Skip to main content
Top
Published in: Radiation Oncology 1/2013

Open Access 01-12-2013 | Research

Determination of the α/β ratio for the normal liver on the basis of radiation-induced hepatic toxicities in patients with hepatocellular carcinoma

Authors: Seok Hyun Son, Hong Seok Jang, Hyochun Lee, Byung Ock Choi, Young Nam Kang, Jeong Won Jang, Seung Kew Yoon, Chul Seung Kay

Published in: Radiation Oncology | Issue 1/2013

Login to get access

Abstract

Background

The purpose of this study was to determine the α/β ratio for normal liver with hepatitis by analyzing the toxicity data from patients with unresectable hepatocellular carcinoma treated with helical tomotherapy.

Methods

Between March 2006 and February 2012, 98 patients were eligible for this study. 66 patients received 45–50 Gy in 4.5-5 Gy fractions (Group A) and 32 patients received 36–60 Gy in 2.5-3 Gy fractions (Group B). Radiation-induced hepatic toxicity was defined as an increase of at least 2 points in the Child-Pugh score within 4 months of completing helical tomotherapy. We attempted to find the statistically significant parameters in the 2 groups using α/β ratios of 2, 4, 6, 8, or 10, and compared the estimated probability curves of each significant parameter. We hypothesized that the α/β ratio associated with the best matches for the curves between the 2 groups would be equivalent to the α/β ratio for the normal liver.

Results

When using an α/β ratio of 2 or 4, different parameters were found to be statistically significant in a multivariate analysis (Group A: VBED30 for α/β ratio = 2 and VBED25 for α/β ratio = 4, Group B: VBED25 for α/β ratio = 2 and VBED20 for α/β ratio = 4). When using an α/β ratio of 6, 8, or 10, VBED20 was found to be a statistically significant parameter in both groups. Comparison of the estimated probability curve of each significant parameter between the groups revealed that an α/β ratio of 8 resulted in the best matches.

