Risk of second malignant neoplasm following proton versus intensity-modulated photon radiotherapies for hepatocellular carcinoma

Phys Med Biol. 2010 Dec 7;55(23):7055-65. doi: 10.1088/0031-9155/55/23/S07. Epub 2010 Nov 12.


Hepatocellular carcinoma (HCC), the sixth most common cancer in the world, is a global health concern. Radiotherapy for HCC is uncommon, largely because of the likelihood of radiation-induced liver disease, an acute side effect that is often fatal. Proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) may offer HCC patients a better option for treating the diseased liver tissue while largely sparing the surrounding tissues, especially the non-tumor liver. However, even advanced radiotherapies carry a risk of late effects, including second malignant neoplasms (SMNs). It is unclear whether PBT or IMRT confers less risk of an SMN than the other. The purpose of this study was to compare the predicted risk of developing an SMN for a patient with HCC between PBT and IMRT. For both treatments, radiation doses in organs and tissues from primary radiation were determined using a treatment planning system; doses in organs and tissues from stray radiation from PBT were determined using Monte Carlo simulations and from IMRT using thermo-luminescent dosimeter measurements. Risk models of SMN incidence were taken from the literature. The predicted absolute lifetime attributable risks of SMN incidence were 11.4% after PBT and 19.2% after IMRT. The results of this study suggest that using proton beams instead of photon beams for radiotherapy may reduce the risk of SMN incidence for some HCC patients.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carcinoma, Hepatocellular / radiotherapy*
  • Humans
  • Liver Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Neoplasms, Radiation-Induced / etiology*
  • Organs at Risk / radiation effects
  • Photons / adverse effects*
  • Photons / therapeutic use
  • Proton Therapy
  • Protons / adverse effects*
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / adverse effects*
  • Risk Assessment


  • Protons