Skip to main content
Top
Published in: Strahlentherapie und Onkologie 3/2019

01-03-2019 | Original Article

Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B–C hepatocellular carcinoma

Authors: C. L. Chiang, Mark K. H. Chan, Cynthia S. Y. Yeung, Connie H. M. Ho, Francis A. S. Lee, Venus W. Y. Lee, Frank C. S. Wong, Oliver Blanck

Published in: Strahlentherapie und Onkologie | Issue 3/2019

Login to get access

Abstract

Purpose

We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B–C hepatocellular carcinoma (HCC).

Patients and methods

Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child–Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6 × 5–8 Gy or 5–10 × 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated.

Results

The patients’ characteristics were: median age 60 years (range 28–87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0–23.6 cm) and 751 cm3 (range 41–4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/β = 10) was 37.3 Gy2 (range, 28–72 Gy2). The median follow-up time was 16.8 months (range, 3–96 months). The objective RR was 68% and the 1‑year LC rate was 93.6% (95% CI, 87.6–100%). The median OS was 19.8 months (95% CI, 11.6–30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury.

Conclusion

Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B–C HCC with appropriate patient selection. Further prospective trials are warranted.
Appendix
Available only for authorised users
Literature
8.
go back to reference Omata M, Lesmana LA, Tateishi R, Chen P‑J, Lin S‑M, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RTP, Shiina S, Cheng AL, Jia J‑D, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4(2):439–474. https://doi.org/10.1007/s12072-010-9165-7 CrossRefPubMedPubMedCentral Omata M, Lesmana LA, Tateishi R, Chen P‑J, Lin S‑M, Yoshida H, Kudo M, Lee JM, Choi BI, Poon RTP, Shiina S, Cheng AL, Jia J‑D, Obi S, Han KH, Jafri W, Chow P, Lim SG, Chawla YK, Budihusodo U, Gani RA, Lesmana CR, Putranto TA, Liaw YF, Sarin SK (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4(2):439–474. https://​doi.​org/​10.​1007/​s12072-010-9165-7 CrossRefPubMedPubMedCentral
10.
go back to reference Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet 359(9319):1734–1739. https://doi.org/10.1016/s0140-6736(02)08649-x CrossRefPubMed Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet 359(9319):1734–1739. https://​doi.​org/​10.​1016/​s0140-6736(02)08649-x CrossRefPubMed
12.
go back to reference Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J‑F, de Oliveira AC, Santoro A, Raoul J‑L, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz J‑F, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390. https://doi.org/10.1056/NEJMoa0708857 CrossRefPubMed Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J‑F, de Oliveira AC, Santoro A, Raoul J‑L, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz J‑F, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390. https://​doi.​org/​10.​1056/​NEJMoa0708857 CrossRefPubMed
13.
go back to reference Cheng A‑L, Kang Y‑K, Chen Z, Tsao C‑J, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang T‑S, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z (2009) 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 10(1):25–34. https://doi.org/10.1016/s1470-2045(08)70285-7 CrossRefPubMed Cheng A‑L, Kang Y‑K, Chen Z, Tsao C‑J, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang T‑S, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z (2009) 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 10(1):25–34. https://​doi.​org/​10.​1016/​s1470-2045(08)70285-7 CrossRefPubMed
