Radiogenic Second Cancer Risk Differences in Female Hodgkin Lymphoma Patients Treated with Proton versus Photon Radiotherapies
Date of Graduation
Doctor of Philosophy (PhD)
Wayne D. Newhauser, Ph.D.
Rebecca M. Howell, Ph.D.
Dragan Mirkovic, Ph.D.
Carol J. Etzel, Ph.D.
Anita Mahajan, M.D.
Hodgkin Lymphoma (HL) is the most common cancer diagnosis of young adults in the United States. Advances in curative treatments for HL, including the use of photon radiation therapy (RT) techniques, have increased 10 year survival rates to approximately 90% among young patients. These RT treatments, however, contribute to an increased incidence of radiogenic second cancer (RSC) formation to the healthy tissue surrounding the tumor volume relative to the general population. These RSCs are the leading cause of death among long-term HL survivors. Proton therapy has been shown to reduce the therapeutic dose, and therefore, the risk of developing a RSC, to healthy tissue relative to HL photon therapy. Current commercial treatment planning systems (TPS) do not account for stray radiation doses for these treatments, however. The impact of these contributions on RSC incidence was previously unknown.
The relative risk (RR) of developing a RSC following treatment with proton therapy compared to the current standard of care, photon intensity modulate radiation therapy (IMRT), was determined for the breast, lung, and thyroid (OARs) of nine HL patients. Treatment plans were developed and therapeutic doses were calculated with commercial TPSs. Stray dose contributions were measured with thermoluminescent dosimeters (TLD) in anthropomorphic phantom for the IMRT treatments and simulated using Monte Carlo techniques that model a passive scattering treatment nozzle and each individual patient’s anatomy and treatment setup. RSC risks were calculated using the Biological Effects of Ionizing Radiation VII (BEIR VII) and Radiation Risk Assessment Tool (RadRAT) risk models. Sensitivity tests varied the dose response model, relative biological effectiveness (RBE) of neutrons for carcinogenesis, age of exposure, and attained age for each patient to characterize the uncertainty of the RSC RR results.
The risk analysis showed that the majority of comparisons indicated a lower RSC risk after proton therapy than photon IMRT, but were not statistically significant unless the values of all patients for a given OAR were averaged together. Our findings, for the first time, revealed that it is important to include stray dose contributions and their uncertainties when comparing the RSC risks after different treatment techniques for HL. Furthermore, our findings clearly demonstrated the importance of personalized dose and risk calculations for modern radiotherapy for HL.
Second Cancer Risk, Proton Therapy, Hodgkin Lymphoma, Photon IMRT, Monte Carlo, Neutron Dose