Researchers have uncovered evidence of a dose-response relation between radiation exposure of the pancreas and subsequent risk of diabetes mellitus in survivors of childhood cancers.
Although children and young adults who have undergone total body or abdominal radiotherapy have an increased risk of insulin resistance and diabetes, little is known about the effect of pancreas irradiation on this risk, noted Florent de Vathaire, PhD, of the Centre for Epidemiology and Public Health of INSERM at the Gustave Roussy Institute in Villejuif, France, and fellow investigators in their report for The Lancet Oncology. To learn more, the researchers reviewed responses from questionnaires they sent to 2,520 survivors of childhood cancer who had received treatment at eight centers throughout France and the United Kingdom between 1946 and 1985. Mathematical modeling techniques and information about how radiotherapy likely would have been delivered to a given patient allowed Vathaire’s team to reconstruct respondents’ radiation exposure.
The investigators validated 65 cases of diabetes by contacting the physicians of participants who reported having the disease. Overall, 6.6% of respondents who had undergone radiotherapy for childhood cancer had been diagnosed with diabetes by age 45 years, compared with 2.3% of respondents who had not received radiotherapy.
Diabetes risk increased strongly with radiation dose to the tail of the pancreas, where the islets of Langerhans are concentrated, up to 20-29 Grays (Gy), and then reached a plateau for higher radiation doses. Patients who the investigators determined to have received an average radiation dose of 24.2 Gy to the tail of the pancreas were 12.6 times more likely to be diagnosed with diabetes within 20 years after completing radiotherapy than were patients who did not receive radiotherapy. The cumulative incidence of diabetes was 16% for the 511 patients who had received more than 10 Gy to the tail of the pancreas. Radiation dose to the other parts of the pancreas did not have a significant effect.
Compared with patients who did not undergo radiotherapy, the relative risk of diabetes was 11.5. Adjustment for body-mass index (BMI) did not change the results, despite BMI having a strong independent effect on diabetes risk. The findings were similar between men and women.
The type of cancer for which a person received radiotherapy did affect future diabetes risk: 14.7% of patients with nephroblastoma had been diagnosed with diabetes by age 45 years, compared with an average of 3.1% of persons with other types of cancer included in the study.
Vathaire and associates advised that the pancreas be regarded as a critical organ when planning radiation therapy, particularly in children. Those who receive abdominal irradiation should undergo follow-up screening for diabetes.