The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities

Jenny Y Que, Li-Ching Lin, Kuei-Li Lin, Chia-Hui Lin, Yu-Wei Lin, Ching-Chieh Yang, Jenny Y Que, Li-Ching Lin, Kuei-Li Lin, Chia-Hui Lin, Yu-Wei Lin, Ching-Chieh Yang

Abstract

Background and aim: To evaluate the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other standard treatment option.

Methods: Between 2009 and 2011, 22 patients with unresectable huge HCC (≧10 cm) were treated with SBRT. dose ranged from 26 Gy to 40 Gy in five fractions. Overall survival (OS) and disease-progression free survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and toxicities were also assessed.

Results: After a median follow-up of 11.5 month (range 2-46 months). The objective response rate was achieved in 86.3% (complete response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2-46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose (p = 0.0017) were significant factors for survival. However, in multivariate analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child-Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild and well tolerated.

Conclusion: This study showed that SBRT can be delivered safely to huge HCC and achieved a substantial tumor regression and survival. The results suggest this technique should be considered a salvage treatment. However, local and regional recurrence remain the major cause of failure. Further studies of combination of SBRT and other treatment modalities may be reasonable.

Figures

Figure 1
Figure 1
The 1-yr local control rate and regional control rate from Cyberknife SBRT.
Figure 2
Figure 2
(A) Overall survival rate and (B) Disease progression-free survival rate from Cyberknife SBRT. The 1-yr. Overall survival rates and median survival time were 50% and 11 months, respectively. The 1 -yr. Disease progression-free survival rate and median disease-progression free survival rate were 31.8% and 6 months, respectively.

