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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Hepatocellular Carcinoma | Study protocol

Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial

Authors: Liang-Cheng Chen, Wen-Yen Chiou, Hon-Yi Lin, Moon-Sing Lee, Yuan-Chen Lo, Li-Wen Huang, Chun-Ming Chang, Tsung-Hsing Hung, Chih-Wen Lin, Kuo-Chih Tseng, Dai-Wei Liu, Feng-Chun Hsu, Shih-Kai Hung

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Hepatocellular carcinoma (HCC) accounts for 75–85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking.
Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE.

Methods

The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor.

Discussion

SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent.

Trial registration

Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139) on Sep. 29, 2016. This study is ongoing.
Literature
1.
Global Burden of Disease Cancer C, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R et al: The global burden of Cancer 2013. JAMA Oncol, 2015, 1(4):505–527.
2.
3.
Chang IC, Huang SF, Chen PJ, Chen CL, Chen CL, Wu CC, Tsai CC, Lee PH, Chen MF, Lee CM, et al. The hepatitis viral status in patients with hepatocellular carcinoma: a study of 3843 patients from Taiwan liver Cancer network. Medicine. 2016;95(15):e3284.PubMedPubMedCentralCrossRef
4.
Chiang CJ, Lo WC, Yang YW, You SL, Chen CJ, Lai MS. Incidence and survival of adult cancer patients in Taiwan, 2002–2012. Journal of the Formosan Medical Association = Taiwan yi zhi. 2016.
5.
6.
7.
McMasters KM, Vauthey JN. Hepatocellular carcinoma: targeted therapy and multidisciplinary care. New York: Springer; 2011.CrossRef
8.
Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg. 2003;197(5):753–8.PubMedCrossRef
9.
Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. The Cochrane database of systematic reviews. 2011;3:CD004787.
10.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.PubMedCrossRef
11.
Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B, Rapaccini GL, Gasbarrini G. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian Centre. Gut. 2005;54(3):411–8.PubMedPubMedCentralCrossRef
12.
Matsuo Y, Yoshida K, Nishimura H, Ejima Y, Miyawaki D, Uezono H, Ishihara T, Mayahara H, Fukumoto T, Ku Y, et al. Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy. J Radiat Res. 2016;57(5):512–23.PubMedPubMedCentralCrossRef
13.
Yoon K, Kwak J, Cho B, Park JH, Yoon SM, Lee SW, Kim JH. Gated Volumetric-Modulated Arc Therapy vs. Tumor-Tracking CyberKnife Radiotherapy as Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Dosimetric Comparison Study Focused on the Impact of Respiratory Motion Managements. PLoS One. 2016;11(11) e0166927.
14.
Su TS, Liang P, Liang J, Lu HZ, Jiang HY, Cheng T, Huang Y, Tang Y, Deng X. Long-term survival analysis of stereotactic ablative radiotherapy versus liver resection for small hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2017;98(3):639–46.PubMedCrossRef
15.
Seo YS, Kim MS, Yoo HJ, Jang WI, Paik EK, Han CJ, Lee BH. Radiofrequency ablation versus stereotactic body radiotherapy for small hepatocellular carcinoma: a Markov model-based analysis. Cancer Med. 2016;5(11):3094–101.PubMedPubMedCentralCrossRef
16.
Kimura T, Aikata H, Takahashi S, Takahashi I, Nishibuchi I, Doi Y, Kenjo M, Murakami Y, Honda Y, Kakizawa H, et al. Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies. Hepatol Res. 2015;45(4):378–86.PubMedCrossRef
17.
Jung J, Yoon SM, Han S, Shim JH, Kim KM, Lim YS, Lee HC, Kim SY, Park JH, Kim JH. Alpha-fetoprotein normalization as a prognostic surrogate in small hepatocellular carcinoma after stereotactic body radiotherapy: a propensity score matching analysis. BMC Cancer. 2015;15:987.PubMedPubMedCentralCrossRef
18.
Takeda A, Sanuki N, Eriguchi T, Kobayashi T, Iwabutchi S, Matsunaga K, Mizuno T, Yashiro K, Nisimura S, Kunieda E. Stereotactic ablative body radiotherapy for previously untreated solitary hepatocellular carcinoma. J Gastroenterol Hepatol. 2014;29(2):372–9.PubMedCrossRef
19.
Sanuki N, Takeda A, Oku Y, Mizuno T, Aoki Y, Eriguchi T, Iwabuchi S, Kunieda E. Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol. 2014;53(3):399–404.PubMedCrossRef
20.
Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, Imajo K, Aoki Y, Saito H, Kunieda E. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer. 2016;122(13):2041–9.PubMedCrossRef
21.
Kim JW, Seong J, Lee IJ, Woo JY, Han KH. Phase I dose escalation study of helical intensity-modulated radiotherapy-based stereotactic body radiotherapy for hepatocellular carcinoma. Oncotarget. 2016;7(26):40756–66.PubMedPubMedCentral
22.
Guarneri A, Franco P, Trino E, Campion D, Faletti R, Mirabella S, Gaia S, Ragona R, Diotallevi M, Saracco G, et al. Stereotactic ablative radiotherapy in the treatment of hepatocellular carcinoma >3 cm. Med Oncol. 2016;33(10):104.PubMedCrossRef
23.
Lo CH, Yang JF, Liu MY, Jen YM, Lin CS, Chao HL, Huang WY. Survival and prognostic factors for patients with advanced hepatocellular carcinoma after stereotactic ablative radiotherapy. PLoS One. 2017;12(5):e0177793.PubMedPubMedCentralCrossRef
24.
Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, Schipper MJ, Feng M. Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J Clin Oncol. 2016;34(5):452–9.PubMedCrossRef
25.
Palma DA, Haasbeek CJ, Rodrigues GB, Dahele M, Lock M, Yaremko B, Olson R, Liu M, Panarotto J, Griffioen GH, et al. Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET): study protocol for a randomized phase II trial. BMC Cancer. 2012;12:305.PubMedPubMedCentralCrossRef
26.
Jacob R, Turley F, Redden DT, Saddekni S, Aal AK, Keene K, Yang E, Zarzour J, Bolus D, Smith JK, et al. Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of >/= 3 cm. HPB (Oxford). 2015;17(2):140–9.CrossRef
27.
Paik EK, Kim MS, Jang WI, Seo YS, Cho CK, Yoo HJ, Han CJ, Park SC, Kim SB, Kim YH. Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma. Radiat Oncol. 2016;11:22.PubMedPubMedCentralCrossRef
28.
Lo CH, Huang WY, Lee MS, Lin KT, Lin TP, Chang PY, Fan CY, Jen YM. Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization. Eur J Gastroenterol Hepatol. 2014;26(3):345–52.PubMedCrossRef
29.
Yang JF, Lo CH, Huang WY. Is stereotactic body radiotherapy better than radiofrequency ablation for the treatment of hepatocellular carcinoma? J Clin Oncol. 2016;34(23):2797.PubMedPubMedCentralCrossRef
30.
De Bari B, Ozsahin M, Bize P, Boussaha T, Deplanque G, Wagner D, Bourhis J, Denys A. Can stereotactic body radiotherapy really be considered the preferred treatment in large hepatocellular carcinoma? J Clin Oncol. 2016;34(23):2798–9.PubMedPubMedCentralCrossRef
31.
Kwon JH, Bae SH, Kim JY, Choi BO, Jang HS, Jang JW, Choi JY, Yoon SK, Chung KW. Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer. BMC Cancer. 2010;10:475.PubMedPubMedCentralCrossRef
32.
Meng M, Wang H, Zeng X, Zhao L, Yuan Z, Wang P, Hao X. Stereotactic body radiation therapy: a novel treatment modality for inoperable hepatocellular carcinoma. Drug Discov Ther. 2015;9(5):372–9.PubMedCrossRef
33.
Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK, Dinniwell RE, Kassam Z, Ringash J, Cummings B, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31(13):1631–9.PubMedCrossRef
34.
Huertas A, Baumann AS, Saunier-Kubs F, Salleron J, Oldrini G, Croise-Laurent V, Barraud H, Ayav A, Bronowicki JP, Peiffert D. Stereotactic body radiation therapy as an ablative treatment for inoperable hepatocellular carcinoma. Radiother Oncol. 2015;115(2):211–6.PubMedCrossRef
35.
Jang WI, Kim MS, Bae SH, Cho CK, Yoo HJ, Seo YS, Kang JK, Kim SY, Lee DH, Han CJ, et al. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiat Oncol. 2013;8:250.PubMedPubMedCentralCrossRef
36.
Teraoka Y, Kimura T, Aikata H, Daijo K, Osawa M, Honda F, Nakamura Y, Morio K, Morio R, Hatooka M, et al. Clinical outcomes of stereotactic body radiotherapy for elderly patients with hepatocellular carcinoma. Hepatol Res. 2017.
37.
Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, Tibballs J, Meyer T, Patch DW, Burroughs AK. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 2007;30(1):6–25.PubMedCrossRef
38.
Veltri A, Moretto P, Doriguzzi A, Pagano E, Carrara G, Gandini G. Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC). Eur Radiol. 2006;16(3):661–9.PubMedCrossRef
39.
Guo W, He X, Li Z, Li Y. Combination of Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) vs. surgical resection (SR) on survival outcome of early hepatocellular carcinoma: a meta-analysis. Hepatogastroenterology. 2015;62(139):710–4.PubMed
