Correspondence to letter to the editor on “Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis”

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Clin Mol Hepatol. 2025;31(1):e93-e95
Publication date (electronic) : 2024 November 6
doi : https://doi.org/10.3350/cmh.2024.0943
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
Corresponding author : Yoon Jun Kim Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2228, Fax: +82-2-743-6701, E-mail: yoonjun@snu.ac.kr
Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea
Received 2024 October 25; Accepted 2024 November 1.

Dear Editor,

We appreciate Dr. Li and colleagues for their insightful comments on our recent study [1], which compared the outcomes of transarterial radioembolization (TARE) and tyrosine kinase inhibitors (TKIs) in patients with treatment-naïve hepatocellular carcinoma (HCC) and segmental or lobar portal vein tumor thrombosis (PVTT) [2]. We agree with Dr. Li’s comments on future directions based on this research and would like to further expand the discussion.

First, we agree with the opinion that the high cost of TARE may limit the expansion of its use. Although TARE may be advantageous in older patients and larger HCC with similar or superior efficacy and significantly fewer post-procedural complications, including post-embolization syndrome, compared to conventional transarterial chemoembolization (TACE), its use is limited in many countries due to cost [3,4]. The high cost may serve as a barrier to the expansion of TARE indications, particularly in low-income countries where the prevalence of liver cancer remains high. However, a recent study from Japan suggests that TARE may be more cost-effective than TACE under certain conditions. This study compared TARE and TACE with drug-eluting beads (DEB-TACE) using a Markov model [5]. The authors showed that TARE would be more cost-effective than DEB-TACE if the reimbursement price for radioactive microspheres was set about 2.8% lower than in the United Kingdom. Although different reimbursement policies across the countries make it difficult to generalize the results, these findings may result from the fact that TACE is more likely to require repeated treatments, whereas TARE often ends with a single treatment of the target lesion. In addition, TARE may be more cost-effective not only compared to TACE, but also compared to systemic treatment. Systemic treatment must be continued until disease progression or other severe side effects are identified. As novel systemic agents for advanced HCC, including immune checkpoint inhibitors, are more expensive than TKIs, TARE still serves as a good treatment option.

Second, it should be noted that regimens such as atezoli-zumab–bevacizumab and tremelimumab–durvalumab are becoming established as first-line systemic treatments for the treatment of advanced HCC.6 Both atezolizumab–bevacizumab and tremelimumab–durvalumab have shown significant survival benefits compared to sorafenib [7,8], and it is worth comparing the efficacy of these agents with TARE in patients with HCC and PVTT. Our group is collecting data to compare the effectiveness of atezolizumab–bevacizumab and TARE in another retrospective multicenter study and may present the results soon. Future randomized controlled trials comparing the two groups would provide more reliable results. Although tremelimumab–durvalumab was introduced later than atezolizumab–bevacizumab, it may be beneficial for patients who cannot use bevacizumab because of the high risk of bleeding. In particular, patients with Vp4 PVTT may consider using tremelimumab–durvalumab due to the increased risk of variceal bleeding with atezolizumab–bevacizumab [9], and it will be interesting to compare tremelimumab–durvalumab with TARE in this population.

Lastly, as Dr. Li suggests, it is important not only to compare TARE with other systemic therapies, but also to consider combinations of the two. In a study comparing the efficacy of TARE alone and TARE plus sorafenib, there was no difference in survival and objective response rate between the two groups [10]. Although propensity score matching was performed, the study was limited by small retrospective data. Recently, a single-arm phase I/IIa study showed promising results with the combination of TARE and durvalumab [11]. When durvalumab was administered every 4 weeks after TARE, the median time to progression was 15.2 months and 29.2% of patients achieved a complete response, resulting in an objective response rate of 83.3%. There were no treatment-emergent serious adverse events, suggesting that there was no apparent evidence of synergistic toxicity of the TARE and durvalumab combination. Therefore, it is expected that the combination of an immune checkpoint inhibitor with TARE may achieve higher efficacy without increasing complications by selecting the appropriate patient population and delivering a sufficient dose of radiation.

