Secondary cancer risk following radiotherapy is an increasingly important topic in clinical oncology with impact on treatment decision making and on patient management. Much of the evidence that underlies our understanding of secondary cancer risks and our risk estimates are derived from large epidemiologic studies and predictive models of earlier decades with large uncertainties. The modern era is characterized by more conformal radiotherapy technologies, molecular and genetic marker approaches, genome-wide studies and risk stratifications, and sophisticated biologically based predictive models of the carcinogenesis process. Four key areas that have strong evidence toward affecting secondary cancer risks are 1) the patient age at time of radiation treatment, 2) genetic risk factors, 3) the organ and tissue site receiving radiation, and 4) the dose and volume of tissue being irradiated by a particular radiation technology. This review attempts to summarize our current understanding on the impact on secondary cancer risks for each of these known risk factors. We review the recent advances in genetic studies and carcinogenesis models that are providing insight into the biologic processes that occur from tissue irradiation to the development of a secondary malignancy. Finally, we discuss current approaches toward minimizing the risk of radiation-associated secondary malignancies, an important goal of clinical radiation oncology.
Keywords: genetic biomarkers; radiation; radiation techniques; radiation toxicities; radiobiology modeling; second cancer risk; secondary carcinogenesis.