Combined transarterial chemoembolization and stereotactic body radiation therapy as a bridge therapy to liver transplant for hepatocellular carcinoma

Abstract

Liver transplant (LT) is the curative treatment for patients with hepatocellular carcinoma (HCC). Bridge therapies are local treatments given to patients on the LT waitlist, to prevent tumor progression and to reduce the dropout rate. Case presentation: We reported a 40-year-old man diagnosed with Barcenola-Clinic Liver Cancer BCLC intermediate stage HCC and Child-Pugh A5 hepatitis B virus cirrhosis who underwent combined bridge therapies to LT. Firstly, the patient received transarterial chemoembolization (TACE) for two times and showed a partial response. Then he underwent stereotactic body radiation therapy (SBRT) with a total dose of 45 Gy in 3 fractions. Three months later, the tumor size and serum protein induced by Vitamin K absence or antagonists-II, alpha fetoprotein levels decreased gradually. In June 2019 a suitable donor was found and his LT was successfully performed. Conclusion: We propose that a combination of TACE and SBRT was feasible as bridge therapy for HCC patients on the LT waitlist.

Keywords

Transarterial chemoembolization / stereotactic body radiation therapy / bridge therapy / hepatocellular carcinoma / liver transplant

References

[1] IARC. Cancer Today. Available from: http://gco.iarc.fr/today/. [Last accessed on 24 Jul 2020]

[2] Coletta M,Benedetti Cacciaguerra A,Rossi R.Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same?.Transl Gastroenterol Hepatol2017;2:78 PMCID:PMC5639014

[3] Cescon M,Ravaioli M.Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate..J Hepatol2013;58:609-18

[4] Washburn K,Harper A.Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system..Am J Transplant2010;10:1643-8

[5] Yao FY,Nikolai B,Kerlan R.Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list..Liver Transpl2002;8:873-83

[6] Yao FY,Nikolai B,Davern TJ.A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy..Liver Transpl2003;9:684-92

[7] Millonig G,Freund MC,Stadlmann S.Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma..Liver Transpl2007;13:272-9

[8] Otto G,Heise M,Mönch C.Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma..Liver Transpl2006;12:1260-7

[9] De Luna W,Ahmed A,Ayoub W.Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation..Am J Transplant2009;9:1158-68

[10] Katz AW,Qu Z,Milano MT.Stereotactic hypofractionated radiation therapy as a bridge to transplantation for hepatocellular carcinoma: clinical outcome and pathologic correlation..Int J Radiat Oncol Biol Phys2012;83:895-900

[11] O’Connor JK,Davis GL,Klintmalm GB.Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation..Liver Transpl2012;18:949-54

[12] Sapisochin G,Doherty M,Goldaracena N.Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis..J Hepatol2017;67:92-9

[13] Paik EK,Jang WI,Cho CK.Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma..Radiat Oncol2016;11:22 PMCID:PMC4759954

[14] Honda Y,Aikata H,Fukuhara T.Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma..J Gastroenterol Hepatol2013;28:530-6

[15] Cho JY,Park HC,Sohn W.The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma..Liver Int2014;34:795-801

[16] Kudo M,Ueshima K,Shiina S.Response evaluation criteria in cancer of the liver version 5 (RECICL 2019 revised version)..Hepatol Res2019;49:981-9

[17] Benedict SH,Followill D,Hinson W.Stereotactic body radiation therapy: the report of AAPM Task Group 101..Med Phys2010;37:4078-101

[18] Allard MA,Ruiz A,Paule B.Does pathological response after transarterial chemoembolization for hepatocellular carcinoma in cirrhotic patients with cirrhosis predict outcome after liver resection or transplantation?.J Hepatol2015;63:83-92

[19] Decaens T,Bresson-Hadni S,Gugenheim J.Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma..Liver Transpl2005;11:767-75

[20] She WH.Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation..Transl Gastroenterol Hepatol2016;1:34 PMCID:PMC5244605

[21] Choi SH.Stereotactic body radiotherapy: does it have a role in management of hepatocellular carcinoma?.Yonsei Med J2018;59:912-22 PMCID:PMC6127430

[22] Blomgren H,Näslund I.Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients..Acta Oncol1995;34:861-70

[23] Kollmann D,Selzner M.Bridging to liver transplantation in HCC patients..Langenbecks Arch Surg2017;402:863-71

[24] Sandroussi C,Lee M,Fischer S.Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma..Transpl Int2010;23:299-306

[25] Eriguchi T,Sanuki N,Aoki Y.Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system..Int J Radiat Oncol Biol Phys2013;85:1006-11

[26] Moore A,Tobar A,Benjaminov O.Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma..Radiat Oncol2017;12:163 PMCID:PMC5649060

[27] Gresswell S,Hasan S,Machado L.Stereotactic body radiotherapy used as a bridge to liver transplant in patients with hepatocellular carcinoma and Child-Pugh score ≥8 cirrhosis..J Radiosurg SBRT.2018;5:261-7 PMCID:PMC6255717

[28] Belghiti J,Greig PD,Poon RT.Treatment before liver transplantation for HCC..Ann Surg Oncol2008;15:993-1000

[29] European Association For The Study Of The Liver. European Organisation For Research And Treatment Of CancerEASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma..J Hepatol2012;56:908-43

[30] Golfieri R,Cucchetti A,Carpenzano M.Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas..Hepatology2011;53:1580-9

[31] ClinicalTrials.gov. Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) as Bridge to Liver Transplant (SBRTvsTACE). Available from: https://clinicaltrials.gov/ct2/show/NCT02182687. [Last accessed on 24 Jul 2020]

[32] ClinicalTrials.gov. Stereotactic Body Radiation Therapy (SBRT) vs Trans-Arterial Chemoembolization (TACE) as Bridge to Transplant (SBRTvsTACE). Available from: https://clinicaltrials.gov/ct2/show/NCT03960008. [Last accessed on 24 Jul 2020]

[33] Jacob R,Redden DT,Aal AK.Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥ 3 cm..HPB (Oxford)2015;17:140-9 PMCID:PMC4299388

[34] Buckstein M,Facciuto M,Taouli B.Phase II trial using combination of TACE and SBRT for unresectable single large HCC: interim report..Int J Radiat Oncol Biol Phys2019;105:E214-5

[35] Price TR,Sandrasegaran K,Maluccio MA.Evaluation of response after stereotactic body radiotherapy for hepatocellular carcinoma..Cancer2012;118:3191-8

[36] Sanuki-Fujimoto N,Ohashi T,Iwabuchi S.CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function..Br J Radiol2010;83:1063-71 PMCID:PMC3473607