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. 2025 Apr 9;17(8):1275.
doi: 10.3390/cancers17081275.

Comparing the Prognostic Value of Quantitative Response Assessment Tools and LIRADS Treatment Response Algorithm in Patients with Hepatocellular Carcinoma Following Interstitial High-Dose-Rate Brachytherapy and Conventional Transarterial Chemoembolization

Robin Schmidt  1   2 , Christopher Rueger  1 , Han Xu  1 , Yubei He  1   2 , Emine Yaren Yilmaz  1   2 , Luisa Heidemann  1   2 , Ornela Sulejmani  1   2 , Yu Liu  1   2 , Lasse Noack  1 , Friederike Hesse  1   3 , Richard Ruppel  1 , Sara A Abosabie  1 , Charlie Alexander Hamm  1   3 , Tobias Penzkofer  1 , Bernhard Gebauer  1 , Lynn Jeanette Savic  1   2   3
Affiliations

Comparing the Prognostic Value of Quantitative Response Assessment Tools and LIRADS Treatment Response Algorithm in Patients with Hepatocellular Carcinoma Following Interstitial High-Dose-Rate Brachytherapy and Conventional Transarterial Chemoembolization

Robin Schmidt et al. Cancers (Basel). .

Abstract

Background/Objectives: The aim of this study was to investigate the prognostic value of established response assessment tools for hepatocellular carcinoma (HCC) treated with high-dose-rate interstitial brachytherapy (iBT) alone or with transarterial chemoembolization (cTACE). Methods: (Non-)responders were categorized using size-based RECIST 1.1 and WHO criteria, enhancement-based mRECIST and EASL criteria, and the LI-RADS Treatment Response Algorithm (LR-TRA). The outcomes were the overall survival (OS), progression-free survival (PFS), and time to progression (TTP). The statistics used included Fisher's exact test, a t-test, the Mann-Whitney-U test, and a Kaplan-Meier analysis. The median OS, PFS, and TTP were higher in patients following iBT (26.3, 9.1, and 13.0 months) than following cTACE/iBT (23.3, 7.6, and 9.2 months). Results: The enhancement-based criteria identified more responders and predicted PFS and TTP better compared to the size-based criteria. At two months, the cTACE/iBT responders showed improved PFS (mRECIST and EASL: 11.3 vs. 2.3 and 11.0 vs. 2.3, p < 0.01) and TTP (mRECIST and EASL: 11.9 vs. 2.4 months, p < 0.01) by the enhancement-based criteria. An EASL assessment at five months predicted improved survival following both cTACE/iBT (PFS: 11.9 vs. 5.1 months, p = 0.03; TTP: 12.4 vs. 5.0, p < 0.01) and iBT (11.1 vs. 5.1 months, p = 0.04; 13.0 vs. 5.3, p < 0.01). The LR-TRA showed OS benefits at five months for cTACE/iBT responders. Size-based criteria were not prognostic. Conclusions: Extending follow-up post-iBT or post-iBT/cTACE may improve responder stratification and prognostication.

Keywords: LIRADS Treatment Response Algorithm; hepatocellular carcinoma; interstitial brachytherapy; locoregional therapies; response assessment; transarterial chemoembolization.

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Conflict of interest statement

The authors do not declare any conflicts of interest. Outside the submitted work, L.J.S. received funding from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG): CRC 1340 “Matrix in vision”—Project-ID 372486779; research unit FOR5628 “Onco-MRE”. L.J.S. received research grants from the Berliner Krebsgesellschaft e.V., Charité 3R, and research grants and honoraria from Guerbet. F.H., C.A.H. and L.J.S. are fellows of the BIH (Junior Digital) Clinician Scientist Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health. Y.H. received stipends from the Chinese Scholar Council. E.Y.Y. received a stipend from the Fuldt Stiftung. T.P. receives funding from Berlin Institute of Health (Advanced Clinician Scientist Grant, Platform Grant), Ministry of Education and Research (BMBF, 01KX2021 (RACOON), 01KX2121 (XNUM 2.0′, RACOON), 68GX21001A, 01ZZ2315D), German Research Foundation (DFG, SFB 1340/2), European Union (H2020, CHAIMELEON: 952172, DIGITAL, EUCAIM: 101100633) and reports research agreements (no personal payments, outside of submitted work) with AGO, Aprea AB, ARCAGY-GINECO, Astellas Pharma Global Inc. (APGD), Astra Zeneca, Clovis Oncology, Inc., Holaira, Incyte Corporation, Karyopharm, Lion Biotechnologies, Inc., MedImmune, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals, Inc., Morphotec Inc., NovoCure Ltd., PharmaMar S.A. and PharmaMar USA, Inc., Roche, Siemens Healthineers, and TESARO Inc., and fees for a book translation (Elsevier B.V.). B.G. receives payment for lectures from Parexel/Calyx, C. R. Bard/BD, Sirtex Medical, St. Jude Medical, Cook, AngioDynamics, Pharmcept, Guerbet, Ewimed, Boston Scientific, Terumo, Roche,Merck, 3M, Beacon Bioscience/ICON, Ipsen, Bayer, Pfizer, Eisai, MSD, Inari, and Siemens/Varian.

Figures

Figure 1
Figure 1
Waterfall plots illustrating the relative tumoral change within completed treatment cycles according to the respective response criteria of RECIST, WHO, mRECIST, and EASL at two and five months of follow-up for (A) patients following interstitial brachytherapy (iBT) and (B) following conventional transarterial chemoembolization (cTACE)/iBT. Response categories include complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Figure 2
Figure 2
Donut plots illustrate the distribution of tumor response according to the response categories of LIRADS Treatment Response Algorithm (LR-TRA) v2018 and v2024 radiation core at two and five months of follow-up for (A) patients following interstitial brachytherapy (iBT) and (B) following conventional transarterial chemoembolization (cTACE)/iBT.
Figure 3
Figure 3
Survival measures in patients following interstitial brachytherapy (iBT) alone. Green lines indicate responders vs. non-responders (red lines) according to the respective response criteria at five months of follow-up. Significant results were found for RECIST, mRECIST, and EASL and are highlighted next to grayed-out boxes. Survival times are reported in Supplementary Table S1.
Figure 4
Figure 4
Survival measures in patients following conventional transarterial chemoembolization (cTACE) prior to interstitial brachytherapy (iBT). Green lines indicate responders vs. non-responders (red lines) according to the respective response criteria at five months of follow-up. Significant results were found for mRECIST, EASL, and both LI-TRA criteria and are highlighted next to grayed-out boxes. Survival times are reported in Supplementary Table S2.
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