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Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation

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Abstract

Background

Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx.

Patients and methods

Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40–50 Gy delivered in 4–6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT.

Results

Median size of original tumors was 3.2 cm (2.0–8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0–3.2) in the explanted livers (p < 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx.

Conclusion

SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.

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Abbreviations

TACE:

Trans-arterial chemoembolization

HCC:

Hepatocellular carcinoma

SBRT:

Stereotactic body radiation therapy

RFA:

Radiofrequency ablation

RILD:

Radiation induced liver disease

MELD:

Model for end-stage liver disease

PTV:

Planned target volume

AFP:

Alpha fetoprotein

References

  1. El-Serag HB, Mason AC (1999) Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750

    Article  CAS  PubMed  Google Scholar 

  2. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699

    Article  CAS  Google Scholar 

  3. Abdelmaksoud AH, Mandooh S, Nabeel MM, Elbaz TM, Shousha HI, Monier A et al (2017) Portal vein thrombosis in unresectable Hcc cases: a single center study of prognostic factors and management in 140 patients. Asian Pac J Cancer Prev 18(1):183–188

    PubMed  PubMed Central  Google Scholar 

  4. Sellers MT, Huggins S, Kegley K, Pollinger HS, Shrestha R, Johnson MW et al (2013) Multivariate analysis of prognostic factors for survival following doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 24(5):647–654

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lopez PM, Villanueva A, Llovet JM (2006) Systematic review: evidence-based management of hepatocellular carcinoma—an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 23:1535–1547

    Article  CAS  PubMed  Google Scholar 

  6. Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW (2013) Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol 19(43):7515–7530

    Article  PubMed  PubMed Central  Google Scholar 

  7. https://optn.transplant.hrsa.gov/media/1140/policy_notice_12-2014.pdf

  8. Herfarth KK, Debus J, Lohr F, Bahner ML, Rhein B, Fritz P et al (2001) Stereotactic single dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170

    Article  CAS  Google Scholar 

  9. Rusthoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigenberg SJ et al (2009) Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 27:1572–1578

    Article  PubMed  Google Scholar 

  10. Hoyer M, Roed H, Traberg Hansen A, Ohlhuis L, Petersen J, Nellemann H et al (2006) Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 45:823–830

    Article  PubMed  Google Scholar 

  11. Wulf J, Hädinger U, Oppitz U, Thiele W, Ness-Dourdoumas R, Flentje M (2001) Stereotactic radiotherapy of targets in the lung and liver. Strahlenther Onkol 177:645–655

    Article  CAS  PubMed  Google Scholar 

  12. Méndez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJ, Nowak PC et al (2006) Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I–II study. Acta Oncol 45:831–837

    Article  PubMed  Google Scholar 

  13. Méndez Romero A, Wunderink W, van Os RM, Nowak PJ, Heijmen BJ, Nuyttens JJ et al (2008) Quality of life after stereotactic body radiation therapy for primary and metastatic liver tumors. Int J Radiat Oncol Biol Phys 70:1447–1452

    Article  PubMed  Google Scholar 

  14. Chiba T, Tokuuye K, Matsuzaki Y, Sugahara S, Chuganji Y, Kagei K et al (2005) Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients. Clin Cancer Res 11:3799–3805

    Article  PubMed  Google Scholar 

  15. Kirichenko A, Gayou O, Parda D, Kudithipudi V, Tom K, Khan A et al (2016) Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors. HPB (Oxford) 18:88–97

    Article  Google Scholar 

  16. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 4.0, (http://ctep.cancer.gov), Publish Date: May 28, 2009

  17. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470

    Article  CAS  PubMed  Google Scholar 

  18. Gayou O, Day E, Kirichenko A (2012) A method for registration of single photon emission computed tomography (SPECT) and computed tomography (CT) images for liver stereotactic radiotherapy (SRT). Med Phys 39:7398–7401

    Article  PubMed  Google Scholar 

  19. Urata K, Kawasaki S, Matsunami H, Hashikura Y, Ikegami T, Ishizone S et al (1995) Calculation of child and adult standard liver volume for liver transplantation. Hepatology 21:1317–1321

    Article  CAS  PubMed  Google Scholar 

  20. Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting C et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 68:13–23

    Article  PubMed  Google Scholar 

  21. Penna C, Nordlinger B (2002) Colorectal metastasis (liver and lung). Surg Clin North Am 82:1075–1090

    Article  PubMed  Google Scholar 

  22. Leibel SA, Pajak TF, Massullo V, Order SE, Komaki RU, Chang CH (1987) A comparison of misonidazole sensitized radiation therapy to radiation therapy alone for the palliation of hepatic metastases: results of a Radiation Therapy Oncology Group randomized prospective trial. Int J Radiat Oncol Biol Phys 13:1057–1064

