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17.06.2022 | Original Article

Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma

verfasst von: Junichi Shindoh, Yusuke Kawamura, Masahiro Kobayashi, Norio Akuta, Satoshi Okubo, Masaru Matsumura, Yoshiyuki Suzuki, Masaji Hashimoto

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 8/2022

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Abstract

Background

Increasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC.

Methods

The clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates.

Results

Multivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01–0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19–0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10–0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16–0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02–0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC.

Conclusions

Additional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.
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Literatur
1.
Zurück zum Zitat Arii S, Yamaoka Y, Futagawa S et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 2000; 32: 1224-1229.CrossRef Arii S, Yamaoka Y, Futagawa S et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 2000; 32: 1224-1229.CrossRef
2.
Zurück zum Zitat Takayama T, Makuuchi M, Hirohashi S et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 1998; 28: 1241-1246.CrossRef Takayama T, Makuuchi M, Hirohashi S et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 1998; 28: 1241-1246.CrossRef
3.
Zurück zum Zitat Livraghi T, Meloni F, Di Stasi M et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 2008; 47: 82-89.CrossRef Livraghi T, Meloni F, Di Stasi M et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 2008; 47: 82-89.CrossRef
4.
Zurück zum Zitat Shiina S, Tateishi R, Arano T et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 2012; 107: 569-577; quiz 578.CrossRef Shiina S, Tateishi R, Arano T et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 2012; 107: 569-577; quiz 578.CrossRef
5.
Zurück zum Zitat Clavien PA, Lesurtel M, Bossuyt PM et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13: e11-22.CrossRef Clavien PA, Lesurtel M, Bossuyt PM et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13: e11-22.CrossRef
6.
Zurück zum Zitat Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg 2004; 240: 451-459; discussion 459-461.CrossRef Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg 2004; 240: 451-459; discussion 459-461.CrossRef
7.
Zurück zum Zitat Zhu XD, Huang C, Shen YH et al. Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations. Liver Cancer 2021; 10: 320-329.CrossRef Zhu XD, Huang C, Shen YH et al. Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations. Liver Cancer 2021; 10: 320-329.CrossRef
8.
Zurück zum Zitat Matsuki R, Kawai K, Suzuki Y et al. Pathological Complete Response in Conversion Hepatectomy Induced by Lenvatinib for Advanced Hepatocellular Carcinoma. Liver Cancer 2020; 9: 358-360.CrossRef Matsuki R, Kawai K, Suzuki Y et al. Pathological Complete Response in Conversion Hepatectomy Induced by Lenvatinib for Advanced Hepatocellular Carcinoma. Liver Cancer 2020; 9: 358-360.CrossRef
9.
Zurück zum Zitat Ohya Y, Hayashida S, Tsuji A et al. Conversion hepatectomy for advanced hepatocellular carcinoma after right portal vein transection and lenvatinib therapy. Surg Case Rep 2020; 6: 318.CrossRef Ohya Y, Hayashida S, Tsuji A et al. Conversion hepatectomy for advanced hepatocellular carcinoma after right portal vein transection and lenvatinib therapy. Surg Case Rep 2020; 6: 318.CrossRef
10.
Zurück zum Zitat Sato N, Beppu T, Kinoshita K et al. Conversion Hepatectomy for Huge Hepatocellular Carcinoma With Arterioportal Shunt After Chemoembolization and Lenvatinib Therapy. Anticancer Res 2019; 39: 5695-5701.CrossRef Sato N, Beppu T, Kinoshita K et al. Conversion Hepatectomy for Huge Hepatocellular Carcinoma With Arterioportal Shunt After Chemoembolization and Lenvatinib Therapy. Anticancer Res 2019; 39: 5695-5701.CrossRef
11.
