title: Long-term cardiac mortality after hypofractionated radiation therapy in breast cancer.
abstract: OBJECTIVE
  To explore very-long-term mortality from ischemic heart disease (IHD) after locoregional radiation therapy of breast cancer (BC) in relation to degree of hypofractionation and other treatment variables.
  
  
  METHODS
  Two hypofractionated regimens used for locoregional radiation therapy for BC from 1975 to 1991 were considered. Patients received 4.3 Gy × 2/week (10 fractions; target dose 43 Gy; n=1107) or 2.5 Gy × 5/week (20 fractions; target dose 50 Gy; n=459). To estimate cardiac doses, radiation fields were reconstructed in a planning system. Time to death from IHD was the endpoint, comparing the groups with each other and with age-matched, cancer-free control individuals, modeled with the Cox proportional hazards model.
  
  
  RESULTS
  Patients given 4.3 Gy × 10 had an increased risk of dying of IHD compared with both the 2.5 Gy group (hazard ratio [HR] = 2.37; 95% confidence interval [CI]: 1.06-5.32; P=.036) and the control group (HR = 1.59; 95% CI: 1.13-2.23; P=.008). Photon beams for parasternal fields gave an increased risk of dying of IHD compared with electron beams (HR = 2.56; 95% CI: 1.12-5.84; P=.025). Multivariate analysis gave an increased risk for the 4.3-Gy versus 2.5-Gy regimen with borderline significance (HR = 2.90; 95% CI: 0.97-8.79; P=.057) but not for parasternal irradiation.
  
  
  CONCLUSIONS
  The degree of hypofractionation and parasternal photon beams contributed to increased cardiac mortality in this patient cohort. Differences emerged after 12 to 15 years, indicating the need of more studies with observation time of 2 decades.
authors.affiliation: Department of Oncology, Oslo University Hospital, National Resource Centre for Late Effects after Cancer Treatment, Oslo, Norway. krtjes@ous-hf.no
authors.forename: Kristin Holm
authors.initials: KH
authors.lastname: Tjessem
authors.forename: Safora
authors.initials: S
authors.lastname: Johansen
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
authors.forename: Kristin V
authors.initials: KV
authors.lastname: Reinertsen
authors.forename: Turi
authors.initials: T
authors.lastname: Danielsen
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
authors.forename: Alexander
authors.initials: A
authors.lastname: Fosså
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D004583:Electrons / Q000627:therapeutic use; D005260:Female; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000401:mortality*; D009664:Norway; D017785:Photons / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D013997:Time Factors; D055815:Young Adult