    Article  CAS  PubMed  Google Scholar 

  23. Russell AH, Clyde C, Wasserman TH, Turner SS, Rotman M (1993) Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol. Int J Radiat Oncol Biol Phys 27:117–123

    Article  CAS  PubMed  Google Scholar 

  24. Goodman KA, Wiegner EA, Maturen KE, Zhang Z, Mo Q, Yang G (2010) Dose-escalation study of single-fraction stereotactic body radiotherapy for liver malignancies. Int J Radiat Oncol Biol Phys 78:486–493

    Article  PubMed  Google Scholar 

  25. Facciuto ME, Singh MK, Rochon C, Sharma J, Gimenez C, Katta U et al (2012) Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response. J Surg Oncol 105:692–698

    Article  PubMed  Google Scholar 

  26. Keane FK, Wo JY, Zhu AX, Hong TS (2016) Liver-directed radiotherapy for hepatocellular carcinoma. Liver Cancer 5:198–209

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sanuki N, Takeda A, Oku Y, Mizuno T, Aoki Y, Eriguchi T et al (2014) Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol 53:399–404

    Article  PubMed  Google Scholar 

  28. Honda Y, Kimura T, Aikata H, Kobayashi T, Fukuhara T, Masaki K et al (2013) Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. J Gastroenterol Hepatol 28:530–536

    Article  PubMed  Google Scholar 

  29. Klein J, Dawson LA, Jiang H, Kim J, Dinniwell R, Brierley J et al (2015) Prospective longitudinal assessment of quality of life for liver cancer patients treated with stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 93:16–25

    Article  Google Scholar 

  30. Cheng JC, Wu JK, Huang CM, Liu HS, Huang DY, Cheng SH et al (2002) Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: Dosimetric analysis and implication. Int J Radiat Oncol Biol Phys 54:156–162

    Article  PubMed  Google Scholar 

  31. Cheng JC, Wu JK, Lee PC, Liu HS, Jian JJ, Lin YM et al (2004) Biologic susceptibility of hepatocellular carcinoma in patients treated with radiotherapy to radiation induced liver disease. Int J Radiat Oncol Biol Phys 60:1502–1509

    Article  PubMed  Google Scholar 

  32. Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ et al (2006) Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 65:426–434

    Article  PubMed  Google Scholar 

  33. Sapisochin G, Barry A, Doherty M, Fischer S, Goldaracena N, Rosales R et al (2017) Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis. J Hepatol 67(1):92–99

    Article  PubMed  Google Scholar 

  34. Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917

    Article  Google Scholar 

  35. Millonig G, Graziadei IW, Freund MC, Jaschke W, Stadlmann S, Ladurner R et al (2007) Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 13:272–279

    Article  PubMed  Google Scholar 

  36. Alba E, Valls C, Dominguez J, Martinez L, Escalante E, Lladó L, Serrano T (2008) Transcatheter arterial chemoembolization in patients with hepatocellular carcinoma on the waiting list for orthotopic liver transplantation. AJR Am J Roentgenol 190:1341–1348

    Article  PubMed  Google Scholar 

  37. Tsochatzis E, Garcovich M, Marelli L, Papastergiou V, Fatourou E, Rodriguez-Peralvarez ML et al (2013) Transarterial embolization as neo-adjuvant therapy pretransplantation in patients with hepatocellular carcinoma. Liver Int 33:944–949

    Article  CAS  PubMed  Google Scholar 

  38. O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM (2012) Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation. Liver Transpl 18:949–954

    Article  PubMed  Google Scholar 

  39. Fujioka M, Nakashima Y, Nakashima O, Kojiro M (2001) Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma. Hepatology 34:1128–1134

    Article  CAS  PubMed  Google Scholar 

  40. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33:1394–1403

    Article  CAS  PubMed  Google Scholar 

  41. Toso C, Asthana S, Bigam DL, Shapiro AM, Kneteman NM (2009) Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the Scientific Registry of Transplant Recipients database. Hepatology 49:832–838

    Article  PubMed  Google Scholar 

  42. Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M et al (2008) Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 85:1726–1732

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA

    Tadahiro Uemura, Molly Vincent, Lorenzo Machado & Ngoc Thai

  2. Radiation Oncology, Allegheny General Hospital, Pittsburgh, USA

    Alexander Kirichenko

  3. Pathology, Allegheny General Hospital, Pittsburgh, USA

    Mark Bunker

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  1. Tadahiro Uemura
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  2. Alexander Kirichenko
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Correspondence to Tadahiro Uemura.

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The authors who have taken part in this study declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

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Uemura, T., Kirichenko, A., Bunker, M. et al. Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation. World J Surg 43, 886–893 (2019). https://doi.org/10.1007/s00268-018-4829-x

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  • DOI: https://doi.org/10.1007/s00268-018-4829-x

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