title: Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures.
abstract: Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD. Patients and Methods The cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data. Results The median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91). Conclusion A significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Veerle A B
authors.initials: VA
authors.lastname: van den Bogaard
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Bastiaan D P
authors.initials: BD
authors.lastname: Ta
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Schaaf
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Angelique B
authors.initials: AB
authors.lastname: Bouma
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Astrid M H
authors.initials: AM
authors.lastname: Middag
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Enja J
authors.initials: EJ
authors.lastname: Bantema-Joppe
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Lisanne V
authors.initials: LV
authors.lastname: van Dijk
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Femke B J
authors.initials: FB
authors.lastname: van Dijk-Peters
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Laurens A W
authors.initials: LA
authors.lastname: Marteijn
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Gertruida H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Johannes G M
authors.initials: JG
authors.lastname: Burgerhof
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: John H
authors.initials: JH
authors.lastname: Maduro
authors.affiliation: All authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anne P G
authors.initials: AP
authors.lastname: Crijns
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000528:radiation effects*; D006352:Heart Ventricles / Q000528:radiation effects; D006801:Humans; D021621:Imaging, Three-Dimensional; D015994:Incidence; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D017202:Myocardial Ischemia / Q000401:mortality; D062645:Percutaneous Coronary Intervention / Q000706:statistics & numerical data; D011336:Probability; D016016:Proportional Hazards Models; D011829:Radiation Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D055815:Young Adult