Conclusions

We suggest that the α/β ratio of the normal liver with hepatitis is 8. We hope that previously reported parameters and their values can be effectively used in different fractionation schemes by calculating the biologically effective dose using an α/β ratio of 8.
Appendix
Available only for authorised users
Literature
1.
go back to reference Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K: Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985,56(4):918-928. 10.1002/1097-0142(19850815)56:4<918::AID-CNCR2820560437>3.0.CO;2-ECrossRefPubMed Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K: Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985,56(4):918-928. 10.1002/1097-0142(19850815)56:4<918::AID-CNCR2820560437>3.0.CO;2-ECrossRefPubMed
2.
go back to reference Kim TH, Kim DY, Park JW, Kim SH, Choi JI, Kim HB, Lee WJ, Park SJ, Hong EK, Kim CM: Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 2007,67(1):225-231. 10.1016/j.ijrobp.2006.08.015CrossRefPubMed Kim TH, Kim DY, Park JW, Kim SH, Choi JI, Kim HB, Lee WJ, Park SJ, Hong EK, Kim CM: Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys 2007,67(1):225-231. 10.1016/j.ijrobp.2006.08.015CrossRefPubMed
3.
go back to reference Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK: Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002,53(4):810-821. 10.1016/S0360-3016(02)02846-8CrossRefPubMed Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK: Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002,53(4):810-821. 10.1016/S0360-3016(02)02846-8CrossRefPubMed
4.
go back to reference Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, Yang YL, Chen L, Wang AY, Fu XL: 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 2006,65(2):426-434. 10.1016/j.ijrobp.2005.12.031CrossRefPubMed Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, Yang YL, Chen L, Wang AY, Fu XL: 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 2006,65(2):426-434. 10.1016/j.ijrobp.2005.12.031CrossRefPubMed
5.
go back to reference Liang S, Huang X, Zhu X, Zhang W, Cai L, Huang H, Li Y, Chen L, Liu M: Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis. Radiother Oncol 2011,98(2):265-269. 10.1016/j.radonc.2010.10.014CrossRefPubMed Liang S, Huang X, Zhu X, Zhang W, Cai L, Huang H, Li Y, Chen L, Liu M: Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis. Radiother Oncol 2011,98(2):265-269. 10.1016/j.radonc.2010.10.014CrossRefPubMed
6.
go back to reference Son SH, Choi BO, Ryu MR, Kang YN, Jang JS, Bae SH, Yoon SK, Choi IB, Kang KM, Jang HS: Stereotactic body radiotherapy for patients with unresectable primary hepatocellular carcinoma: dose-volumetric parameters predicting the hepatic complication. Int J Radiat Oncol Biol Phys 2010,78(4):1073-1080. 10.1016/j.ijrobp.2009.09.009CrossRefPubMed Son SH, Choi BO, Ryu MR, Kang YN, Jang JS, Bae SH, Yoon SK, Choi IB, Kang KM, Jang HS: Stereotactic body radiotherapy for patients with unresectable primary hepatocellular carcinoma: dose-volumetric parameters predicting the hepatic complication. Int J Radiat Oncol Biol Phys 2010,78(4):1073-1080. 10.1016/j.ijrobp.2009.09.009CrossRefPubMed
7.
go back to reference Lee IJ, Seong J, Shim SJ, Han KH: Radiotherapeutic parameters predictive of liver complications induced by liver tumor radiotherapy. Int J Radiat Oncol Biol Phys 2009,73(1):154-158. 10.1016/j.ijrobp.2008.04.035CrossRefPubMed Lee IJ, Seong J, Shim SJ, Han KH: Radiotherapeutic parameters predictive of liver complications induced by liver tumor radiotherapy. Int J Radiat Oncol Biol Phys 2009,73(1):154-158. 10.1016/j.ijrobp.2008.04.035CrossRefPubMed
8.
go back to reference Cheng JC, Wu JK, Huang CM, Liu HS, Huang DY, Cheng SH, Tsai SY, Jian JJ, Lin YM, Cheng TI: Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and implication. Int J Radiat Oncol Biol Phys 2002,54(1):156-162. 10.1016/S0360-3016(02)02915-2CrossRefPubMed Cheng JC, Wu JK, Huang CM, Liu HS, Huang DY, Cheng SH, Tsai SY, Jian JJ, Lin YM, Cheng TI: Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and implication. Int J Radiat Oncol Biol Phys 2002,54(1):156-162. 10.1016/S0360-3016(02)02915-2CrossRefPubMed
9.
go back to reference Dawson LA, Biersack M, Lockwood G, Eisbruch A, Lawrence TS, Ten Haken RK: Use of principal component analysis to evaluate the partial organ tolerance of normal tissues to radiation. Int J Radiat Oncol Biol Phys 2005,62(3):829-837. 10.1016/j.ijrobp.2004.11.013CrossRefPubMed Dawson LA, Biersack M, Lockwood G, Eisbruch A, Lawrence TS, Ten Haken RK: Use of principal component analysis to evaluate the partial organ tolerance of normal tissues to radiation. Int J Radiat Oncol Biol Phys 2005,62(3):829-837. 10.1016/j.ijrobp.2004.11.013CrossRefPubMed
10.
