Stereotactic body radiation therapy for hepatocellular carcinoma: prognostic factors of local control, overall survival, and toxicity

Jean-Emmanuel Bibault, Sylvain Dewas, Claire Vautravers-Dewas, Antoine Hollebecque, Hajer Jarraya, Thomas Lacornerie, Eric Lartigau, Xavier Mirabel, Jean-Emmanuel Bibault, Sylvain Dewas, Claire Vautravers-Dewas, Antoine Hollebecque, Hajer Jarraya, Thomas Lacornerie, Eric Lartigau, Xavier Mirabel

Abstract

Purpose: Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been evaluated in several recent studies. The CyberKnife(®) is an SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the prognostic factors for local control and overall survival following this treatment.

Patients and methods: 75 patients with 96 liver-confined HCC were treated with SBRT at the Oscar Lambret Comprehensive Cancer Center. Fiducials were implanted in the liver before treatment and were used as markers to track the lesion's movement. Treatment response was scored according to RECIST v1.1. Local control and overall survival were calculated using the Kaplan and Meier method. A stepwise multivariate analysis (Cox regression) of prognostic factors was performed for local control and overall survival.

Results: There were 67 patients with Child-Turcotte-Pugh (CTP) Class A and eight patients with CTP Class B. Treatment was administered in three sessions. A total dose of 40-45 Gy to the 80% isodose line was delivered. The median follow-up was 10 months (range, 3-49 months). The local control rate was 89.8% at 1 and 2 years. Overall survival was 78.5% and 50.4% at 1 and 2 years, respectively. Toxicity mainly consisted of grade 1 and grade 2 events. Higher alpha-fetoprotein (aFP) levels were associated with less favorable local control (HR=1.001; 95% CI [1.000, 1.002]; p=0.0063). A higher dose was associated with better local control (HR=0.866; 95% CI [0.753, 0.996]; p=0.0441). A Child-Pugh score higher than 5 was associated with worse overall survival (HR= 3.413; 95% CI [1.235, 9.435]; p=0.018).

Conclusion: SBRT affords good local tumor control and higher overall survival rates than other historical controls (best supportive care or sorafenib). High aFP levels were associated with lesser local control, but a higher treatment dose improved local control.

Conflict of interest statement

Competing Interests: The radiation therapy department at the Oscar Lambret Comprehensive Cancer Center has a clinical research program partially funded by Accuray. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Kaplan Meier curves for local…
Figure 1. Kaplan Meier curves for local control and overall survival.