Zurück zum Zitat Tomonari T, Sato Y, Tanaka H et al. Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib: Three case reports. Medicine (Baltimore) 2020; 99: e22782.CrossRef Tomonari T, Sato Y, Tanaka H et al. Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib: Three case reports. Medicine (Baltimore) 2020; 99: e22782.CrossRef
12.
Zurück zum Zitat Wang Y, Lu LC, Guan Y et al. Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance. Exp Hematol Oncol 2021; 10: 45.CrossRef Wang Y, Lu LC, Guan Y et al. Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance. Exp Hematol Oncol 2021; 10: 45.CrossRef
13.
Zurück zum Zitat Shindoh J, Kawamura Y, Kobayashi Y et al. Prognostic Impact of Surgical Intervention After Lenvatinib Treatment for Advanced Hepatocellular Carcinoma. Ann Surg Oncol 2021. Shindoh J, Kawamura Y, Kobayashi Y et al. Prognostic Impact of Surgical Intervention After Lenvatinib Treatment for Advanced Hepatocellular Carcinoma. Ann Surg Oncol 2021.
14.
Zurück zum Zitat Salem R, Li D, Sommer N et al. Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial. Cancer Med 2021; 10: 5437-5447.CrossRef Salem R, Li D, Sommer N et al. Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial. Cancer Med 2021; 10: 5437-5447.CrossRef
15.
Zurück zum Zitat Kokudo N, Takemura N, Hasegawa K et al. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res 2019; 49: 1109-1113.CrossRef Kokudo N, Takemura N, Hasegawa K et al. Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC guidelines) 2019 update. Hepatol Res 2019; 49: 1109-1113.CrossRef
16.
Zurück zum Zitat National Cancer Institute, Division of Cancer Treated and Diagnosis. Cancer Therapy Evaluation Program. Adverse events/CTCAE. Available at: https: //ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#-ctc_40. Accessed December 23, 2018. National Cancer Institute, Division of Cancer Treated and Diagnosis. Cancer Therapy Evaluation Program. Adverse events/CTCAE. Available at: https: //ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#-ctc_40. Accessed December 23, 2018.
17.
Zurück zum Zitat Kawamura Y, Ikeda K, Hirakawa M et al. New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma. Hepatol Res 2010; 40: 1006-1014.CrossRef Kawamura Y, Ikeda K, Hirakawa M et al. New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma. Hepatol Res 2010; 40: 1006-1014.CrossRef
18.
Zurück zum Zitat Kawamura Y, Kobayashi M, Shindoh J et al. Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis. Liver Cancer 2020; 9: 275-292.CrossRef Kawamura Y, Kobayashi M, Shindoh J et al. Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis. Liver Cancer 2020; 9: 275-292.CrossRef
19.
Zurück zum Zitat Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010; 30: 52-60.CrossRef Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010; 30: 52-60.CrossRef
20.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390.CrossRef Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390.CrossRef
21.
Zurück zum Zitat Cheng AL, Kang YK, Chen Z et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34.CrossRef Cheng AL, Kang YK, Chen Z et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34.CrossRef
22.
Zurück zum Zitat Abou-Alfa GK, Meyer T, Cheng AL et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 2018; 379: 54-63.CrossRef Abou-Alfa GK, Meyer T, Cheng AL et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med 2018; 379: 54-63.CrossRef
23.
Zurück zum Zitat Bruix J, Qin S, Merle P et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389: 56-66.CrossRef Bruix J, Qin S, Merle P et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389: 56-66.CrossRef
24.
Zurück zum Zitat Finn RS, Qin S, Ikeda M et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382: 1894-1905.CrossRef Finn RS, Qin S, Ikeda M et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382: 1894-1905.CrossRef
25.
Zurück zum Zitat Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-1173.CrossRef Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391: 1163-1173.CrossRef
26.
Zurück zum Zitat Zhu AX, Kang YK, Yen CJ et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20: 282-296.CrossRef Zhu AX, Kang YK, Yen CJ et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20: 282-296.CrossRef