16.
22.
go back to reference Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, Imajo K, Aoki Y, Saito H, Kunieda E (2016) Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer 122(13):2041–2049. https://doi.org/10.1002/cncr.30008 CrossRefPubMed Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, Imajo K, Aoki Y, Saito H, Kunieda E (2016) Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer 122(13):2041–2049. https://​doi.​org/​10.​1002/​cncr.​30008 CrossRefPubMed
23.
go back to reference Honda Y, Kimura T, Aikata H, Nakahara T, Naeshiro N, Miyaki D, Nagaoki Y, Kawaoka T, Takaki S, Hiramatsu A, Waki K, Ishikawa M, Kakizawa H, Kenjo M, Awai K, Nagata Y, Chayama K (2014) Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. Hepatogastroenterology 61(129):31–36PubMed Honda Y, Kimura T, Aikata H, Nakahara T, Naeshiro N, Miyaki D, Nagaoki Y, Kawaoka T, Takaki S, Hiramatsu A, Waki K, Ishikawa M, Kakizawa H, Kenjo M, Awai K, Nagata Y, Chayama K (2014) Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. Hepatogastroenterology 61(129):31–36PubMed
24.
go back to reference Jacob R, Turley F, Redden DT, Saddekni S, Aal AKA, Keene K, Yang E, Zarzour J, Bolus D, Smith JK, Gray S, White J, Eckhoff DE, DuBay DA (2015) Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥3 cm. HPB (Oxford) 17(2):140–149. https://doi.org/10.1111/hpb.12331 CrossRef Jacob R, Turley F, Redden DT, Saddekni S, Aal AKA, Keene K, Yang E, Zarzour J, Bolus D, Smith JK, Gray S, White J, Eckhoff DE, DuBay DA (2015) Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥3 cm. HPB (Oxford) 17(2):140–149. https://​doi.​org/​10.​1111/​hpb.​12331 CrossRef
25.
go back to reference Su T‑S, Lu H‑Z, Cheng T, Zhou Y, Huang Y, Gao Y‑C, Tang M‑Y, Jiang H‑Y, Lian Z‑P, Hou E‑C, Liang P (2016) Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma 〉5 cm. BMC Cancer 16:834. https://doi.org/10.1186/s12885-016-2894-9 CrossRefPubMedPubMedCentral Su T‑S, Lu H‑Z, Cheng T, Zhou Y, Huang Y, Gao Y‑C, Tang M‑Y, Jiang H‑Y, Lian Z‑P, Hou E‑C, Liang P (2016) Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma 〉5 cm. BMC Cancer 16:834. https://​doi.​org/​10.​1186/​s12885-016-2894-9 CrossRefPubMedPubMedCentral
32.
go back to reference Chow PKH, Gandhi M, Tan S‑B, Khin MW, Khasbazar A, Ong J, Choo SP, Cheow PC, Chotipanich C, Lim K, Lesmana LA, Manuaba TW, Yoong BK, Raj A, Law CS, Cua IHY, Lobo RR, Teh CSC, Kim YH, Jong YW, Han H‑S, Bae S‑H, Yoon H‑K, Lee R‑C, Hung C‑F, Peng C‑Y, Liang P‑C, Bartlett A, Kok KYY, Thng C‑H, Low AS-C, Goh ASW, Tay KH, Lo RHG, Goh BKP, Ng DCE, Lekurwale G, Liew WM, Gebski V, Mak KSW, Soo KC, Asia-Pacific Hepatocellular Carcinoma Trials Group (2018) SIRveNIB: Selective internal radiation therapy versus Sorafenib in asia-pacific patients with Hepatocellular carcinoma. J Clin Oncol 36(19):1913–1921. https://doi.org/10.1200/jco.2017.76.0892 CrossRefPubMed Chow PKH, Gandhi M, Tan S‑B, Khin MW, Khasbazar A, Ong J, Choo SP, Cheow PC, Chotipanich C, Lim K, Lesmana LA, Manuaba TW, Yoong BK, Raj A, Law CS, Cua IHY, Lobo RR, Teh CSC, Kim YH, Jong YW, Han H‑S, Bae S‑H, Yoon H‑K, Lee R‑C, Hung C‑F, Peng C‑Y, Liang P‑C, Bartlett A, Kok KYY, Thng C‑H, Low AS-C, Goh ASW, Tay KH, Lo RHG, Goh BKP, Ng DCE, Lekurwale G, Liew WM, Gebski V, Mak KSW, Soo KC, Asia-Pacific Hepatocellular Carcinoma Trials Group (2018) SIRveNIB: Selective internal radiation therapy versus Sorafenib in asia-pacific patients with Hepatocellular carcinoma. J Clin Oncol 36(19):1913–1921. https://​doi.​org/​10.​1200/​jco.​2017.​76.​0892 CrossRefPubMed
