Clinical outcomes and prognostic factors of cyberknife stereotactic body radiation therapy for unresectable hepatocellular carcinoma

Jenny Que, Hsing-Tao Kuo, Li-Ching Lin, Kuei-Li Lin, Chia-Hui Lin, Yu-Wei Lin, Ching-Chieh Yang, Jenny Que, Hsing-Tao Kuo, Li-Ching Lin, Kuei-Li Lin, Chia-Hui Lin, Yu-Wei Lin, Ching-Chieh Yang

Abstract

Background: Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with hepatocellular carcinoma (HCC) when curative treatments cannot be applied. In this study, we report our clinical experience with Cyberknife SBRT for unresectable HCC and evaluate the efficacy and clinical outcomes of this highly sophisticated treatment technology.

Methods: Between 2008 and 2012, 115 patients with unresectable HCC treated with Cyberknife SBRT were retrospectively analyzed. Doses ranged from 26 Gy to 40 Gy were given in 3 to 5 fractions for 3 to 5 consecutive days. The cumulative probability of survival was calculated according to the Kaplan-Meier method and compared using log-rank test. Univariate and multivariate analysis were performed using Cox proportional hazard models.

Results: The median follow-up was 15.5 months (range, 2-60 months). Based on Response Evaluation and Criteria in Solid Tumors (RECIST). We found that 48.7 % of patients achieved a complete response and 40 % achieved a partial response. Median survival was 15 months (4-25 months). Overall survival (OS) at 1- and 2-years was 63.5 %(54-71.5 %) and 41.3 % (31.6-50.6 %), respectively, while 1- and 2- years Progression-free Survival (PFS) rates were 42.8 %(33.0-52.2 %) and 38.8 % (29.0-48.4 %). Median progression was 6 months (3-16 months). In-field recurrence free survival at 1 and 2 years was 85.3 % (76.2-91.1 %) and 81.6 % (72.2-88.6 %), respectively, while the 1- and 2-years out-field recurrence free survival were 52.5 % (41.2-60.8 %) and 49.5 %(38.9-59.2 %), respectively. Multivariate analysis revealed that Child-Pugh score (A vs. B), Portal vein tumor thrombosis (positive vs. negative), Tumor size (≤4 cm vs >4-9 cm /≥10 cm), and tumor response after SBRT (CR vs. PR/stable) were independent predictors of OS. Acute toxicity was mostly transient and tolerable.

Conclusions: Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity. These results suggested that Cyberknife SBRT can be a good alternative treatment for unresectable HCC unsuitable for standard treatment.

Keywords: Cyberknife; Hepatocellular carcinoma; Stereotactic body radiation therapy.

Figures

Fig. 1
Fig. 1
In-field recurrence free rate at 1-yr and 2-yrs were 85.3 % (76.2-91.1) and 81.6 % (71.2-88.6), respectively. Out-field recurrence free rate at 1-yr and 2-yrs were 51.5 % (41.2-60.8) and 49.5 % (38.9-59.2), respectively
Fig. 2
Fig. 2
Overall survival curve of 115 patients treated with Cyberknife SBRT. 1-yr and 2-yrs OSR were 63.5 % (54-71.5 %) and 41.3 % (31.6-50.6 %), median survival times was 15 months (4-25 mos.), While 1-yr and 2-yrs Progression-free survival rate were 42.8 % (33.0-52.2 %) and 38.8 % (29.0-48.4 %), median progressive-free survival times was 6 months, respectively

