Radiotherapy's forgotten organ: pancreatic toxicity in adult and pediatric populations.
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Radiotherapy to the upper abdomen exposes the pancreas to radiation, yet the pancreas is not considered a dose-limiting organ. Emerging evidence indicates that moderate-dose radiation can cause clinically significant pancreatic toxicity. This review synthesizes available data on radiation-induced pancreatic injury, focusing on volume changes, functional alterations, and underlying mechanisms. Available data show that radiotherapy exceeding a mean dose of 45 Gy is associated with a mean reduction in pancreatic volume of 31.81 cm3 at 1 year. In pediatric patients, the rate of glucose dysregulation reaches 41% at 10 years, with a 2.44-fold higher relative risk of diabetes beyond 20 years of follow-up; children aged ≤ 10 years appear particularly vulnerable. A mean dose ≥ 10 Gy EQD2 to the pancreatic tail increases diabetes risk by more than 11-fold in this population. Similarly, in adults, radiotherapy is associated with a pooled diabetes hazard ratio of 2.17, with a mean pancreatic dose ≥ 21 Gy EQD2 conferring substantially elevated risk. Radiobiological insights suggest that both direct β-cell injury and indirect vascular and stromal damage contribute to late pancreatic insufficiency. The current evidence is insufficient to definitively establish a robust dose-response relationship. However, recognizing the pancreas as a relevant organ at risk is an important step toward reducing long-term morbidity in cancer survivors.