go back to reference Cheng J, Wu J, Lee P, Liu H, Jian J, Lin Y, Sung J, Jan G: Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease. Int J Radiat Oncol Biol Phys 2004, 60: 1502-1509. 10.1016/j.ijrobp.2004.05.048CrossRefPubMed Cheng J, Wu J, Lee P, Liu H, Jian J, Lin Y, Sung J, Jan G: Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease. Int J Radiat Oncol Biol Phys 2004, 60: 1502-1509. 10.1016/j.ijrobp.2004.05.048CrossRefPubMed
11.
go back to reference Son SH, Kay CS, Song JH, Lee SW, Choi BO, Kang YN, Jang JW, Yoon SK, Jang HS: Dosimetric parameter predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma. Radiat Oncol 2013, 8: 11. 10.1186/1748-717X-8-11CrossRefPubMedPubMedCentral Son SH, Kay CS, Song JH, Lee SW, Choi BO, Kang YN, Jang JW, Yoon SK, Jang HS: Dosimetric parameter predicting the deterioration of hepatic function after helical tomotherapy in patients with unresectable locally advanced hepatocellular carcinoma. Radiat Oncol 2013, 8: 11. 10.1186/1748-717X-8-11CrossRefPubMedPubMedCentral
12.
go back to reference Pan CC, Kavanagh BD, Dawson L, Li XA, Das SK, Miften M, Ten Haken RK: Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010,76(3):S94-S100. 10.1016/j.ijrobp.2009.06.092CrossRefPubMedPubMedCentral Pan CC, Kavanagh BD, Dawson L, Li XA, Das SK, Miften M, Ten Haken RK: Radiation-associated liver injury. Int J Radiat Oncol Biol Phys 2010,76(3):S94-S100. 10.1016/j.ijrobp.2009.06.092CrossRefPubMedPubMedCentral
13.
go back to reference Liaw Y, Sung JJ, Chow WC, Farrell G, Lee C, Yuen H, Tanwandee T, Tao Q, Shue K, Keene ON: Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004,351(15):1521-1531. 10.1056/NEJMoa033364CrossRefPubMed Liaw Y, Sung JJ, Chow WC, Farrell G, Lee C, Yuen H, Tanwandee T, Tao Q, Shue K, Keene ON: Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004,351(15):1521-1531. 10.1056/NEJMoa033364CrossRefPubMed
14.
go back to reference Cochrane AM, Murray-Lyon IM, Brinkley DM, Williams R: Quadruple chemotherapy versus radiotherapy in treatment of primary hepatocellular carcinoma. Cancer 1977,40(2):609-614. 10.1002/1097-0142(197708)40:2<609::AID-CNCR2820400203>3.0.CO;2-LCrossRefPubMed Cochrane AM, Murray-Lyon IM, Brinkley DM, Williams R: Quadruple chemotherapy versus radiotherapy in treatment of primary hepatocellular carcinoma. Cancer 1977,40(2):609-614. 10.1002/1097-0142(197708)40:2<609::AID-CNCR2820400203>3.0.CO;2-LCrossRefPubMed
15.
go back to reference Lewin K, Millis RR: Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol 1973,96(1):21-26.PubMed Lewin K, Millis RR: Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol 1973,96(1):21-26.PubMed
16.
go back to reference Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF: Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995,31(5):1237-1248. 10.1016/0360-3016(94)00418-KCrossRefPubMed Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF: Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995,31(5):1237-1248. 10.1016/0360-3016(94)00418-KCrossRefPubMed
17.
go back to reference Park W, Lim DH, Paik SW, Koh KC, Choi MS, Park CK, Yoo BC, Lee JE, Kang MK, Park YJ: Local radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2005,61(4):1143-1150. 10.1016/j.ijrobp.2004.08.028CrossRefPubMed Park W, Lim DH, Paik SW, Koh KC, Choi MS, Park CK, Yoo BC, Lee JE, Kang MK, Park YJ: Local radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2005,61(4):1143-1150. 10.1016/j.ijrobp.2004.08.028CrossRefPubMed
18.
go back to reference Seong J, Keum KC, Han KH, Lee DY, Lee JT, Chon CY, Moon YM, Suh CO, Kim GE: Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 1999,43(2):393-397. 10.1016/S0360-3016(98)00415-5CrossRefPubMed Seong J, Keum KC, Han KH, Lee DY, Lee JT, Chon CY, Moon YM, Suh CO, Kim GE: Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 1999,43(2):393-397. 10.1016/S0360-3016(98)00415-5CrossRefPubMed
19.
go back to reference Shim SJ, Seong J, Han KH, Chon CY, Suh CO, Lee JT: Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma. Liver Int 2005,25(6):1189-1196. 10.1111/j.1478-3231.2005.01170.xCrossRefPubMed Shim SJ, Seong J, Han KH, Chon CY, Suh CO, Lee JT: Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma. Liver Int 2005,25(6):1189-1196. 10.1111/j.1478-3231.2005.01170.xCrossRefPubMed
20.
go back to reference Ogata K, Hizawa K, Yoshida M, Kitamuro T, Akagi G, Kagawa K, Fukuda F: Hepatic injury following irradiation–a morphologic study. Tokushima J Exp Med 1963, 43: 240-251. Ogata K, Hizawa K, Yoshida M, Kitamuro T, Akagi G, Kagawa K, Fukuda F: Hepatic injury following irradiation–a morphologic study. Tokushima J Exp Med 1963, 43: 240-251.
Metadata
Title
Determination of the α/β ratio for the normal liver on the basis of radiation-induced hepatic toxicities in patients with hepatocellular carcinoma
Authors
Seok Hyun Son
Hong Seok Jang
Hyochun Lee
Byung Ock Choi
Young Nam Kang
Jeong Won Jang
Seung Kew Yoon
Chul Seung Kay
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2013
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-8-61

Other articles of this Issue 1/2013

Radiation Oncology 1/2013 Go to the issue