Pancreas-Tail Radiation Linked to Increased Diabetes Risk

By Will Boggs MD

August 06, 2019

NEW YORK (Reuters Health) - Radiation to the tail of the pancreas as part of childhood cancer treatment is associated with an increased risk of subsequent diabetes, according to findings from the Childhood Cancer Survivor Study (CCSS).

"These findings underscore the importance of careful lifelong surveillance, including glucose monitoring, in patients treated with abdominal radiation during childhood, especially among those diagnosed with pediatric malignancies at the youngest ages (i.e., younger than age five)," Dr. Danielle Novetsky Friedman from Memorial Sloan Kettering Cancer Center, in New York City, told Reuters Health by email.

Previous studies have demonstrated a relationship between diabetes risk and abdominal radiation in childhood-cancer survivors, but the exact nature of this relationship is uncertain.

Dr. Friedman and colleagues investigated the association between pancreatic radiation dose-volume and the risk of diabetes among more than 4,568 childhood-cancer survivors exposed to abdominal radiation, 16,194 survivors without such exposure and 4853 of their siblings.

Among childhood-cancer survivors treated with abdominal radiation, 2.3% reported diabetes at a median age of 30 years, compared with 1.2% of survivors not treated with abdominal radiation at a median age of 28 years. Among siblings, 0.8% reported diabetes at a median age of 34 years.

Survivors exposed to abdominal radiation were 2.92-fold more likely than siblings and 60% more likely than survivors not exposed to abdominal radiation to develop diabetes, both statistically significant risk increases, the researchers report in the Journal of the National Cancer Institute, online July 22.

In multivariable analysis, older attained age, higher BMI and higher mean pancreatic-tail radiation dose were independently associated with increased disease risk among those exposed to abdominal radiation.

Age at diagnosis modified this risk. Those diagnosed with cancer at <10 years of age were at increased risk for diabetes development with higher mean doses to the pancreatic tail, whereas those diagnosed at age 15 years or older were not at significantly increased risk for diabetes development at different mean pancreas-tail doses.

"Efforts are underway to design comprehensive risk prediction models that build on this work and incorporate demographic, treatment, and genetic factors to identify which childhood cancer survivors are at highest risk for the development of diabetes." Dr. Friedman said. "This work, which is also being conducted within the Childhood Cancer Survivor Study, will allow us to target high-risk survivors for future intervention studies."

Dr. Michael Schaapveld from the Netherlands Cancer Institute, in Amsterdam, who has studied the association between radiation therapy and diabetes, told Reuters Health by email, "Childhood-cancer survivors may already be at increased risk of cardiovascular diseases due to mediastinal irradiation or receipt of drugs such as cis- or carboplatin and doxo/epirubicin. Diabetes is yet another risk factor for cardiovascular diseases later in life and carries a risk of serious complications in itself."

"It seems worthwhile for patients to ask their general physician to check for (pre)diabetes at regular intervals from age 35-40 onwards and possibly to initiate treatment with oral glucose-lowering agents at lower thresholds," said Dr. Schaapveld, who was not involved in the new work.

"With regard to childhood cancer management, it is clear from several reports that the pancreas is sensitive to radiation damage, with higher doses giving more damage," he said. "Especially the pancreatic tail should be considered a critical structure and dose to the pancreatic tail should be constrained. If possible, irradiating the pancreatic tail should be avoided."

Dr. Florent de Vathaire from Institut Gustave Roussy, in Villejuif, France, who has reported a dose-response relation between radiation exposure of pancreas and subsequent risk of diabetes, said, "These results emphasize the need for radiation therapists to consider specifically the tail of the pancreas as, during childhood, an important organ at risk of complication and to modify, when possible, their treatment plans in order to avoid its irradiation. The tail of the pancreas has to be included (as an) organ at risk of complications in the guidelines for radiotherapy in onco-pediatrics."

"The concept of radiation-induced diabetes is an emerging entity, which has not been considered as a specific subtype and which has still to be characterized," Dr. de Vathaire, who also was not involved in the new study, told Reuters Health by email. "Another issue is to investigate the genetic susceptibility to radiation-induced diabetes."


J Natl Cancer Inst 2019.