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Published in: Clinical Journal of Gastroenterology 3/2023

07-02-2023 | Hepatocellular Carcinoma | Case Report

Two cases of hepatocellular carcinoma successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment

Authors: Satoshi Takakusagi, Hinako Tanaka, Atsushi Naganuma, Satoru Kakizaki, Kei Shibuya, Tatsuya Ohno, Hitoshi Takagi, Toshio Uraoka

Published in: Clinical Journal of Gastroenterology | Issue 3/2023

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Abstract

We herein report two cases of huge hepatocellular carcinoma (HCC) that were successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment. Case 1, an 84-year-old man, was diagnosed with HCC (maximum diameter: 11 cm) with portal invasion and presented HCC rupture. After obtaining hemostasis with transcatheter embolization, three cycles of atezolizumab-bevacizumab therapy were administered, and marked shrinkage of the HCC was confirmed. However, he developed jaundice, liver damage and cerebral subcortical hemorrhage. Thus, atezolizumab-bevacizumab therapy was discontinued. Total bilirubin, transaminase levels, and physical activity improved well with prednisolone, an antihypertensive agent, and rehabilitation. Thus, treatment with carbon ion radiotherapy (CIRT) was added, and the treatment effect at 4 months after CIRT was judged as a complete response (CR) according to the modified response evaluation criteria in solid tumors (mRECIST). Case 2, a 68-year-old man, was diagnosed with HCC (maximum diameter: 14 cm). Hepatic resection was difficult because the residual liver volume after treatment would be insufficient. Five cycles of atezolizumab-bevacizumab therapy were performed, and marked shrinkage of the HCC to a maximum diameter of 9 cm was confirmed. The treatment was converted to CIRT, and atezolizumab-bevacizumab therapy resumed one month after CIRT. The treatment effect at 3 months after CIRT was judged as CR according to mRECIST. Although conversion therapy after atezolizumab-bevacizumab therapy, including surgery and radiofrequency ablation, have been reported, CIRT may be a promising new tool for conversion therapy for HCC.
Literature
1.
go back to reference Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–80.CrossRefPubMed Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–80.CrossRefPubMed
2.
go back to reference Ikai I, Arii S, Okazaki M, et al. Report of the 17th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2007;37:676–91.CrossRefPubMed Ikai I, Arii S, Okazaki M, et al. Report of the 17th nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res. 2007;37:676–91.CrossRefPubMed
3.
go back to reference Mulcahy MF. Management of hepatocellular cancer. Curr Opin Oncol. 2005;6:423–35. Mulcahy MF. Management of hepatocellular cancer. Curr Opin Oncol. 2005;6:423–35.
4.
go back to reference Kuvshinoff BW, Ota DM. Radiofrequency ablation of liver tumors: influence of technique and tumor size. Surgery. 2002;132:605–11.CrossRefPubMed Kuvshinoff BW, Ota DM. Radiofrequency ablation of liver tumors: influence of technique and tumor size. Surgery. 2002;132:605–11.CrossRefPubMed
5.
go back to reference Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122–30.CrossRefPubMed Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122–30.CrossRefPubMed
6.
go back to reference European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69: 182–236. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69: 182–236.
7.
go back to reference Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.CrossRefPubMed Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905.CrossRefPubMed
8.
