title: Radiation-induced cardiac toxicity after therapy for breast cancer: interaction between treatment era and follow-up duration.
abstract: OBJECTIVE
  Cardiac toxicity after breast radiotherapy (RT) has been widely described in "older" RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more "modern" RT trials have shown less cardiac toxicity. The comparisons between the "older" and "modern" trials are confounded by the longer follow-up time in the "older" trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT.
  
  
  METHODS
  The published data were surveyed using PubMed to identify studies using "breast cancer," "irradiation/radiotherapy," "cardiac/heart," and "toxicity/morbidity/mortality" in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as "older" (patient accrual start year before 1980) and "modern" (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up.
  
  
  RESULTS
  We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically <or=10 years and did not report an excess toxicity risk. The modern studies lacked longer follow-up.
  
  
  CONCLUSIONS
  Additional follow-up is needed to ensure that modern methods effectively reduce cardiac toxicity. Continued diligence to minimize cardiac exposure remains prudent.
authors.affiliation: Department of Radiation Oncology, Ege University School of Medicine, Izmir, Turkey.
authors.forename: Senem
authors.initials: S
authors.lastname: Demirci
authors.forename: Jiho
authors.initials: J
authors.lastname: Nam
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hubbs
authors.forename: Thu
authors.initials: T
authors.lastname: Nguyen
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Marks
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000528:radiation effects*; D006801:Humans; D011832:Radiation Injuries / Q000453:epidemiology* / Q000401:mortality; D013997:Time Factors