Once again, we deeply appreciate the thoughtful comments from Dr. Li and colleagues. As the role of TARE and novel systemic agents in the treatment of advanced HCC becomes increasingly important, we look forward to further pivotal studies comparing or combining TARE and systemic treatments, including immune checkpoint inhibitors.

Notes

Authors’ contribution

MH Hur and YJ Kim both drafted and reviewed the correspondence equally.

Conflicts of Interest

Moon Haeng Hur: Nothing to declare; Yoon Jun Kim: Yoon Jun Kim receives research grants from BTG, Boston Scientific, AstraZeneca, Gilead Sciences, Samjin, BL&H, and Bayer, and lecture fees from Roche, Abbvie, Eisai, Boston Scientific, BMS, BTG, Bayer, MSD, Novo Nordisk, Green Cross Cell, Boehringer Ingelheim, and Gilead Sciences.

Acknowledgements

This work was supported by the Korean Association for Study of the Liver (KASL)-Korean Liver Foundation (KLF) Research Fund in 2021 and Sirtex Technology PTY LTD. Sirtex provided grant funding to the Korea Radioembolization Association. Sirtex had no role in the study design, recruitment of patients, procedures, data collection, analysis or interpretation of the findings.

Abbreviations

HCC

hepatocellular carcinoma

DEB

drug-eluting beads

PVTT

portal vein tumor thrombosis

TACE

transarterial chemoembolization

TARE

transarterial radioembolization

TKI

tyrosine kinase inhibitor

References

1. Li H, Lu H, Shen XP, Li XS. Comparison of the therapeutic effects of transarterial radioembolization and tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2025;31:e3–e4.
2. Hur MH, Cho Y, Kim DY, Lee JS, Kim GM, Kim HC, et al. Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol 2023;29:763–778.
3. Cho Y, Choi JW, Kwon H, Kim KY, Lee BC, Chu HH, et al. Transarterial chemoembolization for hepatocellular carcinoma: 2023 expert consensus-based practical recommendations of the Korean Liver Cancer Association. Clin Mol Hepatol 2023;29:521–541.
4. Cho Y, Kim BH, Park JW. Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: an Asian perspective comparison. Clin Mol Hepatol 2023;29:252–262.
5. Shirota G, Sato S, Yasunaga H, Aso S, Akahane M, Itoh D, et al. Transarterial radioembolization vs transarterial chemoembolization with drug-eluting beads for treating hepatocellular carcinoma: a cost-effectiveness analysis in Japanese healthcare system. Jpn J Radiol 2024;42:1501–1515.
6. Sankar K, Gong J, Osipov A, Miles SA, Kosari K, Nissen NN, et al. Recent advances in the management of hepatocellular carcinoma. Clin Mol Hepatol 2024;30:1–15.
7. Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid 2022;1:EVIDoa2100070.
8. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:1894–1905.
9. Ha Y, Kim JH, Cheon J, Jeon GS, Kim C, Chon HJ. Risk of variceal bleeding in patients with advanced hepatocellular carcinoma receiving atezolizumab/bevacizumab. Clin Gastroenterol Hepatol 2023;21:2421–2423. e2.
10. Facciorusso A, Bargellini I, Cela M, Cincione I, Sacco R. Comparison between Y90 radioembolization plus sorafenib and Y90 radioembolization alone in the treatment of hepatocellular carcinoma: a propensity score analysis. Cancers (Basel) 2020;12:897.
11. Lee YB, Nam JY, Cho EJ, Lee JH, Yu SJ, Kim HC, et al. A phase I/IIa trial of yttrium-90 radioembolization in combination with durvalumab for locally advanced unresectable hepatocellular carcinoma. Clin Cancer Res 2023;29:3650–3658.

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