Low-dose radiation and secondary malignancy: is there a causal relationship?

Radiography and computed tomography (CT) are important tools in cancer diagnosis, staging, and follow-up. More recently, the innovations in technology have allowed functional imaging of cancers with positron emission tomography (PET). The rapid advancement and utilization of imaging studies naturally involve an increase in exposure to ionizing radiation for patients and the concern for exposure-associated risks. Although magnetic resonance imaging (MRI) is used more often and does not expose patients to radiation, it often cannot replace CT or PET. In the Beyan et al study in this issue of Clinical Lymphoma & Myeloma, it is noted that the average radiation doses associated with diagnostic imaging studies in the follow-up care of patients with Hodgkin lymphoma at a median follow-up of approximately 15 months is between 0.85 Sv and 1.61 Sv. The article raises an important question: will low-dose radiation associated with imaging studies increase the risk of developing a secondary cancer? Data on atomic-bomb survivors have shown that a linear relationship exists between the development of cancer and dose from 0.1 Sv to approximately 2.5 Sv.1 In 1957, Gray introduced a concept that the incidence of radiation-induced leukemia follows a bell-shape curve because of the balance between the induction of transformed cells and cell killing.2 The balance between these 2 factors results in a curve that rises rapidly at low doses, plateaus, and falls steeply at high doses. Patients with Hodgkin lymphoma usually receive chemotherapy and/or radiation therapy, which are known to induce secondary cancers.3 Disentangling the contribution of low-dose radiation from imaging studies and other factors that might contribute to the development of secondary cancer is difficult and would require a relatively large number of patients. The Beyan et al study did not show the strength of the association of whether a cause-effect relationship truly exists between lowdose radiation and secondary cancer. A better approach to help answer the question is to use a carefully designed case-control study. Currently, there are no convincing data showing that radiologic imaging studies cause secondary cancer in patients with Hodgkin lymphoma. Patients with Hodgkin lymphoma are usually young and, therefore, might be more at risk for developing secondary cancer. Children are more sensitive to radiation-induced cancer than are adults by a factor of ≥ 10.4 Children also have a longer life expectancy, resulting in a larger window of opportunity for expressing radiation-induced cancer. Additionally, many cases of childhood cancer involve a germline mutation that might confer susceptibility to radiation-induced cancer. It has been demonstrated that children with Hodgkin lymphoma were more sensitive to the induction of breast cancer than children with other malignancies.5 In this light, the Beyan et al study reminds clinicians that the use of imaging studies should have clinical indications that benefit patients. There is also merit to informing patients of the potential risk that can occur from repeated low-dose exposure, especially in children.