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

Abstract

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.

Figure 1

DVHs from the primary fields for in-field or partially in-field structures, normalized so that 95% of the PTV receives the prescribed dose of 60 Gy. DVHs for the CTV, PTV of the IMRT plan, right kidney, esophagus, non-tumor liver, stomach, left kidney and lungs are shown for the PBT (triangles) and IMRT (squares) plans.

Figure 2

Predicted dose distributions from the primary fields for IMRT (left) and PBT (right) in the axial (top), coronal (lower left) and sagittal (lower right) planes through isocenter. The contour marked in purple is for the CTV.

Figure 3

Site-specific predicted lifetime risks of SMN incidence after PBT and IMRT. Other solid SMN risks are based on the mean dose in the non-tumor body tissue. Leukemia risks are based on the mean dose in the red bone marrow.