Diabetes in Childhood Cancer Survivors Linked to Radiation of Pancreas

A new study provides evidence that individuals whose pancreas was exposed to radiation during treatment of their childhood cancer have a higher risk of developing diabetes. The research, published in the Lancet, suggests the pancreas should be treated as a critical organ when planning and executing radiation therapy, especially in children. Florent de Vathaire, PhD, Radiation Epidemiology Group, Institut Gustave Roussy, and colleagues suggest patients should receive diabetes screening following radiation exposure to the abdomen.

Radiation to the tail of the pancreas is linked to an increased risk of diabetes in childhood cancer survivors

“Up to now, the pancreas did not exist in radiation therapy guidelines, because it was not supposed to be an organ at risk,” said de Vathaire. “We have shown that the pancreas is an organ at risk. As a consequence, radiation therapists should contour the pancreas when planning radiotherapy to lower the radiation dose to the pancreas.”

De Vathaire adds that the pediatricians and clinician in charge of long-term follow-up care guidelines need to screen childhood cancer survivors for diabetes after both abdominal and whole-body radiation therapy. Patients treated for left and bilateral nephroblastomas are at higher risk.

Study Design and Results

In a collaboration between the Institut Gustave Roussy and the University of Birmingham in the United Kingdom, a cohort study of 2,520 childhood cancer survivors was started in 1990. All participants were survivors of a childhood cancer treated at eight centers in France and the United Kingdom between 1946 and 1985. Participants filled out questionnaires and self-declared diabetes, which were confirmed by their doctors. Radiation doses based on treatment were estimated. “We investigated the relation between radiation dose to the pancreas and the risk of a subsequent diabetes diagnosis,” said de Vathaire.

The focus of the study on the correlation of diabetes and radiation dose received to the pancreas was spurred by several publications since 2005 showing a higher incidence of diabetes among childhood cancer survivors who had received abdominal or total body radiotherapy. “Up to now, no one study had investigated the relation between irradiation and the risk of diabetes,” said de Vathaire.

Of the 2,520 participants, 65 had late-onset diabetes. The risk of diabetes increased with radiation to the tail of the pancreas. The tail of the pancreas has a higher concentration of the islets of Langerhans. These cells are the insulin-producing cells of the pancreas. By age 45, 6.6% of patients treated with radiotherapy for a childhood malignancy had been diagnosed with diabetes, vs 2.3% for patients who had not received radiotherapy.

Higher doses of radiation resulted in a greater risk of developing diabetes later in life. Participants who had received more than 10 Gy of radiation to the tail of the pancreas were 11 times more likely to have diabetes than those who did not receive radiation. The effect was the same for both men and women. Those patients who received an average radiation dose of 24.2 Gy to the tail of the pancreas were 12 times more likely to have diabetes 20 years after their radiation therapy, compared to those who did not receive radiation therapy.

Radiation doses to other parts of the pancreas did not increase diabetes risk.

“I was quite surprised by the fact that we were able to show that the radiation dose to the tail of the pancreas was the important issue, and that, when controlling this dose, the radiation dose to other part of the pancreas did not play a role,” said de Vathaire.

Participants who were treated for nephroblatoma (Wilms tumor, this type of kidney cancer is common in children) had among the highest diabetes risk-14.7% of patients treated for this type of cancer had diabetes by age 45.

In an editorial accompanying the paper, Kevin Oeffinger, director of the program for adult survivors of pediatric cancer at Memorial Sloan-Kettering in New York, emphasized that the clinical implications of the study are important since “radiation remains an integral part of therapy for many children with Wilms tumor or neuroblastoma.” Oeffinger believes further studies need to clarify the mechanisms of diabetes risk from radiation therapy. The goal is development of new therapies that will minimize the diabetes risk.

Further studies on the risk of diabetes due to other types of radiation exposure-occupational exposure, CT scans, Chernobyl survivors, may provide further clarity. The link between genetic predisposition to diabetes and radiation exposure is important to investigate as well. The results could identify those patients who are at very high risk for diabetes induced by radiation exposure.

What can childhood cancer survivors do to help minimize their risk of diabetes? “It is very important for childhood cancer survivors to adopt a lifestyle lowering the risk of diabetes. This not only because of our results, but also because of what known about their risk of cardiovascular disease,” said de Vathaire.