A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- Standard fractionation whole breast irradiation
- Conditions
- Breast Cancer
- Sponsor
- Radiation Therapy Oncology Group
- Enrollment
- 2354
- Locations
- 807
- Primary Endpoint
- Percentage of Participants With In-breast Recurrence (Local Failure)
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as effective as standard per daily radiation therapy in treating breast cancer.
PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per daily radiation therapy with concomitant boost works compared to standard per daily radiation therapy with a sequential boost in treating patients with early-stage breast cancer that was removed by surgery.
Detailed Description
OBJECTIVES: Primary * To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients. Secondary * To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost. * To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and normal tissue complication probability (NTCP) calculations. * To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity. * To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost. * To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI. * If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients. * To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost. OUTLINE: This is a multicenter study. Patients are stratified according to age (\< 50 vs. ≥ 50 years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within 9 weeks of last surgery or chemotherapy delivery. After completion of study therapy, patients are followed at 1 month, at 6 months, and then yearly.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole breast irradiation with boost without regional nodal irradiation planned
- •The patient must be female
- •The patient must meet at least one of the three following criteria:
- •A. Pathological stage I, II Breast Cancer AND at least one of the following:
- •Age \< 50 years or
- •Positive axillary nodes or
- •Lymphovascular space invasion or
- •2 or more close resection margins (\> 0 mm to ≤ 2 mm) or
- •1 close resection margin and extensive intraductal component (EIC) \[Per College of American Pathologist (CAP) Recommendation\] or
- •Focally positive resection margins or
Exclusion Criteria
- •American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, M1 pathologic stages III or IV breast cancer
- •Treatment plan that includes regional node irradiation
- •Prior invasive non-breast malignancy (except non-melanomatous skin cancer, carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
- •Prior invasive or in-situ carcinoma of the breast \[-prior lobular carcinoma in situ (LCIS) is eligible\]
- •Two or more breast cancers not resectable through a single lumpectomy incision
- •Bilateral breast cancer
- •DCIS only (without an invasive component) and age ≥ 50 years
- •DCIS nuclear grade 1 or 2 only (without an invasive component) and age \< 50 years
- •Invasive breast cancer and low risk for 5-year in breast recurrence after lumpectomy with negative margins that does not meet one of the eligibility factors in 3.1.
- •Unable to delineate on CT scan the extent of the target lumpectomy cavity for boost (Placement of surgical clips to assist in treatment planning of the boost is strongly recommended, see Section 6.4.2 for details)
Arms & Interventions
Whole breast irradiation + sequential boost
Standard fractionation whole breast irradiation (WBI) with sequential boost.
Intervention: Standard fractionation whole breast irradiation
Whole breast irradiation + sequential boost
Standard fractionation whole breast irradiation (WBI) with sequential boost.
Intervention: Sequential boost
Hypofractionated whole breast irradiation + concurrent boost
Hypofractionated whole breast (H-WBI) irradiation with a concurrent boost
Intervention: Hypofractionated whole breast irradiation
Hypofractionated whole breast irradiation + concurrent boost
Hypofractionated whole breast (H-WBI) irradiation with a concurrent boost
Intervention: Concurrent boost
Outcomes
Primary Outcomes
Percentage of Participants With In-breast Recurrence (Local Failure)
Time Frame: From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.
In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.
Secondary Outcomes
- Percentage of Participants Alive Without Disease(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Percentage of Participants With a Physician-reported Cosmetic Score of Excellent or Good at 3 Years(3 years)
- Translational Research of Single Nucleotide Polymorphisms (SNPs) in Transforming Growth Factor Beta 1 (TGFB1) and Ataxia-Telangiesctasia Mutated (ATM) Genes(From randomization to last follow-up.)
- Percentage of Participants Alive Without Distant Disease(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Correlation Between Dose-volume Data and Both Adverse Events and Efficacy(From randomization to end of follow-up.)
- Percentage of Participants Alive(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Number of Participants by Highest Grade Adverse Event Reported as Definitely, Probably, or Possibly Related to Protocol Treatment(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years.)
- Change in Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis Subscale Score From Baseline to 3 Years(Baseline and 3 years)
- Treatment Cost(From randomization to end of treatment.)