40.
Choi BO, Choi IB, Jang HS, Kang YN, Jang JS, Bae SH, Yoon SK, Chai GY, Kang KM. Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer. 2008;8:351.PubMedPubMedCentralCrossRef
41.
Honda Y, Kimura T, Aikata H, Nakahara T, Naeshiro N, Tanaka M, Miyaki D, Nagaoki Y, Kawaoka T, Takaki S, et al. Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. Hepatogastroenterology. 2014;61(129):31–6.PubMed
42.
Honda Y, Kimura T, Aikata H, Kobayashi T, Fukuhara T, Masaki K, Nakahara T, Naeshiro N, Ono A, Miyaki D, et al. Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28(3):530–6.PubMedCrossRef
43.
Janoray G, Mornex F. follow-up after stereotactic body radiation therapy for liver tumours: a review of the literature and recommendations. Cancer Radiother. 2015;19(6–7):573–81.PubMedCrossRef
44.
Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH, Bae SH, Jung da H, Kim KB, Lee DH, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118(21):5424–31.PubMedCrossRef
45.
Seo YS, Kim MS, Yoo SY, Cho CK, Choi CW, Kim JH, Han CJ, Park SC, Lee BH, Kim YH, et al. Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Oncol. 2010;102(3):209–14.PubMedCrossRef
46.
Chan AW, Tetzlaff JM, Altman DG, Dickersin K, Moher D. SPIRIT 2013: new guidance for content of clinical trial protocols. Lancet. 2013;381(9861):91–2.PubMedCrossRef
47.
Meyer J. IMRT, IGRT, SBRT : advances in the treatment planning and delivery of radiotherapy. Basel. New York: Karger; 2007.CrossRef
48.
Kirichenko A, Gayou O, Parda D, Kudithipudi V, Tom K, Khan A, Abrams P, Szramowski M, Oliva J, Monga D, et al. Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors. HPB (Oxford). 2016;18(1):88–97.CrossRef
49.
Habermehl D, Naumann P, Bendl R, Oelfke U, Nill S, Debus J, Combs SE. Evaluation of inter- and intrafractional motion of liver tumors using interstitial markers and implantable electromagnetic radiotransmitters in the context of image-guided radiotherapy (IGRT) - the ESMERALDA trial. Radiat Oncol. 2015;10:143.PubMedPubMedCentralCrossRef
50.
51.
Toesca DA, Osmundson EC, Eyben RV, Shaffer JL, Lu P, Koong AC, Chang DT. Central liver toxicity after SBRT: An expanded analysis and predictive nomogram. Radiother Oncol. 2016.
52.
Seyal AR, Gonzalez-Guindalini FD, Arslanoglu A, Harmath CB, Lewandowski RJ, Salem R, Yaghmai V. Reproducibility of mRECIST in assessing response to transarterial radioembolization therapy in hepatocellular carcinoma. Hepatology. 2015;62(4):1111–21.PubMedCrossRef
53.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed
54.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60.PubMedCrossRef
55.
56.
Zhang X, Wang K, Wang M, Yang G, Ye X, Wu M, Cheng S. Transarterial chemoembolization (TACE) combined with sorafenib versus TACE for hepatocellular carcinoma with portal vein tumor thrombus: a systematic review and meta-analysis. Oncotarget. 2017;8(17):29416–27.PubMedPubMedCentral
57.
Yoon SM, Lim YS, Park MJ, Kim SY, Cho B, Shim JH, Kim KM, Lee HC, Chung YH, Lee YS, et al. Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS One. 2013;8(11):e79854.PubMedPubMedCentralCrossRef
58.
Shiozawa K, Watanabe M, Ikehara T, Matsukiyo Y, Kogame M, Kishimoto Y, Okubo Y, Makino H, Tsukamoto N, Igarashi Y, et al. Comparison of percutaneous radiofrequency ablation and CyberKnife((R)) for initial solitary hepatocellular carcinoma: a pilot study. World J Gastroenterol. 2015;21(48):13490–9.PubMedPubMedCentralCrossRef
59.
Barry A, Knox JJ, Wei AC, Dawson LA. Can stereotactic body radiotherapy effectively treat hepatocellular carcinoma? J Clin Oncol. 2016;34(5):404–8.PubMedCrossRef
60.
Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106(8):1653–63.PubMedCrossRef
61.
Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and safety of Transarterial chemoembolization plus external beam radiotherapy vs Sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol. 2018.
Metadata
Title
Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial
Authors
Liang-Cheng Chen
Wen-Yen Chiou
Hon-Yi Lin
Moon-Sing Lee
Yuan-Chen Lo
Li-Wen Huang
Chun-Ming Chang
Tsung-Hsing Hung
Chih-Wen Lin
Kuo-Chih Tseng
Dai-Wei Liu
Feng-Chun Hsu
Shih-Kai Hung
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5461-3

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