Para-Aortic Lymph Node Radiation Raises Risk of Developing Diabetes Mellitus in Hodgkin Lymphoma Survivors

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Radiation to the para-aortic lymph nodes, “leading to radiation exposure of the pancreas, is associated with a dose-dependent increased risk” of developing diabetes mellitus among long-term survivors of Hodgkin lymphoma (HL), according to a study by Frederika A. van Nimwegen,
, of the Netherlands Cancer Institute, Amsterdam, and colleagues.

“We found that the risk of [diabetes mellitus] is especially increased in patients who received a prescribed radiation dose of ≥ 36 Gy to the [para-aortic] fields or a mean radiation dose of ≥ 36 Gy to the pancreatic tail or whole pancreas,” the investigators reported in the Journal of Clinical Oncology. “Screening for [diabetes mellitus] should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk,” the researchers advised.

The study cohort comprised 2,264 patients who were diagnosed with HL before age 51 and survived at least 5 years after diagnosis. Patients were treated between 1965 and 1995 in five Dutch hospitals and cancer centers.

“Primary treatment was usually given according to treatment protocols of the European Organisation for Research and Treatment of Cancer,” the authors noted. In the 1960s and 1970s, patients usually received 40 Gy in fractions of 2.0 Gy when they were treated with radiotherapy only, and 30 to 36 Gy in fractions of 1.5 to 2.0 Gy when they also received chemotherapy. Infradiaphragmatic radiotherapy usually involving the para-aortic lymph nodes, “with or without the spleen/splenic hilum, but frequently also including the iliac and inguinal nodes, was given until the late 1980s as part of (sub)total nodal irradiation,” the investigators stated.

“After a median follow-up of 21.5 years, 157 patients developed [diabetes mellitus],” the researchers reported. The median age of those patients was 32.4 years during HL treatment and 53.9 years at diagnosis of diabetes mellitus. While the overall cumulative incidence of diabetes mellitus after 30 years was 8.3%, the incidence among patients who had received para-aortic radiation at ≥ 36 Gy was 14.2%.

“Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of [diabetes mellitus] [95% confidence interval (CI) = 1.54- to 3.44-fold] whereas para-aortic radiation alone with ≥ 36 Gy was associated with a 1.82-fold increased risk [95% CI = 1.02- to 3.25-fold],” according to the study report. Lower doses (10–35 Gy) did not significantly increase the risk of diabetes mellitus, but that risk significantly increased with higher mean radiation doses to the pancreatic tail (P < .001).

“The radiation-associated increased risk of [diabetes mellitus] was independent of the presence of obesity, which supports the results of previous studies,” the authors noted. “Only 8% of patients with [diabetes mellitus] were obese. A limitation of this study, however, is that the information on obesity status was obtained at end of follow-up and not at the time of [diabetes mellitus] diagnosis. Because patients may have lost weight after [diabetes mellitus] diagnosis, some misclassification may have occurred.”

While “radiotherapy to the spleen is rarely administered nowadays,” physicians should be aware of the increased risk of diabetes mellitus among long-term HL survivors who have received splenic or para-aortic irradiation as part of HL treatment in the past. “In addition, current patients with HL with (residual) upper abdominal disease as well as patients with testicular cancer or stomach cancer may still be exposed to radiation to the pancreas,” the authors noted.

“Early detection of [diabetes mellitus] may contribute to a substantial reduction of morbidity in long-term survivors of HL and may even reduce mortality by decreasing cardiovascular disease risk,” the researchers concluded. ■

van Nimwegen FA, et al: J Clin Oncol. August 25, 2014 (early release online).