The effect of radiation quality on the risks of second malignancies

Abstract Purpose: Numerous studies have implicated elevated second cancer risks as a result of radiation therapy. Our aim in this paper was to contribute to an understanding of the effects of radiation quality on second cancer risks. In particular, we developed a biologically motivated model to study the effects of linear energy transfer (LET) of charged particles (including protons, alpha particles and heavy ions Carbon and Neon) on the risk of second cancer.

A widely used approach to estimate the risk uses the so-called initiation-inactivation-repopulation model. Based on the available experimental data for the LET dependence of radiobiological parameters and mutation rate, we generalized this formulation to include the effects of radiation quality. We evaluated the secondary cancer risks for protons in the clinical range of LET, i.e., around 4-10 (KeV/μm), which lies in the plateau region of the Bragg peak.

For protons, at a fixed radiation dose, we showed that the increase in second cancer risks correlated directly with increasing values of LET to a certain point, and then decreased. Interestingly, we obtained a higher risk for proton LET of 10 KeV/μm compared to the lower LET of 4 KeV/μm in the low dose region. In the case of heavy ions, the risk was higher for Carbon ions than Neon ions (even though they have almost the same LET). We also compared protons and alpha particles with the same LET, and it was interesting to note that the second cancer risks were higher for protons compared to alpha particles in the low-dose region.

Overall, this study demonstrated the importance of including LET dependence in the estimation of second cancer risk. Our theoretical risk predictions were noticeably high; however, the biological end points should be tested experimentally for multiple treatment fields and to improve theoretical predictions.