Evaluation of Focal Liver Reaction After Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Dec 2

PMID 27907063

Citations 11

Authors

Shigeyuki Takamatsu

Kazutaka Yamamoto

Yoshikazu Maeda

Mariko Kawamura

Satoshi Shibata

Yoshitaka Sato

Kazuki Terashima

Yasuhiro Shimizu

Yuji Tameshige

Makoto Sasaki

Satoko Asahi

Tamaki Kondou

Satoshi Kobayashi

Osamu Matsui

Toshifumi Gabata

Affiliations

Soon will be listed here.

Abstract

Background: Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC.

Material And Methods: Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area.

Results: FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months.

Conclusion: This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

Citing Articles

Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma.

Zaki P, Chuong M, Schaub S, Lo S, Ibrahim M, Apisarnthanarax S Technol Cancer Res Treat. 2023; 22:15330338231206335.

PMID: 37908130 PMC: 10621304. DOI: 10.1177/15330338231206335.

Evaluation of Threshold Dose of Damaged Hepatic Tissue After Carbon-Ion Radiation Therapy Using Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging.

Ebara M, Shibuya K, Shimada H, Kawashima M, Hirasawa H, Taketomi-Takahashi A Adv Radiat Oncol. 2021; 6(6):100775.

PMID: 34934860 PMC: 8655403. DOI: 10.1016/j.adro.2021.100775.

Indicator for local recurrence of hepatocellular carcinoma after proton beam therapy: analysis of attenuation difference between the irradiated tumor and liver parenchyma on contrast enhancement CT.

Takahashi H, Sekino Y, Mori K, Okumura T, Nasu K, Fukuda K Br J Radiol. 2019; 93(1105):20190375.

PMID: 31670572 PMC: 6948081. DOI: 10.1259/bjr.20190375.

Inter-patient variations of radiation-induced normal-tissue changes in Gd-EOB-DTPA-enhanced hepatic MRI scans during fractionated proton therapy.

Richter C, Andronesi O, Borra R, Voigt F, Lock S, Duda D Clin Transl Radiat Oncol. 2019; 18:113-119.

PMID: 31341986 PMC: 6630151. DOI: 10.1016/j.ctro.2019.04.013.

Transient increases in serum α fetoprotein and protein induced by vitamin K antagonist II levels following proton therapy does not necessarily indicate progression of hepatocellular carcinoma.

Yoshida M, Ogino H, Iwata H, Hattori Y, Hashimoto S, Nakajima K Oncol Lett. 2019; 17(3):3026-3034.

PMID: 30854081 PMC: 6365914. DOI: 10.3892/ol.2019.9922.

References

Bland J, Altman D . Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986; 1(8476):307-10. View

Takeda A, Sanuki N, Eriguchi T, Kobayashi T, Iwabutchi S, Matsunaga K . Stereotactic ablative body radiotherapy for previously untreated solitary hepatocellular carcinoma. J Gastroenterol Hepatol. 2013; 29(2):372-9. DOI: 10.1111/jgh.12350. View

Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W . Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features. Radiology. 2010; 256(3):817-26. DOI: 10.1148/radiol.10092214. View

Richter C, Seco J, Hong T, Duda D, Bortfeld T . Radiation-induced changes in hepatocyte-specific Gd-EOB-DTPA enhanced MRI: potential mechanism. Med Hypotheses. 2014; 83(4):477-81. DOI: 10.1016/j.mehy.2014.08.004. View

Sanuki N, Takeda A, Oku Y, Eriguchi T, Nishimura S, Aoki Y . Threshold doses for focal liver reaction after stereotactic ablative body radiation therapy for small hepatocellular carcinoma depend on liver function: evaluation on magnetic resonance imaging with Gd-EOB-DTPA. Int J Radiat Oncol Biol Phys. 2014; 88(2):306-11. DOI: 10.1016/j.ijrobp.2013.10.045. View

Lee N, Kim S, Lee J, Lee S, Kang D, Kim G . Biliary MR imaging with Gd-EOB-DTPA and its clinical applications. Radiographics. 2009; 29(6):1707-24. DOI: 10.1148/rg.296095501. View

Seidensticker M, Seidensticker R, Mohnike K, Wybranski C, Kalinski T, Luess S . Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol. 2011; 6:40. PMC: 3090344. DOI: 10.1186/1748-717X-6-40. View

Olsen C, Welsh J, Kavanagh B, Franklin W, McCarter M, Cardenes H . Microscopic and macroscopic tumor and parenchymal effects of liver stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys. 2008; 73(5):1414-24. DOI: 10.1016/j.ijrobp.2008.07.032. View

Herfarth K, Hof H, Bahner M, Lohr F, Hoss A, Van Kaick G . Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys. 2003; 57(2):444-51. DOI: 10.1016/s0360-3016(03)00586-8. View

10.

Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider J . Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991; 21(1):109-22. DOI: 10.1016/0360-3016(91)90171-y. View

11.

Qi W, Fu S, Zhang Q, Guo X . Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis. Radiother Oncol. 2014; 114(3):289-95. DOI: 10.1016/j.radonc.2014.11.033. View

12.

Fowler J . Sensitivity analysis of parameters in linear-quadratic radiobiologic modeling. Int J Radiat Oncol Biol Phys. 2009; 73(5):1532-7. DOI: 10.1016/j.ijrobp.2008.11.039. View

13.

Son S, Jang H, Lee H, Choi B, Kang Y, Jang J . Determination of the α/β ratio for the normal liver on the basis of radiation-induced hepatic toxicities in patients with hepatocellular carcinoma. Radiat Oncol. 2013; 8:61. PMC: 3641977. DOI: 10.1186/1748-717X-8-61. View

14.

Ruhl R, Ludemann L, Czarnecka A, Streitparth F, Seidensticker M, Mohnike K . Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases. Radiat Oncol. 2010; 5:44. PMC: 2887889. DOI: 10.1186/1748-717X-5-44. View

15.

Kundel H, Polansky M . Measurement of observer agreement. Radiology. 2003; 228(2):303-8. DOI: 10.1148/radiol.2282011860. View

16.

DeLeve L, Shulman H, McDonald G . Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis. 2002; 22(1):27-42. DOI: 10.1055/s-2002-23204. View

17.

Haga J, Shimazu M, Wakabayashi G, Tanabe M, Kawachi S, Fuchimoto Y . Liver regeneration in donors and adult recipients after living donor liver transplantation. Liver Transpl. 2008; 14(12):1718-24. DOI: 10.1002/lt.21622. View

18.

Vander Borght S, Libbrecht L, Blokzijl H, Faber K, Moshage H, Aerts R . Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. J Pathol. 2005; 207(4):471-82. DOI: 10.1002/path.1852. View

19.

Yuan Y, Andronesi O, Bortfeld T, Richter C, Wolf R, Guimaraes A . Feasibility study of in vivo MRI based dosimetric verification of proton end-of-range for liver cancer patients. Radiother Oncol. 2013; 106(3):378-82. DOI: 10.1016/j.radonc.2013.01.016. View

20.

Nassif A, Jia J, Keiser M, Oswald S, Modess C, Nagel S . Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging. Radiology. 2012; 264(3):741-50. DOI: 10.1148/radiol.12112061. View