Skip to main content
Top
Published in: Medical Oncology 4/2011

01-12-2011 | Original paper

Undetectable late hepatic sequelae after hypofractionated stereotactic radiotherapy for liver tumors

Authors: Peter Gunvén, Eduard Jonas, Henric Blomgren, Eva Rutkowska, Kristin Karlsson, Ingmar Lax, Seymour Levitt

Published in: Medical Oncology | Issue 4/2011

Login to get access

Abstract

Hypofractionated liver stereotactic radiotherapy has produced long-term survival, but the hepatobiliary system is radiosensitive and may be severely damaged by the treatment. We have evaluated long-term radiation effects on hepatobiliary functions in the first long-term survivors reported after radiotherapy to the hepatobiliary system for liver tumors. Eleven patients were followed for up to 13 years after treatment of tumors ≤9 cm in size. Conventional blood chemistry, clearance of indocyanine green and segmental uptake and excretion of radiolabeled mebrofenin were assayed. Slightly abnormal routine blood chemistry was found during the first 2 years in some patients with pre-existing liver damage. Other parameters were seemingly unaffected, and liver segments which received differing mean doses did not differ measurably with regard to parenchymal or ductal function. Late liver functions were therefore not demonstrably affected by the radiotherapy in most patients even in the presence of mild cirrhosis, after previous exposure to liver toxic agents, or after resection. However, slight to moderate late dysfunction occurred in one patient after three courses of irradiation, and in a cirrhotic patient after two major liver resections following radiotherapy. Our previous doses for irradiation of liver tumors gave no measurable chronic side effects and may be increased in order to control tumors more effectively. In selected patients, irradiation is possible even in the presence of liver dysfunction, and previous irradiation or resection does not absolutely contraindicate salvage treatment by re-irradiation or resection.
Literature
1.
go back to reference Gunvén P, Blomgren H, Lax I, Levitt S. Curative stereotactic body radiotherapy for liver malignancy. Med Oncol. 2009;26:327–34.PubMedCrossRef Gunvén P, Blomgren H, Lax I, Levitt S. Curative stereotactic body radiotherapy for liver malignancy. Med Oncol. 2009;26:327–34.PubMedCrossRef
2.
go back to reference Dawson LA, Ten Haken RK. Partial volume tolerance of the liver to radiation. Semin Radiat Oncol. 2005;15:279–83.PubMedCrossRef Dawson LA, Ten Haken RK. Partial volume tolerance of the liver to radiation. Semin Radiat Oncol. 2005;15:279–83.PubMedCrossRef
3.
go back to reference Emami B, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMed Emami B, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMed
4.
go back to reference Blomgren H, Lax I, Näslund I, Svanström R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995;34:861–70.PubMedCrossRef Blomgren H, Lax I, Näslund I, Svanström R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995;34:861–70.PubMedCrossRef
5.
go back to reference Pan CC, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.PubMedCrossRef Pan CC, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.PubMedCrossRef
6.
go back to reference Reed GB Jr, Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 1966;48:597–611.PubMed Reed GB Jr, Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 1966;48:597–611.PubMed
7.
go back to reference Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med. 1980;104:584–8.PubMed Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med. 1980;104:584–8.PubMed
8.
go back to reference Lewin K, Millis RR. Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol. 1973;96:21–6.PubMed Lewin K, Millis RR. Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol. 1973;96:21–6.PubMed
9.
go back to reference Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol. 2005;44:13–22.PubMedCrossRef Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol. 2005;44:13–22.PubMedCrossRef
10.
go back to reference Cromheecke M, Grond AJ, Szabo BG, Hoekstra HJ. Short- and long-term histopathological changes in the canine liver following single high-dose intraoperative radiation therapy (IORT). Int J Radiat Biol. 1999;75:1437–48.PubMedCrossRef Cromheecke M, Grond AJ, Szabo BG, Hoekstra HJ. Short- and long-term histopathological changes in the canine liver following single high-dose intraoperative radiation therapy (IORT). Int J Radiat Biol. 1999;75:1437–48.PubMedCrossRef
11.