go back to reference Kudo M. A novel treatment strategy for patients with intermediate-stage HCC who are not suitable for TACE: Upfront systemic therapy followed by curative conversion. Liver Cancer. 2021;10:539–44.CrossRefPubMedPubMedCentral Kudo M. A novel treatment strategy for patients with intermediate-stage HCC who are not suitable for TACE: Upfront systemic therapy followed by curative conversion. Liver Cancer. 2021;10:539–44.CrossRefPubMedPubMedCentral
9.
go back to reference Apisarnthanarax S, Bowen SR, Combs SE. Proton beam therapy and carbon ion radiotherapy for hepatocellular carcinoma. Semin Radiat Oncol. 2018;28:309–20.CrossRefPubMed Apisarnthanarax S, Bowen SR, Combs SE. Proton beam therapy and carbon ion radiotherapy for hepatocellular carcinoma. Semin Radiat Oncol. 2018;28:309–20.CrossRefPubMed
10.
go back to reference Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76:681–93.CrossRefPubMed Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76:681–93.CrossRefPubMed
11.
go back to reference Shindoh J, Kawamura Y, Kobayashi Y, et al. Prognostic impact of surgical intervention after lenvatinib treatment for advanced hepatocellular carcinoma. Ann Surg Oncol. 2021;28:7663–72.CrossRefPubMed Shindoh J, Kawamura Y, Kobayashi Y, et al. Prognostic impact of surgical intervention after lenvatinib treatment for advanced hepatocellular carcinoma. Ann Surg Oncol. 2021;28:7663–72.CrossRefPubMed
12.
go back to reference Hoshino T, Naganuma A, Furusawa A, et al. A case of conversion hepatectomy for huge hepatocellular carcinoma with adrenal metastasis and vascular invasion after atezolizumab-bevacizumab treatment. Clin J Gastroenterol. 2022;15:776–83.CrossRefPubMed Hoshino T, Naganuma A, Furusawa A, et al. A case of conversion hepatectomy for huge hepatocellular carcinoma with adrenal metastasis and vascular invasion after atezolizumab-bevacizumab treatment. Clin J Gastroenterol. 2022;15:776–83.CrossRefPubMed
13.
14.
go back to reference Shiba S, Shibuya K, Okamoto M, et al. Clinical impact of hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma. Radiat Oncol. 2020;15:195.CrossRefPubMedPubMedCentral Shiba S, Shibuya K, Okamoto M, et al. Clinical impact of hypofractionated carbon ion radiotherapy on locally advanced hepatocellular carcinoma. Radiat Oncol. 2020;15:195.CrossRefPubMedPubMedCentral
15.
go back to reference Hack SP, Spahn J, Chen M, et al. IMbrave 050: a phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020;16:975–89.CrossRefPubMed Hack SP, Spahn J, Chen M, et al. IMbrave 050: a phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020;16:975–89.CrossRefPubMed
16.
go back to reference Shibuya K, Katoh H, Koyama Y, et al. Efficacy and safety of 4 fractions of carbon-ion radiation therapy for hepatocellular carcinoma: a prospective study. Liver Cancer. 2021;11:61–74.CrossRefPubMedPubMedCentral Shibuya K, Katoh H, Koyama Y, et al. Efficacy and safety of 4 fractions of carbon-ion radiation therapy for hepatocellular carcinoma: a prospective study. Liver Cancer. 2021;11:61–74.CrossRefPubMedPubMedCentral
17.
go back to reference Lim KC, Chow PK, Allen JC, et al. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the milan criteria. Br J Surg. 2012;99:1622–9.CrossRefPubMed Lim KC, Chow PK, Allen JC, et al. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the milan criteria. Br J Surg. 2012;99:1622–9.CrossRefPubMed
18.
19.
go back to reference Ohmatsu K, Hashimoto Y, Kawanishi M, et al. Abscopal complete regression of hepatocellular carcinoma with multiple pleural metastases. Int Cancer Conf J. 2020;10:54–8.CrossRefPubMedPubMedCentral Ohmatsu K, Hashimoto Y, Kawanishi M, et al. Abscopal complete regression of hepatocellular carcinoma with multiple pleural metastases. Int Cancer Conf J. 2020;10:54–8.CrossRefPubMedPubMedCentral
