Para-Aortic Lymph Node Radiation Increases Risk of Diabetes in Hodgkin Lymphoma Survivors


Key Points

  • Increased risk of diabetes was found in survivors who had received radiotherapy ≥ 36 Gy to the para-aortic lymph nodes, including or excluding the spleen, vs those receiving no para-aortic irradiation.
  • Patients receiving ≥ 36 Gy had a 2.58-fold greater risk of diabetes compared with the general population.

Abdominal irradiation for childhood cancer has been associated with increased risk of diabetes. In a Dutch study reported in the Journal of Clinical Oncology, van Nimwegen and colleagues assessed the relationship between infradiaphragm radiotherapy and risk of diabetes in long-term survivors of Hodgkin lymphoma, finding an increased risk in those receiving higher doses of radiation to the para-aortic lymph nodes, para-aortic lymph nodes and spleen, and pancreatic tail.

The study cohort consisted of 2,264 5-year survivors diagnosed before age 51 years and treated between 1965 and 1995 at five Dutch universities and cancer centers. Treatment and follow-up data were collected from medical records and general practitioners. Radiation doses to the pancreas were estimated by dosimetry.

Increased Risk

Median follow-up was 21.5 years. The overall 30-year cumulative incidence of diabetes was 8.3% (95% confidence interval [CI] = 6.9%–9.8%) among all patients, 6.1% (95% CI = 4.5%–8.0%) in those not receiving para-aortic radiation, 7.1% (95% CI = 4.2%­11.0%) in those who received 10 to 35 Gy to the para-aortic field, and 14.2% (95% CI = 10.7%­18.3%) in those receiving ≥ 36 Gy to the para-aortic field (P < .001).

On multivariate analysis, significantly increased risk of diabetes was observed with radiotherapy at ≥ 36 Gy to the para-aortic lymph nodes (hazard ratio [HR] = 2.28, P < .001, vs no para-aortic radiation), para-aortic lymph nodes and spleen (HR = 2.28, P < .001), and para-aortic lymph nodes without spleen (HR = 1.87, P = .017). Risk was also increased significantly in those with doses ≥ 36 Gy to the pancreatic tail (HR = 2.43, 95% CI = 1.22–4.85), which could reflect the high proportion of such patients also receiving radiation to the spleen.  

Comparison With General Population

Compared with the general population, risk of diabetes was increased among patients receiving ≥ 36 Gy to the para-aortic field (standardized incidence ratio [SIR] = 2.58, 95%CI = 1.74–3.68) but not among those receiving 10 to 35 Gy (SIR = 1.36). Patients treated with ≥ 36 Gy before age 25 years had a particularly elevated risk (SIR = 4.22, 95% CI = 2.18–7.36).

The investigators concluded: “Radiation to the para-aortic lymph nodes increases the risk of developing [diabetes mellitus] in 5-year [Hodgkin lymphoma] survivors. Screening for [diabetes mellitus] should be considered in follow-up guidelines for [Hodgkin lymphoma] survivors, and treating physicians should be alert to this increased risk.”

Flora E. van Leeuwen, PhD, of The Netherlands Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

The authors reported no conflicts of interest.

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