References

    1. Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Cutsem EV, Singh H, Chow WC, Ooi LL, Chow P, Khin MW, Koo WH. Management of hepatocellular carcinoma in Asia: consensus statement from the Asean Oncology summit 2009. Lancet Oncol. 2009;10:1111–1118. doi: 10.1016/S1470-2045(09)70241-4.
    1. Krishnan S, Dawson LA, Seong J, Akine Y, Beddar S, Briere TM, Crane CH, Mornex F. Radiotherapy for hepatocellular carcinoma: an overview. Ann Surg Oncol. 2008;15:1015–1024. doi: 10.1245/s10434-007-9729-5.
    1. Choi GH, Han DH, Kim DH, Choi SB, Kang CM, Kim KS, Choi JS, Park YN, Park JY, Kim DY, Han KH, Chon CY, Lee WJ. Outcome after curative resection for a huge (≥10 cm) hepatocellualr carcinoma and prognostic significance of gross tumor classification. Am J Surg. 2009;198(5):693–701. doi: 10.1016/j.amjsurg.2008.09.019.
    1. Pandey D, Lee KH, Wai CT, Wagholikar G, Tan KC. Long term outcome and prognostic factors for large hepatocellular carcinoma (10 cm or more) after surgical resection. Ann Surg Oncol. 2007;14:2817–2823. doi: 10.1245/s10434-007-9518-1.
    1. Yamashita Y, Taketomi A, Shirabe K, Aishima S, Tsuijita E, Morita K, Kayahima H, Maehara Y. Outcome of hepatic resection for huge hepatocellular carcinoma (≥10 cm in diameter) J Surg Oncol. 2011;104:292–298. doi: 10.1002/jso.21931.
    1. Liau KH, Ruo L, Shia J, Padela A, Gonen M, Jarnagin WR, Fong Y, D'Angelica MI, Blumgart LH, DeMatteo RP. Outcome of partial hepatectomy for large (≥10 cm) hepatocellular carcinoma. Cancer. 2005;104:1948–1955. doi: 10.1002/cncr.21415.
    1. Shah SS, Wei AC, Cleary SP, Yang I, McGilvray ID, Gallinger S, Grant DR, Greig PD. Prognosis and results after resection of very large (≥10 cm) hepatocellular carcinoma. J Gastrointest Surg. 2007;11:589–595. doi: 10.1007/s11605-007-0154-7.
    1. Maluccio A, Covey AM, Porat LB, Schubert J, Brody LA, Sofocleous CT, Getrajdman GI, Jarnagin W, Dematteo R, Blumgart LH, Fong Y, Brown KT. Transcatheter arterial embolization with only particle for treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2008;19:862–869. doi: 10.1016/j.jvir.2008.02.013.
    1. Llado L, Virgili J, Figueras J, Valls C, Dominguez J, Rafecas A, Torras J, Fabregat J, Guardiola J, Jaurrieta E. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial embolization. Cancer. 2000;88:50–57. doi: 10.1002/(SICI)1097-0142(20000101)88:1<50::AID-CNCR8>;2-I.
    1. Lee SG, Hwang S, Jung JP, Lee YJ, Kim KH, Ahn CS. Outcome of patients with huge hepatocellular carcinoma after primary resection and treatment of recurrent lesions. Br J Surg. 2007;94:320–326. doi: 10.1002/bjs.5622.
    1. Huang WY, Jen YM, Lee MS, Chang LP, Chen CM, Ko KS, Lin KT, Lin JC, Chao HL, Lin CS, Su YF, Fan CY, Chang YW. Stereotactic body radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012;84:355–361. doi: 10.1016/j.ijrobp.2011.11.058.
    1. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, Sherman M, Dawson LA. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26:657–664. doi: 10.1200/JCO.2007.14.3529.
    1. Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJM, Nowak P, Nuyttens JJ, Brandwijk RP, Verdoef C, Ijzermans J, Levendag PC. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I-II study. Acta Oncol. 2006;45:831–837. doi: 10.1080/02841860600897934.
    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, Pattynama PMT. 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. Shin YJ, Kim MS, Yoo SY, Chul KC, Seo YS, Kang JK, Park SC, Han CJ, Kim SB, Lee BH, Lee DH. Pilot study of stereotactic body radiotherapy for huge hepatocellular carcinoma unsuitable for other therapies. Tumori. 2010;96:65–70.
    1. Vautravers-Dewas C, Dewas S, Bonodeau F, Adenis A, Lacornerie T, Penel N, Lartigau E, Mirabel X. Image-guided robotic stereotactic body radiation therapy for liver metastases: is there a dose–response relationship? Int J Radiat Oncol Biol Phys. 2011;81:39–47.
    1. Park HC, Seong J, Han KH, Chon CY, Moon YM, Suh CO. Dose–response relationship in local radiotherapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2002;54:150–155.
    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. Hoogeman M, Prevost JB, Nuyttens J, Pöll J, Levendag P, Heijmen B. 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 LA, Li XA, Das SK, Miften M, Ten Haken RK. 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, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tome WA, Verellen D, Wang L, Yin FF. 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, Lee PC, Liu WS, Jen JM, Lin YM, Sung JL, Jan GJ. 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. Wulf J, Guckenberger M, Haedinger U, Oppitz U, Mueller G, Beier K, Flentje M. Stereotactic radiotherapy of primary liver cancer and hepatic metastases. Acta Oncol. 2006;45:838–847. doi: 10.1080/02841860600904821.
    1. Cheng JC, Wu JK, Huang CM, Huang CM, Cheng SH, Lin YM, Jian JJ, Yang PY, Chuang VP, Huang AT. 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. Cheng JC, Chuang VP, Cheng SH, Lin YM, Cheng TI, Yang PS, Jian JM, You DL, Horng CF, Huang AT. Unresectable hepatocellular carcinoma treated with radiotherapy and/or chemoembolization. Int J Cancer. 2001;96:243–252. doi: 10.1002/ijc.1022.
    1. Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH, Bae SH, Jung DH, Kim KB, Lee DH, Han CJ, Kim J, Park SC, Kim YH. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage therapy after incomplete transarterial chemoembolization. Cancer. 2012;118:5424–5431. doi: 10.1002/cncr.27533.
    1. Choi BY, Choi IB, Jang HS, Kang YN, Jang JS, Bae SH, Yoon SK, Chai GY, Kang KM. Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer. 2008;8:35. doi: 10.1186/1471-2407-8-35.
    1. Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106:1653–1663. doi: 10.1002/cncr.21811.
    1. Seong J, Park HC, Han KH, Chon CY. Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular carcinoma: a retrospective study of 158 patients. Int J Radiat Oncol Biol Phys. 2002;54:150–155.
    1. Park W, Lim DH, Palk SW, Koh KC, Choi MS, Park CK, Yoo BC, Lee JE, Kang MK, Park YJ, Nam HR, Ahn YC, Huh HJ. Local Radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2005;61:1143–1150. doi: 10.1016/j.ijrobp.2004.08.028.
    1. Dawson LA, McGinn CJ, Normolle D, Ten Haken RK, Walker S, Ensminger W, Lawrence TS. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies. J Clin Oncol. 2000;18:2210–2218.
    1. Seo YS, Kim MS, Yoo SY, Cho CK, Choi CW, Kim JH, Han CJ, Park SC, Lee BH, Kim YH, Lee DH. Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Oncol. 2010;102:209–214. doi: 10.1002/jso.21593.
    1. Rushoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigenberg, Chidel MA, Pugh TJ, Franklin W, Kane M, Gaspar LE, Schefter TE. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009;27:1572–1578. doi: 10.1200/JCO.2008.19.6329.
    1. Chang DT, Swaminath A, Kozak M, Weintraub J, Koong AC, Kim J, Dinniwell R, Brierley J, Kavanagh BD, Dawson LA, Schefter TE. Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. Cancer. 2011;117:4060–4069. doi: 10.1002/cncr.25997.
    1. Dunlap NE, Cai J, Biedermann GB, Yang W, Benedict ST, Ke S, Schefter TE, Kavanagh BD, Larner JM. Chest wall volume receiving >30 Gy predict risk of severe pain and or rib fracture after lung stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2010;76:796–801. doi: 10.1016/j.ijrobp.2009.02.027.

Source: PubMed

3
Se inscrever