go back to reference Cromheecke M, et al. Tissue damage after single high-dose intraoperative irradiation of the canine liver: evaluation in time by means of radionuclide imaging and light microscopy. Radiat Res. 2000;154:537–46.PubMedCrossRef Cromheecke M, et al. Tissue damage after single high-dose intraoperative irradiation of the canine liver: evaluation in time by means of radionuclide imaging and light microscopy. Radiat Res. 2000;154:537–46.PubMedCrossRef
12.
go back to reference Herfarth KK, et al. Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys. 2003;57:444–51.PubMedCrossRef Herfarth KK, et al. Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys. 2003;57:444–51.PubMedCrossRef
13.
go back to reference Krix M, et al. Monitoring of liver metastases after stereotactic radiotherapy using low-MI contrast-enhanced ultrasound—initial results. Eur Radiol. 2005;15:677–84.PubMedCrossRef Krix M, et al. Monitoring of liver metastases after stereotactic radiotherapy using low-MI contrast-enhanced ultrasound—initial results. Eur Radiol. 2005;15:677–84.PubMedCrossRef
14.
go back to reference Eccles CL, et al. Change in diffusion weighted MRI during liver cancer radiotherapy: preliminary observations. Acta Oncol. 2009;48:1034–43.PubMedCrossRef Eccles CL, et al. Change in diffusion weighted MRI during liver cancer radiotherapy: preliminary observations. Acta Oncol. 2009;48:1034–43.PubMedCrossRef
15.
go back to reference Sindelar WF, Tepper J, Travis EL. Tolerance of bile duct to intraoperative irradiation. Surgery. 1982;92:533–40.PubMed Sindelar WF, Tepper J, Travis EL. Tolerance of bile duct to intraoperative irradiation. Surgery. 1982;92:533–40.PubMed
16.
go back to reference Brambs HJ, et al. Radiation sensitivity of the normal bile duct during high dose rate afterloading irradiation with Iridium 192. Experimental studies in pigs (in German). Strahlenther Onkol. 1993;169:721–8.PubMed Brambs HJ, et al. Radiation sensitivity of the normal bile duct during high dose rate afterloading irradiation with Iridium 192. Experimental studies in pigs (in German). Strahlenther Onkol. 1993;169:721–8.PubMed
17.
go back to reference Sindelar WF, Hoekstra H, Restrepo C, Kinsella TJ. Pathological tissue changes following intraoperative radiotherapy. Am J Clin Oncol. 1986;9:504–9.PubMedCrossRef Sindelar WF, Hoekstra H, Restrepo C, Kinsella TJ. Pathological tissue changes following intraoperative radiotherapy. Am J Clin Oncol. 1986;9:504–9.PubMedCrossRef
18.
go back to reference Cherqui D, et al. Common bile duct stricture as a late complication of upper abdominal radiotherapy. J Hepatol. 1994;20:693–7.PubMedCrossRef Cherqui D, et al. Common bile duct stricture as a late complication of upper abdominal radiotherapy. J Hepatol. 1994;20:693–7.PubMedCrossRef
19.
go back to reference Halevy A, Adam A, Stamp G, Benjamin IS, Blumgart LH. Radiation stricture of the biliary ducts: an emerging new entity? HPB Surg. 1992;5:267–70.PubMedCrossRef Halevy A, Adam A, Stamp G, Benjamin IS, Blumgart LH. Radiation stricture of the biliary ducts: an emerging new entity? HPB Surg. 1992;5:267–70.PubMedCrossRef
20.
go back to reference Mitsunaga S, et al. Extrahepatic portal vein occlusion without recurrence after pancreaticoduodenectomy and intraoperative radiation therapy. Int J Radiat Oncol Biol Phys. 2006;64:730–5.PubMedCrossRef Mitsunaga S, et al. Extrahepatic portal vein occlusion without recurrence after pancreaticoduodenectomy and intraoperative radiation therapy. Int J Radiat Oncol Biol Phys. 2006;64:730–5.PubMedCrossRef
21.
go back to reference Gunvén P, Blomgren H, Lax I. Radiosurgery for recurring liver metastases after hepatectomy. Hepatogastroenterology. 2003;50:1201–4.PubMed Gunvén P, Blomgren H, Lax I. Radiosurgery for recurring liver metastases after hepatectomy. Hepatogastroenterology. 2003;50:1201–4.PubMed
22.
go back to reference Lax I, Blomgren H, Larson D, et al. Extracranial stereotactic readiosurgery of localized targets. J Radiosurgery. 1998;1:135–48.CrossRef Lax I, Blomgren H, Larson D, et al. Extracranial stereotactic readiosurgery of localized targets. J Radiosurgery. 1998;1:135–48.CrossRef
23.
go back to reference Lax I, Blomgren H, Näslund I, Svanström R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33:677–83.PubMedCrossRef Lax I, Blomgren H, Näslund I, Svanström R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33:677–83.PubMedCrossRef
24.
go back to reference Steel G. Dose fractionation in radiotherapy. In: Mayles P, Nahum AE, Rosenwald J, editors. Handbook of radiotherapy physics. London: Taylor & Francis; 2007. p. 163–78.CrossRef Steel G. Dose fractionation in radiotherapy. In: Mayles P, Nahum AE, Rosenwald J, editors. Handbook of radiotherapy physics. London: Taylor & Francis; 2007. p. 163–78.CrossRef
