APBI: 27Gy in 5 Fractions for Early Breast Cancer

  • STATUS
    Recruiting
  • End date
    Jul 22, 2021
  • participants needed
    274
  • sponsor
    AHS Cancer Control Alberta
Updated on 22 January 2021
carcinoma
metastasis
ductal carcinoma in situ
axillary lymph node dissection
sentinel node
breast-conserving surgery
female breast cancer
ductal carcinoma
sentinel lymph node biopsy
partial breast irradiation

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.

Description

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: /=2 rather than /=3.4 as previously estimated. Radiobiologic modeling using /=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.

Details
Condition Breast Cancer, Breast Cancer Diagnosis, breast carcinoma, cancer, breast
Treatment APBI 27Gy in 5 fractions
Clinical Study IdentifierNCT02681107
SponsorAHS Cancer Control Alberta
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 50 yrs?
Are you female?
Do you have Breast Cancer?
Do you have any of these conditions: Breast Cancer or Breast Cancer Diagnosis or breast carcinoma or cancer, breast?
Female, with new invasive or in-situ ductal carcinoma of the breast
Treated with Breast conserving surgery (BCS) with negative margins
pN0 on sentinel node biopsy or axillary dissection; cN0 if DCIS alone
Maximum pathologic tumor diameter is 3.0 cm (invasive or DCIS)
No clinical or imaging evidence of distant metastases
Age 50 years or older at diagnosis
No contraindications to breast irradiation
Excellent or Good overall cosmetic score at baseline following BCS
Able and willing to provide written informed consent
Available for 2 year follow up at the treating RT centre

Exclusion Criteria

Age < 50 years at diagnosis
BRCA 1 or 2 pathogenic mutation
Pathologic tumor diameter >3cm (including DCIS+invasive disease)
Lobular histology alone
Triple negative (ER-, PR-, HER2-) or HER2 overexpressing disease
Margin (other than deep) <2 mm
Presence of both Grade 3 and lymphatic or vascular invasion
Fair or Poor overall cosmetic score at baseline following BCS
Presence of ipsilateral breast implants
Inability to develop an APBI plan meeting all dosimetry constraints
Unable to start RT within 16 weeks of BCS or 8 weeks of last iv chemotherapy
Unable or unwilling to sign informed consent document or attend for 2-year cosmetic assessment at the treating RT centre
Potential contraindications for breast RT including a confirmed diagnosis of lupus, scleroderma, or pregnancy
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