Frederika A van Nimwegen1, Michael Schaapveld1, Cecile P M Janus1, Augustinus D G Krol1, John M M Raemaekers1, Leontien C M Kremer1, Marilyn Stovall1, Berthe M P Aleman1, Flora E van Leeuwen2. 1. Frederika A. van Nimwegen, Michael Schaapveld, Berthe M.P. Aleman, and Flora E. van Leeuwen, The Netherlands Cancer Institute; Michael Schaapveld, Comprehensive Cancer Centre the Netherlands; Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam; Cecile P.M. Janus, Erasmus Medical Center Cancer Institute, Rotterdam; Augustinus D.G. Krol, Leiden University Medical Center, Leiden; John M.M. Raemaekers, Radboud University Medical Center, Nijmegen, and Rijnstate Hospital, Arnhem, the Netherlands; and Marilyn Stovall, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. Frederika A. van Nimwegen, Michael Schaapveld, Berthe M.P. Aleman, and Flora E. van Leeuwen, The Netherlands Cancer Institute; Michael Schaapveld, Comprehensive Cancer Centre the Netherlands; Leontien C.M. Kremer, Emma Children's Hospital/Academic Medical Center, Amsterdam; Cecile P.M. Janus, Erasmus Medical Center Cancer Institute, Rotterdam; Augustinus D.G. Krol, Leiden University Medical Center, Leiden; John M.M. Raemaekers, Radboud University Medical Center, Nijmegen, and Rijnstate Hospital, Arnhem, the Netherlands; and Marilyn Stovall, The University of Texas MD Anderson Cancer Center, Houston, TX. f.v.leeuwen@nki.nl.
Abstract
PURPOSE: Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. PATIENTS AND METHODS: Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. RESULTS: After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% 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). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P < .001). CONCLUSION: Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.
PURPOSE: Recently, an increased risk of diabetes mellitus (DM) was observed after abdominal irradiation for childhood cancer. Because many Hodgkin lymphoma (HL) survivors have also been treated with infradiaphragmatic radiotherapy, we evaluated the association between HL treatment and DM risk. PATIENTS AND METHODS: Our study cohort comprised 2,264 5-year HL survivors, diagnosed before age 51 years and treated between 1965 and 1995. Treatment and follow-up information was collected from medical records and general practitioners. Radiation dosimetry was performed to estimate radiation dose to the pancreas. Cumulative incidence of DM was estimated, and risk factors for DM were evaluated by using Cox regression. RESULTS: After a median follow-up of 21.5 years, 157 patients developed DM. Overall cumulative incidence of DM after 30 years was 8.3% (95% CI, 6.9% to 9.8%). After para-aortic radiation with ≥ 36 Gy, the 30-year cumulative incidence of DM was 14.2% (95% CI, 10.7% to 18.3%). Irradiation with ≥ 36 Gy to the para-aortic lymph nodes and spleen was associated with a 2.30-fold increased risk of DM (95% 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). Lower doses (10 to 35 Gy) did not significantly increase risk of DM. The risk of DM significantly increased with higher mean radiation doses to the pancreatic tail (P < .001). CONCLUSION: Radiation to the para-aortic lymph nodes increases the risk of developing DM in 5-year HL survivors. Screening for DM should be considered in follow-up guidelines for HL survivors, and treating physicians should be alert to this increased risk.
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