title: Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer.
abstract: OBJECTIVE
  To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer.
  
  
  METHODS
  Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB. Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCT imaging.
  
  
  RESULTS
  All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (<0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose.
  
  
  CONCLUSIONS
  Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRT increased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.
authors.affiliation: Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK. ellen.donovan@icr.ac.uk
authors.forename: E M
authors.initials: EM
authors.lastname: Donovan
authors.forename: H
authors.initials: H
authors.lastname: James
authors.forename: M
authors.initials: M
authors.lastname: Bonora
authors.forename: J R
authors.initials: JR
authors.lastname: Yarnold
authors.forename: P M
authors.initials: PM
authors.lastname: Evans
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000532:radiotherapy*; D054893:Cone-Beam Computed Tomography; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000000981:diagnostic imaging / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000000981:diagnostic imaging / Q000453:epidemiology*; D009928:Organ Specificity; D019047:Phantoms, Imaging; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D013997:Time Factors