Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a primary liver cancer believed to originate from primary stem cells.[1] This cancer is increasing in its incidence likely due to the increase in the incidence of chronic hepatitis.[2] The treatment of choice is surgery and therefore every patient must undergo evaluation for surgery. However, most patients present in an inoperable stage[3] and the intent of treatment becomes palliative, an important goal of therapy being preserving the liver function for as long as possible. To achieve this, many liver-directed therapies (LDTs) have come up that can stall tumor progression. These include transarterial chemoembolization (TACE), transarterial radioembolization, radiofrequency ablation (RFA), intra-arterial chemotherapy, targeted drugs (sorafenib and lenvatinib), and IO drugs (nivolumab and pembrolizumab). In this therapeutic armamentarium, stereotactic body radiation therapy (SBRT) is an important addition. There is no specific experimental data that compare and contrast the above-mentioned modalities, and therefore, the treatment offered at most institutions is largely empirical and dependent on expertise and preferences of treating team. In this paper, we attempt to delineate the merits and relative strengths of SBRT for HCC.

SBRT is defined as a method of external beam radiotherapy that accurately delivers a high radiation dose to a target in one or few treatment fractions.[4] It is done by focusing high-energy radiation beams from multiple directions via specialized linear accelerators (Trubeam, Trilogy, Novalis, Edge, Synergy, Cyberknife, and others) that provide precise delivery of dose to prespecified target by shaping of beam perfectly on to the target and by checking for even minor errors in the position of target at the time of radiation delivery by image guidance technology. Typically, SBRT treatment sessions are 3–10 in number, and the dose delivered in each fraction is 5 Gy or more depending on the best compromise reached between radiation dose to the target and normal tissues on the computerized planning system. Smaller the tumor, larger the dose that can be delivered into it without compromising liver function. The aim is to ablate the tumor without damage to the functioning liver tissue.

Let us examine the role of SBRT in various clinical situations with HCC.

Publikationsverlauf

Eingereicht: 17. Februar 2020

Angenommen: 01. Juni 2020

Artikel online veröffentlicht:
17. Mai 2021

• References

• 1 Tummala KS, Brandt M, Teijeiro A, Graña O, Schwabe RF, Perna C. et al. Hepatocellular carcinomas originate predominantly from hepatocytes and benign lesions from hepatic progenitor cells. Cell Rep 2017; 19: 584-600
• 2 Acharya SK. Epidemiology of hepatocellular carcinoma in India. J Clin Exp Hepatol 2014; 4: S27-33
• 3 Kumar R, Kumar Saraswat M, Chander Sharma B, Sakhuja P, Sarin SK. Characteristics of hepatocellular carcinoma in India: A retrospective analysis of 191 cases. QJM 2008; 101: 479-85
• 4 Guckenberger M, Andratschke N, Alheit H, Holy R, Moustakis C, Nestle U. et al. Definition of stereotactic body radiotherapy: Principles and practice for the treatment of stage I non-small cell lung cancer. Strahlenther Onkol 2014; 190: 26-33
• 5 Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS. et al. Outcomesww after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J Clin Oncol 2016; 34: 452-9
• 6 Rajyaguru DJ, Borgert AJ, Smith AL, Thomes RM, Conway PD, Halfdanarson TR. et al. Radiofrequency ablation versus stereotactic body radiotherapy for localized hepatocellular carcinoma in nonsurgically managed patients: Analysis of the national cancer database. J Clin Oncol 2018; 36: 600-8
• 7 Bibault JE, Dewas S, Vautravers-Dewas C, Hollebecque A, Jarraya H, Lacornerie T. et al. Stereotactic body radiation therapy for hepatocellular carcinoma: Prognostic factors of local control, overall survival, and toxicity. PLoS One 2013; 8: e77472
• 8 Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ, Zook J. et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2011; 81: e447-53
• 9 Jung J, Yoon SM, Kim SY, Cho B, Park JH, Kim SS. et al. Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: Clinical and dose-volumetric parameters. Radiat Oncol 2013; 8: 249
• 10 Sanuki N, Takeda A, Mizuno T, Oku Y, Eriguchi T, Iwabuchi S. et al. Tumor response on CT following hypofractionated stereotactic ablative body radiotherapy for small hypervascular hepatocellular carcinoma with cirrhosis. AJR Am J Roentgenol 2013; 201: W812-20
• 11 Higgins H, Berger DL. RFA for liver tumors: Does it really work?. Oncologist 2006; 11: 801-8
• 12 Méndez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJ, Nowak PC. et al. Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study. Acta Oncol 2006; 45: 831-7
• 13 Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH. et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer 2012; 118: 5424-31
• 14 Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK. et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 2013; 31: 1631-9
• 15 Culleton S, Jiang H, Haddad CR, Kim J, Brierley J, Brade A. et al. Outcomes following definitive stereotactic body radiotherapy for patients with Child-Pugh B or C hepatocellular carcinoma. Radiother Oncol 2014; 111: 412-7
• 16 Scorsetti M, Comito T, Cozzi L, Clerici E, Tozzi A, Franzese C. et al. The challenge of inoperable hepatocellular carcinoma (HCC): Results of a single-institutional experience on stereotactic body radiation therapy (SBRT). J Cancer Res Clin Oncol 2015; 141: 1301-9
• 17 Huo YR, Eslick GD. Transcatheter arterial chemoembolization plus radiotherapy compared with chemoembolization alone for hepatocellular carcinoma: A systematic review and meta-analysis. JAMA Oncol 2015; 1: 756-65
• 18 Buckstein M, Kim E, Fischman A, Blacksburg S, Facciuto M, Schwartz M. et al. Stereotactic body radiation therapy following transarterial chemoembolization for unresectable hepatocellular carcinoma. J Gastrointest Oncol 2018; 9: 734-40
• 19 Hoekstra J, Janssen HL. Vascular liver disorders (II): Portal vein thrombosis. Neth J Med 2009; 67: 46-53
• 20 Lin CS, Jen YM, Chiu SY, Hwang JM, Chao HL, Lin HY. et al. Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 2006; 36: 212-7
• 21 Xi M, Zhang L, Zhao L, Li QQ, Guo SP, Feng ZZ. et al. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One 2013; 8: e63864
• 22 Kang J, Nie Q, DU R, Zhang L, Zhang J, Li Q. et al. Stereotactic body radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis. Mol Clin Oncol 2014; 2: 43-50
• 23 Sapisochin G, Barry A, Doherty M, Fischer S, Goldaracena N, Rosales R. et al. Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol 2017; 67: 92-9
• 24 Nugent FW, Qamar A, Stuart KE, Galuski K, Flacke S, Molgaard C. A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC). J Clin Oncol 2017; 35 et al. suppl 4S abstract 223 223