References

    1. Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917. doi: 10.1002/ijc.25516.
    1. Bruix J, Sheramn M, Practice Guidelines Committee et al. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236. doi: 10.1002/hep.20933.
    1. Bujold A, Massey C, Kim J, Brierly J, Cho C, Wong R, et al. Sequential phase I and II trials of Stereotatic body radiotherapy for locally advance hepatocellular carcinoma. J Clin Oncol. 2013;31:1631–1639. doi: 10.1200/JCO.2012.44.1659.
    1. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized trial. Lancet. 2002;359(9319):1734–1739. doi: 10.1016/S0140-6736(02)08649-X.
    1. Lo CM, Nigan H, Tso WK, Liu CL, Lam CM, Poon R, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164–1171. doi: 10.1053/jhep.2002.33156.
    1. Llovet JM, Ricci S, Mezzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390. doi: 10.1056/NEJMoa0708857.
    1. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia- Pacific region with advance hepatocellular carcinoma: A phase III randomized double-blind placebo-controlled trial. Lancet Oncol. 2009;10:25–34. doi: 10.1016/S1470-2045(08)70285-7.
    1. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Onco. 2008;20(4):657–664. doi: 10.1200/JCO.2007.14.3529.
    1. Seo YS, Kim MS, Yoo SY, Cho CK, Choi CW, Kim JH, et al. Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Onol. 2010;102:209–214.
    1. Sarfaraz M. Cyberknife robotic arm stereotactic radiosurgery. J Am Coll Radiol. 2007;4:563–565. doi: 10.1016/j.jacr.2007.05.003.
    1. Dawson LA, Jaffray DA. Advances in image-guide radiation therapy. J Clin Oncol. 2007;25:938–946. doi: 10.1200/JCO.2006.09.9515.
    1. Nuyttens JJ, Prévost JB, Praag J, Hoogeman M, Van Klaveren RJ, Levendag PC, et al. Lung tumor tracking during stereotactic radiotherapy treatment with the Cyberknife: Marker placement and early results. Acta Oncol. 2006;45:961–965. doi: 10.1080/02841860600902205.
    1. Kim JH, Park JW, Kim TH, Koh DW, Lee WJ, Kim CM. Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in patients with hepatitis B virus-related hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2007;69:813–819. doi: 10.1016/j.ijrobp.2007.04.005.
    1. Yeo W, Johnson PJ. Diagnosis prevention and management of hepatitis B virus reactivation during anticancer therapy. Hepatology. 2006;43:209–220. doi: 10.1002/hep.21051.
    1. Cheng JC, Wu JK, Lee PC, Liu HS, Jian JJ, Lin YM, et al. Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease. Int J Radiat Oncol Biol Phys. 2004;60:1502–1509. doi: 10.1016/j.ijrobp.2004.05.048.
    1. Hoogeman M, Prevost JB, Nuyttens J, Poll J, Levendag P, Hellman B, et al. Clinical accuracy of the respiratory tumor tracking system of the cyberknife: Assessment by analysis of log files. Int J Radiat Oncol Biol Phys. 2009;74:297–303. doi: 10.1016/j.ijrobp.2008.12.041.
    1. Pan CC, Kavanagh BD, Dawson A, Li XA, Das SK, Miften M, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76:S94–S100. doi: 10.1016/j.ijrobp.2009.06.092.
    1. Benedict SH, Yenice KM, Follwill D, Galvin JM, Hinson W, Kavanagh B, et al. Stereotactic body radiation therapy: The report of AAPM task group 101. Med Phys. 2010;37:4078–4100. doi: 10.1118/1.3438081.
    1. Cheng JC, Wu JK, Huang CM, Huang D, Cheng S, Lin YM. Radiation-induced liver disease after radiotherapy for hepatocellular carcinoma: Clinical manifestation and dosimetric description. Radiother Oncol. 2002;63:41–45. doi: 10.1016/S0167-8140(02)00061-0.
    1. Collett D. Modeling Survival Data in Meidcal Research. London: Chapman and Hall; 1994.