25.
go back to reference Dawson LA, et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53:810–21.PubMedCrossRef Dawson LA, et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53:810–21.PubMedCrossRef
26.
go back to reference Jonas E, et al. Measurement of parenchymal function and bile duct flow in primary sclerosing cholangitis using dynamic 99 mTc-HIDA SPECT. J Gastroenterol Hepatol. 2006;21:674–81.PubMedCrossRef Jonas E, et al. Measurement of parenchymal function and bile duct flow in primary sclerosing cholangitis using dynamic 99 mTc-HIDA SPECT. J Gastroenterol Hepatol. 2006;21:674–81.PubMedCrossRef
27.
go back to reference Garcea G, Ong SL, Maddern GJ. Predicting liver failure following major hepatectomy. Dig Liver Dis. 2009;41:798–806.PubMedCrossRef Garcea G, Ong SL, Maddern GJ. Predicting liver failure following major hepatectomy. Dig Liver Dis. 2009;41:798–806.PubMedCrossRef
29.
go back to reference Ekman M, Fjälling M, Friman S, Carlson S, Volkman R. Liver uptake function measured by IODIDA clearance rate in liver transplant patients and healthy volunteers. Nucl Med Commun. 1996;17:235–42.PubMedCrossRef Ekman M, Fjälling M, Friman S, Carlson S, Volkman R. Liver uptake function measured by IODIDA clearance rate in liver transplant patients and healthy volunteers. Nucl Med Commun. 1996;17:235–42.PubMedCrossRef
30.
go back to reference Hawkins RA, et al. Radionuclide evaluation of liver transplants. Semin Nucl Med. 1988;18:199–212.PubMedCrossRef Hawkins RA, et al. Radionuclide evaluation of liver transplants. Semin Nucl Med. 1988;18:199–212.PubMedCrossRef
31.
go back to reference McGinty MP, Stewart RM, Fabian MJ, Fabian TC, Proctor KG. Gamma-scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis. Surgery. 1994;116:535–43.PubMed McGinty MP, Stewart RM, Fabian MJ, Fabian TC, Proctor KG. Gamma-scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis. Surgery. 1994;116:535–43.PubMed
32.
go back to reference Tagge EP, et al. Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function. J Surg Res. 1987;42:605–12.PubMedCrossRef Tagge EP, et al. Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function. J Surg Res. 1987;42:605–12.PubMedCrossRef
33.
go back to reference Brown PH, Juni JE, Lieberman DA, Krishnamurthy GT. Hepatocyte versus biliary disease: a distinction by deconvolutional analysis of technetium-99 m IDA time-activity curves. J Nucl Med. 1988;29:623–30.PubMed Brown PH, Juni JE, Lieberman DA, Krishnamurthy GT. Hepatocyte versus biliary disease: a distinction by deconvolutional analysis of technetium-99 m IDA time-activity curves. J Nucl Med. 1988;29:623–30.PubMed
34.
go back to reference Zeman RK, et al. Tc-99 m HIDA scintigraphy in segmental biliary obstruction. J Nucl Med. 1981;22:456–8.PubMed Zeman RK, et al. Tc-99 m HIDA scintigraphy in segmental biliary obstruction. J Nucl Med. 1981;22:456–8.PubMed
35.
go back to reference Yeh SH, et al. Technetium-99 m HIDA hepatic lobar distribution and retention ratios in detection of intrahepatic lithiasis. J Nucl Med. 1985;26:241–9.PubMed Yeh SH, et al. Technetium-99 m HIDA hepatic lobar distribution and retention ratios in detection of intrahepatic lithiasis. J Nucl Med. 1985;26:241–9.PubMed
36.
go back to reference Gupta S, Owshalimpur D, Cohen G, Margules R, Herrera N. Scintigraphic detection of segmental bile-duct obstruction. J Nucl Med. 1982;23:890–1.PubMed Gupta S, Owshalimpur D, Cohen G, Margules R, Herrera N. Scintigraphic detection of segmental bile-duct obstruction. J Nucl Med. 1982;23:890–1.PubMed
37.
go back to reference Aburano T, et al. Discordant hepatic uptake of Tc-99m HIDA and Tc-99m colloid in a patient with segmental biliary obstruction. Clin Nucl Med. 1988;13:599–601.PubMedCrossRef Aburano T, et al. Discordant hepatic uptake of Tc-99m HIDA and Tc-99m colloid in a patient with segmental biliary obstruction. Clin Nucl Med. 1988;13:599–601.PubMedCrossRef
38.
go back to reference Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol. 2006;45:856–64.PubMedCrossRef Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol. 2006;45:856–64.PubMedCrossRef
Metadata
Title
Undetectable late hepatic sequelae after hypofractionated stereotactic radiotherapy for liver tumors
Authors
Peter Gunvén
Eduard Jonas
Henric Blomgren
Eva Rutkowska
Kristin Karlsson
Ingmar Lax
Seymour Levitt
Publication date
01-12-2011
Publisher
Springer US
Published in
Medical Oncology / Issue 4/2011
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9567-3

Other articles of this Issue 4/2011

Medical Oncology 4/2011 Go to the issue