title: Risk of valvular heart disease after treatment for Hodgkin lymphoma.
abstract: BACKGROUND
  Hodgkin lymphoma (HL) survivors are at increased risk of developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response.
  
  
  METHODS
  A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided.
  
  
  RESULTS
  Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31-35, 36-40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02).
  
  
  CONCLUSIONS
  Radiation dose to the heart valves can increase the risk of clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up.
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: David J
authors.initials: DJ
authors.lastname: Cutter
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Darby
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Frederika A
authors.initials: FA
authors.lastname: van Nimwegen
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Augustinus D G
authors.initials: AD
authors.lastname: Krol
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Cecile P M
authors.initials: CP
authors.lastname: Janus
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA).
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK (DJC, SCD); Department of Psychosocial Research, Epidemiology and Biostatistics, the Netherlands Cancer Institute, Amsterdam, the Netherlands (MS, MH, FAvN, FEvL); Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands (ADGK); Department of Radiation Oncology, Erasmus Medical Center/Daniel den Hoed Clinic, Rotterdam, the Netherlands (CPMJ); Department of Radiation Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (BMPA). b.aleman@nki.nl.
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000528:radiation effects; D016022:Case-Control Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006349:Heart Valve Diseases / Q000209:etiology*; D006689:Hodgkin Disease / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000528:radiation effects; D016017:Odds Ratio; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013156:Splenectomy / Q000009:adverse effects*; D013997:Time Factors; D055815:Young Adult