33.
go back to reference Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller F, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ (2016) Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 151(6):1155–1163. https://doi.org/10.1053/j.gastro.2016.08.029 CrossRefPubMedPubMedCentral Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, Mulcahy MF, Baker T, Abecassis M, Miller F, Yaghmai V, Sato K, Desai K, Thornburg B, Benson AB, Rademaker A, Ganger D, Kulik L, Lewandowski RJ (2016) Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 151(6):1155–1163. https://​doi.​org/​10.​1053/​j.​gastro.​2016.​08.​029 CrossRefPubMedPubMedCentral
34.
go back to reference Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH, Sato KT, Wang E, Gupta R, Benson AB, Newman SB, Omary RA, Abecassis M, Kulik L (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: A comprehensive report of long-term outcomes. Gastroenterology 138(1):52–64. https://doi.org/10.1053/j.gastro.2009.09.006 CrossRefPubMed Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH, Sato KT, Wang E, Gupta R, Benson AB, Newman SB, Omary RA, Abecassis M, Kulik L (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: A comprehensive report of long-term outcomes. Gastroenterology 138(1):52–64. https://​doi.​org/​10.​1053/​j.​gastro.​2009.​09.​006 CrossRefPubMed
39.
go back to reference Vincenzi B, Di Maio M, Silletta M, D’Onofrio L, Spoto C, Piccirillo MC, Daniele G, Comito F, Maci E, Bronte G, Russo A, Santini D, Perrone F, Tonini G (2015) Prognostic relevance of objective response according to EASL criteria and mRECIST criteria in hepatocellular carcinoma patients treated with loco-regional therapies: A literature-based meta-analysis. PLoS ONE 10(7):e133488. https://doi.org/10.1371/journal.pone.0133488 CrossRefPubMedPubMedCentral Vincenzi B, Di Maio M, Silletta M, D’Onofrio L, Spoto C, Piccirillo MC, Daniele G, Comito F, Maci E, Bronte G, Russo A, Santini D, Perrone F, Tonini G (2015) Prognostic relevance of objective response according to EASL criteria and mRECIST criteria in hepatocellular carcinoma patients treated with loco-regional therapies: A literature-based meta-analysis. PLoS ONE 10(7):e133488. https://​doi.​org/​10.​1371/​journal.​pone.​0133488 CrossRefPubMedPubMedCentral
41.
go back to reference Gkika E, Bettinger D, Krafft L, Schultheiss M, Neeff HP, Maruschke L, Schulenburg M, Adebahr S, Kirste S, Nestle U, Thimme R, Grosu A‑L, Brunner TB (2018) The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy. Strahlenther Onkol. https://doi.org/10.1007/s00066-017-1256-0 CrossRefPubMed Gkika E, Bettinger D, Krafft L, Schultheiss M, Neeff HP, Maruschke L, Schulenburg M, Adebahr S, Kirste S, Nestle U, Thimme R, Grosu A‑L, Brunner TB (2018) The role of albumin–bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy. Strahlenther Onkol. https://​doi.​org/​10.​1007/​s00066-017-1256-0 CrossRefPubMed
Metadata
Title
Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B–C hepatocellular carcinoma
Authors
C. L. Chiang
Mark K. H. Chan
Cynthia S. Y. Yeung
Connie H. M. Ho
Francis A. S. Lee
Venus W. Y. Lee
Frank C. S. Wong
Oliver Blanck
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 3/2019
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-018-1391-2

Other articles of this Issue 3/2019

Strahlentherapie und Onkologie 3/2019 Go to the issue