    1. Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJM, Nowak PCJM, et al. Stereotactic body radiation therapy for primary and metastatic liver tumros: A single intstitution phase I-II study. Acta Oncol. 2006;45:831–837. doi: 10.1080/02841860600897934.
    1. Hawkins M, Dawson L. Radiation therapy for hepatocellular carcinoma. Cancer. 2006;106:1653–1663. doi: 10.1002/cncr.21811.
    1. Chi KH, Liao CS, Chang CC, Ko HL, Tsang YW, Yang KC, et al. Angiogenic blockade and radiotherapy in hepatocellular cacrcinoma. IntJ Radiat Oncol Biol Phys. 2010;78(1):188–193. doi: 10.1016/j.ijrobp.2009.07.1725.
    1. Dawson LA, Brade A, Cho C, Kim J, Brierly R, Dinniwell R, et al. Phase 1 study of sorafenib and SBRT for advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012;84(supp l3):S10–S11. doi: 10.1016/j.ijrobp.2012.07.033.
    1. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, et al. Sunitib versus Sorafenib in advance hepatocellular carcinoma: result of a randomized phase III trial. J Clin Oncol. 2013;31(32):4067–4075. doi: 10.1200/JCO.2012.45.8372.
    1. Xi M, Zhang L, Zhao L, Li QQ, Guo SP, Feng ZZ, et al. Effectiveness of stereotactic body radiation therapy for hepatocellular carcinoma with portal vein and /or inferior vena cava tumor thrombosis. PLoS One. 2013;8(5) doi: 10.1371/journal.pone.0063864.
    1. Order SE, Stillwagon GB, Klein JL, Leichner PK, Siegelman SS, Fishman EK, et al. Iodine 131 antiferritin, a new treatment modality in hepatoma, a radiation therapy oncology group study. J Clin Oncol. 1985;13:1573–1582.
    1. Park HC, Seong J, Han KH, Chon CY, Monn YU, Suh CO. Dose-response relationship in local radiotherapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2002;54:150–155. doi: 10.1016/S0360-3016(02)02864-X.
    1. Park W, Lim do H, Paik SW, Koh KC, Choi MS, Park CK, et al. Local radiotherapy for patients with unresectable hepatocllular carcinoma. Int J Radiat Oncol Biol Phys. 2005;61:1143–1150. doi: 10.1016/j.ijrobp.2004.08.028.
    1. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–931. doi: 10.1056/NEJMoa1112824.
    1. Lee Y, Auh SL, Wang Y, Burnett B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8t T cells: Changing strategies for cancer treatment. Blood. 2009;114:589–595. doi: 10.1182/blood-2009-02-206870.
    1. Adler JR, Chang SD, Murphy MJ, Doty J, Gets P, Hancock SL. The Cyberknife: a frameless robotic system for radiosurgery. Stereotact Funct Neurosurg. 1997;69:124–128. doi: 10.1159/000099863.
    1. Huang WY, Jen YM, Lee MS, Chang LP, Chen CM, Ko KH, et al. Stereotactic body radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012;84(2):355–361. doi: 10.1016/j.ijrobp.2011.11.058.
    1. Janoray G, Chapel S, Ruffier-Loubiere A, Bernadou G, Pointreau Y, Calais G. Robotic stereotactic radiation therapy for tumors of the liver: radiation-induced liver disease, incidence and predictive factors. Cancer Radiother. 2014;18(3):191–197. doi: 10.1016/j.canrad.2014.03.009.
    1. Takeda A, Takahashi M, Kunieda E, Takeda T, Sanuki N, Koike Y, et al. Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: preliminary results for efficay and toxicity. Hepatol Res. 2008;38:60–69. doi: 10.1111/j.1872-034X.2007.00084.x.
    1. Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davis N, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 2007;30:6–25. doi: 10.1007/s00270-006-0062-3.
    1. Kasugi H, Osaki Y, Oka H, Kudo M, Seki T, Osaka Liver Cancer Group Severe complications of radiofrequency ablation therapy for hepatocellular carcinoma: An analysis of 3,891 ablations in 2,614 patients. Oncology. 2007;72:72–75. doi: 10.1159/000111710.

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