Radiation to pancreas may increase risk for diabetes in childhood cancer survivors

Issue: September 2012

Little is known about the potential link between radiation exposure and diabetes. However, new data suggest that children and young adults treated with total body or abdominal radiation for childhood cancer may be at higher risk for diabetes.

Perspective from Mark A. Sperling, MD

Researchers conducted a retrospective cohort study by sending questionnaires to 3,468 survivors treated in eight centers throughout France and the United Kingdom from 1985 to 1995 for a solid cancer or lymphoma (excluding leukemia) during childhood. They obtained a response from 2,520 patients, with median follow-up of 30 years. Those who answered with a self-reported diabetes diagnosis were confirmed by the patients’ physician.

Florent de Vathaire, PhD, of the Centre for Epidemiology and Public Health (CESP) of INSERM at the Gustave Roussy Institute of France, and colleagues estimated the radiation dose received by the tail, head and body of the pancreas besides 185 other sites during the course of radiotherapy. The information was updated for French patients from 2008 to 2010.

Of the 2,520 patients, 1,078 (43%) underwent 30 years of follow-up, and 795 (74%) had received radiotherapy. According to data, 95 of the 2,520 patients (4%) who returned a questionnaire reported they had developed diabetes. Fifteen patients were not confirmed by a physician, and 15 were excluded due to the gestational diagnosis.

Of 65 patients with a confirmed diagnosis of diabetes, 58 (89%) were on medication; 12 (18%) used insulin only; 35 (54%) used oral medication only; and 11 (17%) used both, researchers wrote.

“The pancreas needs to be regarded as a critical organ when planning radiation therapy, particularly in children. Until now, the pancreas was one of the few organs not considered at risk of normal tissue complication in the French and UK national guidelines for cancer radiation therapy. Our findings indicate that the pancreas is an organ at risk during radiation therapy and has to be contoured when planning treatment, to ensure a radiation dose of as low as possible,” de Vathaire said in a press release.

The risk for diabetes increased significantly with radiation doses administered to the tail of the pancreas — in sites where islets of Langerhans were concentrated — up to 20 Gy to 29 Gy, the researchers wrote, adding that the risk reached a plateau for higher radiation doses. The estimated RR at 1 Gy was 1.61 (95% CI, 1.21-2.68).

There was no significant association between radiation dose and other parts of the pancreas, they wrote.

Compared with patients who did not undergo radiation, the RR for diabetes was high among those who received 10 Gy or more to the tail of the pancreas (RR=11.5; 95% CI, 3.9-34). Adjustments for BMI, age and sex did not change results (P<.0001).

Children aged younger than 2 years at the time of radiation were more sensitive to treatment compared with older patients (RR at 1 Gy=2.1; 95% CI, 1.4-4.3 vs. 1.4; 95% CI, 1.1-2.2). Moreover, researchers discovered a 16% incidence of diabetes in the 511 patients who received more than 10 Gy to the tail of the pancreas.

Further data demonstrated that 14.7% of patients who had been treated for neuroblastoma were diagnosed with diabetes by age 45 years compared with an average of 3.1% for other types of cancers, the researchers wrote.

In an accompanying editorial, Kevin C. Oeffinger, MD, of Memorial Sloan-Kettering Cancer Center, said, “The clinical implications of this study are important, since radiation remains an integral part of therapy for many children with Wilms’ tumor [a type of kidney cancer] or neuroblastoma. Diabetes is a major risk factor for all-cause and cardiovascular mortality.

“Further study is therefore needed to clarify the mechanisms underlying diabetes after abdominal radiation. Understanding these mechanisms will, hopefully, result in the development of targeted interventions that will lead to a reduction in risk in this population,” Oeffinger said.

For more information:

De Vathaire F. Lancet. 2012;doi:10.1016/S1470-2045(12)70323-6.
Oeffinger KC. Lancet. 2012;doi:10.1016/S1470-2045(12)70340-6.

Disclosure:

The researchers report no relevant financial disclosures.

Perspective

Mark A. Sperling, MD

Total body irradiation (TBI) in preparation for bone marrow transplantation in children is known to be associated with potential endocrine disorders, especially impairment of reproductive function (depending on the age of the subject and caution to shield the gonads), pituitary hypofunction, occasional precocious puberty, and thyroid abnormalities. Short stature may result from radiation to the spine and long bones making them resistant to growth hormone. These endocrine abnormalities are related to the dose administered and may appear years after the irradiation. However, diabetes mellitus has not been considered as a consequence of the radiation dose administered to the pancreas. The present study draws important attention to this possible association and clearly demonstrates a dose-response relation between the extent of radiation exposure of the pancreas and likelihood of developing a form of insulin-dependent diabetes. Those caring for children who are long-term survivors of cancer and experienced TBI will now be alerted to this possibility and educate parents and patients to the warning symptoms of increased urination, increased thirst, the recurrence of bed wetting and weight loss to enable earlier diagnosis and treatment. Diabetes is an additional concern and possible burden for cancer survivors, but a treatable one.

Mark A. Sperling, MD

Endocrine Today Editorial Board

Disclosures: Sperling reports no relevant financial disclosures.