Official Title
Accelerated Partial Breast Irradiation Using Five Daily Fractions: A Single Arm, Phase II, Prospective Cohort Study to Examine Cosmetic Outcomes and Toxicity (The ACCEL Trial)
Summary:
This study will test the safety of partial breast RT using 27Gy in 5 daily fractions which
is expected to be equally tolerated as standard whole breast irradiation (WBI) based on
radiobiologic modeling of the fibrosis response of normal tissues but be more convenient and
less costly than 3-6 weeks of standard WBI. 274 women will be treated. Rates of fibrosis and
cosmesis at 2 years will be compared to data already collected using standard WBI in the
Canadian RAPID trial.
Trial Description
Primary Outcome:
- Rate of Excellent or Good Global cosmetic score
Secondary Outcome:
- Breast induration
- Breast pain
- Local recurrence
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 tumours 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 tumour 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.
View this trial on ClinicalTrials.gov
