Background: Previously, accelerated partial breast irradiation (APBI) using 3D conformal
      external beam techniques to deliver 38.5Gy in 10, twice daily, fractions caused worse
      fibrosis and cosmetic deterioration than standard whole breast irradiation (WBI) following
      breast conserving surgery (BCS) for women with early breast cancer. Over the decade since the
      original APBI technique was designed, long-term outcomes of various breast RT fractionation
      regimens have become available and suggest that normal tissue fibrosis and cosmesis varies
      with the radiobiological constant: α/β=2 rather than α/β=3.4 as previously estimated.
      Radiobiologic modeling using α/β=2, indicates that a dose of 27Gy in 5 daily treatments
      should result in comparable late effects as 42.5Gy in 16, or 50Gy in 25 fractions. This
      clinical trial will validate the safety of a short, convenient and less costly APBI using
      27Gy in 5 daily fractions.

      Objective: To determine the cosmetic and normal tissue outcomes of APBI using 3D-conformal RT
      with 27Gy in 5 fractions over 1 week.

      Methods: A single-arm, phase II, non-inferiority, prospective study will be conducted. 274
      women with newly diagnosed, invasive or in-situ ductal carcinoma treated with BCS and
      sentinel lymph node biopsy (or axillary dissection) who are candidates for WBI alone, will be
      treated. Subjects will be age 50 years and older, with tumors less than 3cm diameter, with
      negative margins and nodes and with excellent or good baseline cosmetic outcome following
      BCS. Patients with extensive ductal carcinoma in-situ, BRCA mutations, Grade 3 cancers with
      lymphatic or vascular invasion, or lobular carcinoma will be excluded. These selection
      criteria are similar to the Canadian RAPID trial. In the first phase of the study, 150
      patients will be recruited and interim analyses will be conducted to rule out unacceptable
      toxicity at 2 years.

      Study endpoints: The primary endpoint will be the proportion of women who retain an Excellent
      or Good cosmetic score at 2 years using the EORTC Cosmetic Rating System and clinical
      photographs taken prior to, and at 1 and 2 years after RT. Secondary endpoints will include
      rates and grades of breast fibrosis, induration, telangiectasia, breast pain, ipsilateral
      breast tumor recurrence, overall and breast cancer-specific survival and subsequent
      mastectomy rates.

      Sample size, statistical analyses: In the RAPID trial, 88% of patients with Excellent or Good
      cosmesis prior to RT had Excellent or Good scores at 3 years. Only patients with
      Excellent/Good cosmesis at baseline will be included in the current study. The proportion of
      women with Excellent/Good cosmesis at 1 and 2 years will be calculated. Using 80% power, a
      non-inferiority margin of 0.08 and a one-sided binomial test for non-inferiority and a
      significance level of 0.05, will require a sample size of 249 women with evaluable 2-yr
      cosmesis. 274 patients will be recruited to allow for a 10% drop-out rate. To ensure safety,
      a first interim analysis with Grade 2 or higher breast fibrosis as the primary endpoint, will
      be conducted when 50 patients have completed their 1-year assessment and repeated when 50
      patients have completed their 2-year follow up. If the rate of Grade 2 or higher fibrosis
      exceeds 5% at either time point, trial accrual will be suspended.

      Feasibility: Over 600 women eligible for this protocol receive RT in Alberta each year. If
      30% accept study participation, accrual will be complete in <2 years.