References

    1. Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R et al. (2006) The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology 43: 1303–1310. doi:10.1002/hep.21176. PubMed: .
    1. Villanueva A, Hernandez-Gea V, Llovet JM (2013) Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat. Rev Gastroenterol Hepatol 10: 34–42. doi:10.1038/nrgastro.2012.199.
    1. Lencioni R, Crocetti L (2012) Local-regional treatment of hepatocellular carcinoma. Radiology 262: 43–58. doi:10.1148/radiol.11110144. PubMed: .
    1. Lencioni R (2012) Chemoembolization for hepatocellular carcinoma. Semin Oncol 39: 503–509. doi:10.1053/j.seminoncol.2012.05.004. PubMed: .
    1. Xie B, Wang DH, Spechler SJ (2012) Sorafenib for treatment of hepatocellular carcinoma: a systematic review. Dig Dis Sci 57: 1122–1129. doi:10.1007/s10620-012-2136-1. PubMed: .
    1. Feng M, Ben-Josef E (2011) Radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol 21: 271–277. doi:10.1016/j.semradonc.2011.05.002. PubMed: .
    1. Qian J, Feng G-S, Vogl T (2003) Combined interventional therapies of hepatocellular carcinoma. World J Gastroenterol 9: 1885–1891. PubMed: .
    1. Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53: 1020–1022. doi:10.1002/hep.24199. PubMed: .
    1. European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma (2012). J Hepatol 56: 908–943. doi:10.1016/j.jhep.2011.12.001. PubMed: .
    1. Comet B, Kramar A, Faivre-Pierret M, Dewas S, Coche-Dequeant B et al. (2012) Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head-and-neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys 84: 203–209. doi:10.1016/j.ijrobp.2011.11.054. PubMed: .
    1. Dewas S, Bibault JE, Mirabel X, Nickers P, Castelain B et al. (2011) Robotic image-guided reirradiation of lateral pelvic recurrences: preliminary results. Radiol Oncol 6: 77. doi:10.1186/1748-717X-6-77. PubMed: .
    1. Blomgren H, Lax I, Näslund I, Svanström R (1995) Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator: clinical experience of the first thirty-one patients. Acta Oncol 34: 861–870. doi:10.3109/02841869509127197. PubMed: .
    1. Vautravers-Dewas C, Dewas S, Bonodeau F, Adenis A, Lacornerie T et al. (2011) Image-guided robotic stereotactic body radiation therapy for liver metastases: is there a dose response relationship? Int J Radiat Oncol Biol Phys 81: e39–e47. doi:10.1016/j.ijrobp.2010.12.047. PubMed: .
    1. Klein J, Dawson LA (2012) Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2012.08.043.
    1. Dewas S, Bibault J-E, Mirabel X, Fumagalli I, Kramar A et al. (2012) Prognostic factors affecting local control of hepatic tumors treated by Stereotactic Body Radiation Therapy. Radiol Oncol 7: 166. doi:10.1186/1748-717X-7-166. PubMed: .
    1. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R et al. (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference European Association for the Study of the Liver J Hepatol 35: 421–430
    1. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30: 52–60. doi:10.1055/s-0030-1247132. PubMed: .
    1. Common NCI Terminology Criteria for Adverse Events (CTCAE) v.4 (n.d.). Available: .
    1. Kang J-K, Kim M-S, Cho CK, Yang KM, Yoo HJ et al. (2012) Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. Available: Accessed 25 September 2012 PubMed: .
    1. O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB et al. (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. doi:10.1002/lt.23439. PubMed: .
    1. Huang W-Y, Jen Y-M, Lee M-S, Chang L-P, Chen C-M et al. (2012) Stereotactic body radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 84: 355–361. doi:10.1016/j.ijrobp.2011.11.058. PubMed: .
    1. Méndez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJM 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. doi:10.1080/02841860600897934. PubMed: .
    1. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B et al. (2008) Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 26: 657–664. doi:10.1200/JCO.2007.14.3529. PubMed: .
    1. McGinn CJ, Ten Haken RK, Ensminger WD, Walker S, Wang S et al. (1998) Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model. J Clin Oncol 16: 2246–2252. PubMed: .
    1. Kwon JH, Bae SH, Kim JY, Choi BO, Jang HS et al. (2010) 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 10: 475. doi:10.1186/1471-2407-10-475. PubMed: .
    1. Seo YS, Kim M-S, Yoo SY, Cho CK, Choi CW et al. (2010) Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Oncol 102: 209–214. doi:10.1002/jso.21593. PubMed: .
    1. Andolino DL, Johnson CS, Maluccio M, Kwo P, Tector AJ et al. (2011) Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 81: e447–e453. doi:10.1016/j.ijrobp.2011.04.011. PubMed: .
    1. Bujold A, Massey CA, Kim JJ, Brierley J, Cho C et al. (2013) Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma. J Clin Oncol 31: 1631–1639. doi:10.1200/JCO.2012.44.1659. PubMed: .
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E et al. (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378–390. doi:10.1056/NEJMoa0708857. PubMed: .
    1. Cheng A-L, Kang Y-K, Chen Z, Tsao C-J, Qin S et al. (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: 25–34. doi:10.1016/S1470-2045(08)70285-7. PubMed: .

Source: PubMed

3
Předplatit