title: Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines.
abstract: Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (Pdifference= .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (Ptrend< .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (Pinteraction= .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up.
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Frederika A
authors.initials: FA
authors.lastname: van Nimwegen
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Ntentas
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Darby
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.|Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Hauptmann
authors.affiliation: Department of Hematology, and.
authors.forename: Pieternella J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.affiliation: Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Cecile P M
authors.initials: CPM
authors.lastname: Janus
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Laurien
authors.initials: L
authors.lastname: Daniels
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Clinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.|Oxford Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cutter
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Berthe M P
authors.initials: BMP
authors.lastname: Aleman
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D017741:Survivors
chemical_list: D018943:Anthracyclines