsA total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only.ConclusionThe GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.

Dataset Information

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

Background

Methods

Results

Conclusions

Publications

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

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