title: Risk of diabetes mellitus in long-term survivors of Hodgkin lymphoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Frederika A
authors.initials: FA
authors.lastname: van Nimwegen
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.affiliation: 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.
authors.forename: Cecile P M
authors.initials: CP
authors.lastname: Janus
authors.affiliation: 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.
authors.forename: Augustinus D G
authors.initials: AD
authors.lastname: Krol
authors.affiliation: 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.
authors.forename: John M M
authors.initials: JM
authors.lastname: Raemaekers
authors.affiliation: 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.
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.affiliation: 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.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.affiliation: 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.
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.affiliation: 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.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D008198:Lymph Nodes / Q000528:radiation effects; D008297:Male; D010179:Pancreas / Q000528:radiation effects; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012307:Risk Factors; D017741:Survivors