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Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma.

ABSTRACT: BACKGROUND & AIMS:Microvascular invasion (MVI) is a critical prognostic factor for operable hepatocellular carcinoma (HCC). This study aimed to explore the performance of circulating tumour DNA (ctDNA) in evaluating MVI status preoperatively. METHODS:Seventy-three HCC patients were enrolled and randomly divided into a training cohort and a validation cohort in a 2:1 ratio, and preoperative blood and surgical tissue samples were obtained. Genomic alterations were analysed using targeted deep sequencing with a 1021-gene panel. RESULTS:In training cohort, 260 somatic mutations were identified in 40 blood samples (81.6%). CtDNA mutation was verified in paired tissue sample in 39 patients (97.5%). In univariate analysis, ctDNA allele frequency (AF) and largest tumour diameter were associated with the presence of MVI, but ctDNA AF was the only independent risk factor in multivariate analysis. With the cut-off value of 0.83%, ctDNA AF determined the presence of MVI with the sensitivity of 89.7% and specificity of 80.0% in the training cohort, and the sensitivity of 78.6% and the specificity of 81.8% in the validation cohort. In preoperative evaluation, ctDNA AF, AFP level and BCLC staging were associated with recurrence-free survival in both univariate and multivariate analysis. CONCLUSIONS:CtDNA can serve as an independent risk factor of MVI for operable HCC and help determining precise treatment strategies. The integration of ctDNA in the management of operable HCC may achieve better clinical outcomes.

SUBMITTER: Wang D

PROVIDER: S-EPMC7496978 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma.

Wang Dong D Xu Yaping Y Goldstein Jennifer B JB Ye Ke K Hu Xi X Xiao Liang L Li Lifeng L Chang Lianpeng L Guan Yanfang Y Long Guo G He Qiongzhi Q Yi Xin X Zhang Jianjun J Wang Zhiming Z Xia Xuefeng X Zhou Ledu L

Liver international : official journal of the International Association for the Study of the Liver 20200523 8

<h4>Background & aims</h4>Microvascular invasion (MVI) is a critical prognostic factor for operable hepatocellular carcinoma (HCC). This study aimed to explore the performance of circulating tumour DNA (ctDNA) in evaluating MVI status preoperatively.<h4>Methods</h4>Seventy-three HCC patients were enrolled and randomly divided into a training cohort and a validation cohort in a 2:1 ratio, and preoperative blood and surgical tissue samples were obtained. Genomic alterations were analysed using tar ...[more]

PMID: 32279416

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Project description:BackgroundMicrovascular invasion (MVI) is an independent risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). To perform a meta-analysis to investigate the diagnostic performance of radiomics for the preoperative evaluation of MVI in HCC and the effect of potential factors.Materials and methodsA systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies focusing on the preoperative evaluation of MVI in HCC with radiomics methods. Data extraction and quality assessment of the retrieved studies were performed. Statistical analysis included data pooling, heterogeneity testing and forest plot construction. Meta-regression and subgroup analyses were performed to reveal the effect of potential explanatory factors [design, combination of clinical factors, imaging modality, number of participants, and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) applicability risk] on the diagnostic performance.ResultsTwenty-two studies with 4,129 patients focusing on radiomics for the preoperative prediction of MVI in HCC were included. The pooled sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were 84% (95% CI: 81, 87), 83% (95% CI: 78, 87) and 0.90 (95% CI: 0.87, 0.92). Substantial heterogeneity was observed among the studies (I²=94%, 95% CI: 88, 99). Meta-regression showed that all investigative covariates contributed to the heterogeneity in the sensitivity analysis (P < 0.05). Combined clinical factors, MRI, CT and number of participants contributed to the heterogeneity in the specificity analysis (P < 0.05). Subgroup analysis showed that the pooled sensitivity, specificity and AUC estimates were similar among studies with CT or MRI.ConclusionRadiomics is a promising noninvasive method that has high preoperative diagnostic performance for MVI status. Radiomics based on CT and MRI had a comparable predictive performance for MVI in HCC. Prospective, large-scale and multicenter studies with radiomics methods will improve the diagnostic power for MVI in the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259363, identifier CRD42021259363.

Project description:BackgroundRadiomics has emerged as a new approach that can help identify imaging information associated with tumor pathophysiology. We developed and validated a radiomics nomogram for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC).MethodsTwo hundred and eight patients with pathologically confirmed HCC (training cohort: n = 146; validation cohort: n = 62) who underwent preoperative gadoxetic acid-enhanced magnetic resonance (MR) imaging were included. Least absolute shrinkage and selection operator logistic regression was applied to select features and construct signatures derived from MR images. Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and radiomics signatures associated with MVI, which were then incorporated into the predictive nomogram. The performance of the radiomics nomogram was evaluated by its calibration, discrimination, and clinical utility.ResultsHigher α-fetoprotein level (p = 0.046), nonsmooth tumor margin (p = 0.003), arterial peritumoral enhancement (p < 0.001), and the radiomics signatures of hepatobiliary phase (HBP) T1-weighted images (p < 0.001) and HBP T1 maps (p < 0.001) were independent risk factors of MVI. The predictive model that incorporated the clinicoradiological factors and the radiomic features derived from HBP images outperformed the combination of clinicoradiological factors in the training cohort (area under the curves [AUCs] 0.943 vs. 0.850; p = 0.002), though the validation did not have a statistical significance (AUCs 0.861 vs. 0.759; p = 0.111). The nomogram based on the model exhibited C-index of 0.936 (95% CI 0.895-0.976) and 0.864 (95% CI 0.761-0.967) in the training and validation cohort, fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram.ConclusionsThe nomogram incorporating clinicoradiological risk factors and radiomic features derived from HBP images achieved satisfactory preoperative prediction of the individualized risk of MVI in patients with HCC.

Dataset Information

Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma.

Publications

Preoperative evaluation of microvascular invasion with circulating tumour DNA in operable hepatocellular carcinoma.

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