20.
go back to reference Nakanishi M, Chuma M, Hige S, et al. Abscopal effect on hepatocellular carcinoma. Am J Gastroenterol. 2008;103:1320–1.CrossRefPubMed Nakanishi M, Chuma M, Hige S, et al. Abscopal effect on hepatocellular carcinoma. Am J Gastroenterol. 2008;103:1320–1.CrossRefPubMed
21.
go back to reference Helm A, Ebner DK, Tinganelli W, et al. Combining heavy-ion therapy with immunotherapy: an update onrecent developments. Int J Part Ther. 2018;5:84–93.CrossRefPubMedPubMedCentral Helm A, Ebner DK, Tinganelli W, et al. Combining heavy-ion therapy with immunotherapy: an update onrecent developments. Int J Part Ther. 2018;5:84–93.CrossRefPubMedPubMedCentral
22.
go back to reference Helm A, Tinganelli W, Simoniello P, et al. Reduction of lung metastases in a mouse osteosarcoma model treated with carbon ions and immune checkpoint inhibitors. Int J Radiat Oncol Biol Phys. 2021;109:594–602.CrossRefPubMed Helm A, Tinganelli W, Simoniello P, et al. Reduction of lung metastases in a mouse osteosarcoma model treated with carbon ions and immune checkpoint inhibitors. Int J Radiat Oncol Biol Phys. 2021;109:594–602.CrossRefPubMed
23.
go back to reference Zhang H, Huang Z, Zou X, Liu T. Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. 2016;7:82473–81.CrossRefPubMedPubMedCentral Zhang H, Huang Z, Zou X, Liu T. Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. 2016;7:82473–81.CrossRefPubMedPubMedCentral
24.
go back to reference Aussilhou B, Dokmak S, Faivre S, et al. J. Preoperative liver hypertrophy induced by portal flow occlusion before major hepatic resection for colorectal metastases can be impaired by bevacizumab. Ann Surg Oncol. 2009;16(6):1553–9.CrossRefPubMed Aussilhou B, Dokmak S, Faivre S, et al. J. Preoperative liver hypertrophy induced by portal flow occlusion before major hepatic resection for colorectal metastases can be impaired by bevacizumab. Ann Surg Oncol. 2009;16(6):1553–9.CrossRefPubMed
25.
go back to reference Lu JF, Bruno R, Eppler S, et al. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008;62:779–86.CrossRefPubMed Lu JF, Bruno R, Eppler S, et al. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008;62:779–86.CrossRefPubMed
26.
go back to reference Yoshida M, Ogino H, Iwata H, et al. Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma. Oncol Lett. 2019;17:3026–34.PubMedPubMedCentral Yoshida M, Ogino H, Iwata H, et al. Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma. Oncol Lett. 2019;17:3026–34.PubMedPubMedCentral
27.
go back to reference Yu R, Tan Z, Xiang X, et al. Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data. BMC Cancer. 2017;17:608.CrossRefPubMedPubMedCentral Yu R, Tan Z, Xiang X, et al. Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data. BMC Cancer. 2017;17:608.CrossRefPubMedPubMedCentral
28.
go back to reference Sorin Y, Ikeda K, Kawamura Y, et al. Effectiveness of particle radiotherapy in various stages of hepatocellular carcinoma: a pilot study. Liver Cancer. 2018;7:323–34.CrossRefPubMedPubMedCentral Sorin Y, Ikeda K, Kawamura Y, et al. Effectiveness of particle radiotherapy in various stages of hepatocellular carcinoma: a pilot study. Liver Cancer. 2018;7:323–34.CrossRefPubMedPubMedCentral
Metadata
Title
Two cases of hepatocellular carcinoma successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment
Authors
Satoshi Takakusagi
Hinako Tanaka
Atsushi Naganuma
Satoru Kakizaki
Kei Shibuya
Tatsuya Ohno
Hitoshi Takagi
Toshio Uraoka
Publication date
07-02-2023
Publisher
Springer Nature Singapore
Published in
Clinical Journal of Gastroenterology / Issue 3/2023
Print ISSN: 1865-7257
Electronic ISSN: 1865-7265
DOI
https://doi.org/10.1007/s12328-023-01768-z

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