27.
Zurück zum Zitat Shindoh J, Kaseb A, Vauthey JN. Surgical strategy for liver cancers in the era of effective chemotherapy. Liver Cancer 2013; 2: 47-54.CrossRef Shindoh J, Kaseb A, Vauthey JN. Surgical strategy for liver cancers in the era of effective chemotherapy. Liver Cancer 2013; 2: 47-54.CrossRef
28.
Zurück zum Zitat Naganuma A, Suzuki Y, Hoshino T et al. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2021. Naganuma A, Suzuki Y, Hoshino T et al. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2021.
29.
Zurück zum Zitat Sugimoto R, Inada H, Tanaka Y et al. Improved indocyanine green retention after short-term lenvatinib withdrawal in three patients with hepatocellular carcinoma. Clin J Gastroenterol 2021; 14: 1484-1490.CrossRef Sugimoto R, Inada H, Tanaka Y et al. Improved indocyanine green retention after short-term lenvatinib withdrawal in three patients with hepatocellular carcinoma. Clin J Gastroenterol 2021; 14: 1484-1490.CrossRef
30.
Zurück zum Zitat Takahashi K, Kim J, Takahashi A et al. Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: A case report. World J Hepatol 2021; 13: 384-392.CrossRef Takahashi K, Kim J, Takahashi A et al. Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: A case report. World J Hepatol 2021; 13: 384-392.CrossRef
31.
Zurück zum Zitat Yano S, Kawaoka T, Johira Y et al. Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab. Medicine (Baltimore) 2021; 100: e27576.CrossRef Yano S, Kawaoka T, Johira Y et al. Advanced hepatocellular carcinoma with response to lenvatinib after atezolizumab plus bevacizumab. Medicine (Baltimore) 2021; 100: e27576.CrossRef
32.
Zurück zum Zitat Yokoo H, Takahashi H, Hagiwara M et al. Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report. World J Hepatol 2020; 12: 1349-1357.CrossRef Yokoo H, Takahashi H, Hagiwara M et al. Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report. World J Hepatol 2020; 12: 1349-1357.CrossRef
33.
Zurück zum Zitat 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: 7663-7672.CrossRef 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: 7663-7672.CrossRef
34.
Zurück zum Zitat Mise Y, Hasegawa K, Shindoh J et al. The Feasibility of Third or More Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma. Ann Surg 2015; 262: 347-357.CrossRef Mise Y, Hasegawa K, Shindoh J et al. The Feasibility of Third or More Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma. Ann Surg 2015; 262: 347-357.CrossRef
35.
Zurück zum Zitat Meniconi RL, Komatsu S, Perdigao F et al. Recurrent hepatocellular carcinoma: a Western strategy that emphasizes the impact of pathologic profile of the first resection. Surgery 2015; 157: 454-462.CrossRef Meniconi RL, Komatsu S, Perdigao F et al. Recurrent hepatocellular carcinoma: a Western strategy that emphasizes the impact of pathologic profile of the first resection. Surgery 2015; 157: 454-462.CrossRef
36.
Zurück zum Zitat Yang W, Chen MH, Wang MQ et al. Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment. Hepatol Res 2009; 39: 231-240.CrossRef Yang W, Chen MH, Wang MQ et al. Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment. Hepatol Res 2009; 39: 231-240.CrossRef
37.
Zurück zum Zitat Shindoh J, Kawamura Y, Kobayashi Y et al. Time-to-Interventional Failure as a New Surrogate Measure for Survival Outcomes after Resection of Hepatocellular Carcinoma. J Gastrointest Surg 2020; 24: 50-57.CrossRef Shindoh J, Kawamura Y, Kobayashi Y et al. Time-to-Interventional Failure as a New Surrogate Measure for Survival Outcomes after Resection of Hepatocellular Carcinoma. J Gastrointest Surg 2020; 24: 50-57.CrossRef
Metadaten
Titel
Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma
verfasst von
Junichi Shindoh
Yusuke Kawamura
Masahiro Kobayashi
Norio Akuta
Satoshi Okubo
Masaru Matsumura
Yoshiyuki Suzuki
Masaji Hashimoto
Publikationsdatum
17.06.2022
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Surgery / Ausgabe 8/2022
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-022-05388-9

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