Decision-Tree Models Indicative of Microvascular Invasion on MRI Predict Survival in Patients with Hepatocellular Carcinoma Following Tumor Ablation

Abstract

Purpose

Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE).

Patients and Methods

Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher’s exact and t-test, Kaplan–Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson’s correlation.

Results

OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed.

Conclusion

The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.

Keywords:

• cancer imaging
• hepatocellular carcinoma
• microvascular invasion
• magnetic resonance tomography
• predictive imaging biomarkers

Abbreviations

iBT, interstitial brachytherapy; cTACE, conventional transarterial chemoembolization; ALT, alanine aminotransferase; AST, aspartate aminotransferase; γ-GT, gamma-glutamyl transferase; AP, alkaline phosphatase; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; OS, overall survival; PFS, progression-free survival; TTP, time-to-progression; LTP, local tumor progression; IDR, intrahepatic distant recurrence, TCGA-LIHC, The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (public external database); art., arterial phase; pv., portal venous phase; ven., venous phase; HBP, hepatobiliary phase of T1-weighted images; DWI, diffusion weighted imaging; ADC, apparent diffusion coefficient maps.

Data Sharing Statement

Additional data are available to readers upon reasonable request to the corresponding author.

Ethical Approval

Institutional Review Board approval by the Charité – University Medicine Berlin’s human research committee was obtained.

Statistics and Biometry

No complex statistical methods were necessary for this paper.

Informed Consent

Informed consent was waived due to the retrospective study design.

Study Subjects or Cohorts Overlap

No study subjects or cohorts have been previously reported.

Acknowledgments

Parts of this work have been presented at the SIO Annual Meeting 2022, ECR Overture 2022, CIRSE 2022, and RSNA 2022, respectively. The authors like to thank Prof. Dr. Bernd Hamm for his guidance and supervision in- and outside the submitted work.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors state that this work has not received any funding. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Outside the submitted work, RS received a stipend from Berliner Krebsgesellschaft e.V.. CAH and LJS are currently fellows of the BIH Charité (Junior Digital) Clinician Scientist Program funded by the Charité-Universitätsmedizin Berlin and the Berlin Institute of Health. HX and YH are fellows of the Chinese Scholarship Council. LJS receives research grants from the Berliner Krebsgesellschaft e.V., the Collaborative Research Center (CRC) 1340 “Matrix in Vision” funded by the Deutsche Forschungsgemeinschaft (DFG), the DFG research unit 5628 “Multiscale MRE: in vivo physics of cancer”, and Guerbet, and honoraria and travel support from Guerbet. Outside the submitted work, BG reports honoraria and travel support in the last 10 years from Parexel/CALYX, C.R. BARD/BD, SIRTex Medical, St. Jude Medical, COOK, AngioDynamics, Pharmcept, Guerbet, Ewimed, Siemens, VARIAN, Terumo, Roche, Merck, 3M, Beacon Bioscience/ICON, IPSEN, Bayer, Pfizer, Eisai, MSD, and INARI; grants from INARI, Siemens, SIRTeX, BARD/BD. The authors report no other conflicts of interest in this work.