Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study

Abstract

Background Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear. Methods Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided. Results Survivors exposed to abdRT (median age = 31.6 years, range = 10.2–58.3 years) were 2.92-fold more likely than siblings (95% confidence interval [CI] = 2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI = 1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RRper 10 years = 2.11, 95% CI = 1.70 to 2.62), higher body mass index (RRBMI 30+ = 5.00, 95% CI = 3.19 to 7.83 with referenceBMI 18.5–24.9), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (P < .001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk. Conclusions Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies

“…Also, HL patients required abdominal and cervical irradiation, yet we retrieved only TBI as a risk of hyperglycaemia development in our ALL cohort. Abdominal, cervical and cranial radiation did not appear to induce hyperglycaemia in our study, although this is contrary to findings in other studies which suggested the effect of abdominal radiation 30–32 . Strengths of our study include the large sample size of ALL patients, inclusion of risk factors for hyperglycaemia, complete patient records and numerous harmonized blood glucose data for ALL and NHL.…”

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer

“…RR leads to cancer relapse, poor treatment response, poor prognosis, decreased quality of life, and increased disease treatment burden. Furthermore, RR induces damage to canceradjacent normal tissues, disrupting the physiological and biochemical functions of normal tissue, resulting in symptoms, including radiation-related diarrhea, rectal bleeding, and radiation dermatitis [39][40][41] , as well as an increased risk of subsequent secondary cancer 26,[42][43][44] or chronic noncommunicable diseases including type II diabetes 45,46 or cardiovascular diseases 47 . Over the past century, to remove the barrier of RR, many studies have been carried out to investigate RR-related regulatory genes, molecules, and signaling pathways to uncover the underlying mechanisms of RR and to develop radiation sensitizers 48,49 .…”

Radioprotective Effects of Allium jesdianum Extract on Reduction of Pancrease Damages Following γ-Radiation through Down-regulation of Apoptotic Genes, Antioxidants Regulation, and Suppression of Inflammatory Markers

“…Reduced secretion of insulin is probably related to the destruction of β-cells following radiation (9). By the antioxidant feature, AJ appears to decrease blood glucose levels, thus affecting pancreatic beta cells.…”

“…In this pathologic condition, the occurrence of mutagenesis, altered number of Langerhans islets, and eventually, apoptosis are possible (8). In response to γ-ray exposure, diabetes occurs through impairment of insulin secretion (9). Recently, the mice exposed to a low dose of radiation (0.1 Gy) can disrupt the pancreatic cells (10).…”