Medical Oncology

, Volume 28, Issue 4, pp 958–965 | Cite as

Undetectable late hepatic sequelae after hypofractionated stereotactic radiotherapy for liver tumors

  • Peter GunvénEmail author
  • Eduard Jonas
  • Henric Blomgren
  • Eva Rutkowska
  • Kristin Karlsson
  • Ingmar Lax
  • Seymour Levitt
Original paper


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.


Stereotactic body radiotherapy Radiosurgery Radiation injury Adverse effects Liver neoplasms Liver function tests Biliary tract 


Conflict of interest statement

No author has any conflicting interests.


  1. 1.
    Gunvén P, Blomgren H, Lax I, Levitt S. Curative stereotactic body radiotherapy for liver malignancy. Med Oncol. 2009;26:327–34.PubMedCrossRefGoogle Scholar
  2. 2.
    Dawson LA, Ten Haken RK. Partial volume tolerance of the liver to radiation. Semin Radiat Oncol. 2005;15:279–83.PubMedCrossRefGoogle Scholar
  3. 3.
    Emami B, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Pan CC, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedGoogle Scholar
  7. 7.
    Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med. 1980;104:584–8.PubMedGoogle Scholar
  8. 8.
    Lewin K, Millis RR. Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol. 1973;96:21–6.PubMedGoogle Scholar
  9. 9.
    Fajardo LF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol. 2005;44:13–22.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Eccles CL, et al. Change in diffusion weighted MRI during liver cancer radiotherapy: preliminary observations. Acta Oncol. 2009;48:1034–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Sindelar WF, Tepper J, Travis EL. Tolerance of bile duct to intraoperative irradiation. Surgery. 1982;92:533–40.PubMedGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    Sindelar WF, Hoekstra H, Restrepo C, Kinsella TJ. Pathological tissue changes following intraoperative radiotherapy. Am J Clin Oncol. 1986;9:504–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Cherqui D, et al. Common bile duct stricture as a late complication of upper abdominal radiotherapy. J Hepatol. 1994;20:693–7.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Gunvén P, Blomgren H, Lax I. Radiosurgery for recurring liver metastases after hepatectomy. Hepatogastroenterology. 2003;50:1201–4.PubMedGoogle Scholar
  22. 22.
    Lax I, Blomgren H, Larson D, et al. Extracranial stereotactic readiosurgery of localized targets. J Radiosurgery. 1998;1:135–48.CrossRefGoogle Scholar
  23. 23.
    Lax I, Blomgren H, Näslund I, Svanström R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33:677–83.PubMedCrossRefGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    Garcea G, Ong SL, Maddern GJ. Predicting liver failure following major hepatectomy. Dig Liver Dis. 2009;41:798–806.PubMedCrossRefGoogle Scholar
  28. 28.
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Hawkins RA, et al. Radionuclide evaluation of liver transplants. Semin Nucl Med. 1988;18:199–212.PubMedCrossRefGoogle Scholar
  31. 31.
    McGinty MP, Stewart RM, Fabian MJ, Fabian TC, Proctor KG. Gamma-scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis. Surgery. 1994;116:535–43.PubMedGoogle Scholar
  32. 32.
    Tagge EP, et al. Quantitative scintigraphy with deconvolutional analysis for the dynamic measurement of hepatic function. J Surg Res. 1987;42:605–12.PubMedCrossRefGoogle Scholar
  33. 33.
    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.PubMedGoogle Scholar
  34. 34.
    Zeman RK, et al. Tc-99 m HIDA scintigraphy in segmental biliary obstruction. J Nucl Med. 1981;22:456–8.PubMedGoogle Scholar
  35. 35.
    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.PubMedGoogle Scholar
  36. 36.
    Gupta S, Owshalimpur D, Cohen G, Margules R, Herrera N. Scintigraphic detection of segmental bile-duct obstruction. J Nucl Med. 1982;23:890–1.PubMedGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    Dawson LA, Eccles C, Craig T. Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol. 2006;45:856–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Peter Gunvén
    • 1
    Email author
  • Eduard Jonas
    • 2
  • Henric Blomgren
    • 1
  • Eva Rutkowska
    • 3
  • Kristin Karlsson
    • 4
  • Ingmar Lax
    • 4
  • Seymour Levitt
    • 5
    • 6
  1. 1.Department of OncologyRadiumhemmet, Karolinska University Hospital at SolnaStockholmSweden
  2. 2.Department of SurgeryDanderyds HospitalDanderydSweden
  3. 3.Directorate of Medical Imaging and RadiotherapyUniversity of LiverpoolLiverpoolUK
  4. 4.Department of Hospital PhysicsRadiumhemmet, Karolinska University Hospital at SolnaStockholmSweden
  5. 5.Department of OncologyRadiumhemmet, Karolinska University Hospital at SolnaStockholmSweden
  6. 6.Department of Therapeutic RadiologyUniversity of MinnesotaMinneapolisUSA

Personalised recommendations