Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

Study Overview
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Brief Summary
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This randomized phase II trial studies how well hypofractionated radiation therapy works in preventing the return of tumor cells in breast cancer patients following surgery. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the 24-month complication rate of 5 fraction whole radiotherapy +/- concurrent boost as compared to 15 fraction radiotherapy +/- sequential boost. SECONDARY OBJECTIVES: I. To evaluate acute and late toxicity. II. To estimate the 5-year locoregional control, invasive disease-free survival and overall survival. TERTIARY OBJECTIVES: I. To evaluate fatigue, and other patient-reported outcomes. II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with fair and poor cosmetic outcomes or unplanned surgical intervention. III. To evaluate the costs and comparative effectiveness of treatment. IV. Compare the use of photon therapy with spot scanning proton therapy in two different hypo-fractionated whole breast schemas. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo radiation therapy in 15 daily fractions for 10 days. ARM II: Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days. After completion of study treatment, patients are followed up to 5 years.

Official Title
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A Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast Alone After Breast Conserving Surgery

Conditions
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Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage IIA Breast Cancer AJCC v6 and v7, Stage IIB Breast Cancer AJCC v6 and v7, Stage IIIA Breast Cancer AJCC v7

Intervention / Treatment
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* Radiation: Hypofractionated Radiation Therapy
* Other: Quality-of-Life Assessment
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation of breast cancer Pathologic stage T0-T3N0-N1M0 Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2 Able to and provides Institutional Review Board (IRB) approved study specific written informed consent Study entry must be within 12 weeks of last surgery (breast or axilla) or last chemotherapy (if applicable) Able to complete all mandatory tests Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) Fair, good or excellent cosmesis, as determined by trained nurse assessment using the Harvard Cosmetic Scale Radiotherapy must begin within 12 weeks of the last breast cancer surgery or the last dose of adjuvant chemotherapy Breast conserving surgery and indications for whole breast radiotherapy Exclusion Criteria: Medical contraindication to receipt of radiotherapy Severe active co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or providing informed consent Active systemic lupus or scleroderma Pregnancy Prior receipt of ipsilateral breast or chest wall radiation Positive margins on ink after definitive surgery either for ductal carcinoma in situ (DCIS) or invasive cancer History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior study entry Recurrent breast cancer Indications for comprehensive regional nodal irradiation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 2 (hypofractionated radiation therapy, 5 fractions)<br>Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo hypofractionated radiation therapy in 5 daily fractions for 5 days. | Radiation: Hypofractionated Radiation Therapy<br>* Undergo hypofractionated radiation therapy<br>* Other names: hypofractionation;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Experimental: Arm I (radiation therapy, 15 fractions)<br>Within 12 weeks of breast cancer surgery or adjuvant chemotherapy, patients undergo standard radiation therapy in 15 daily fractions for 10 days. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Radiation: Radiation Therapy<br>* hypofractionated radiation therapy<br>* Other names: Therapy, Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complication Rate, Defined as the Percentage of Women Who Develop Grade 3 or Higher Late Adverse Event and/or Deterioration of Cosmesis From Excellent/Good to Fair/Poor or From Fair to Poor | The complication rate will be reported by arm. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cause-specific Survival | Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% CIs. Comparison between arms will employ a log-rank test. | From registration to death due to breast cancer, assessed up to 5 years | 
| Disease- Free Survival | Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% CIs. Comparison between arms will employ a log-rank test. | From study registration until the time of disease recurrence or death due to any cause, assessed up to 5 years | 
| Distant Recurrence Defined as Metastatic Cancer That Has Either Been Biopsy Confirmed or Clinically Diagnosed as Recurrent Invasive Breast Cancer |  | Up to 5 years | 
| Incidence of Acute Adverse Events (AEs) | The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. The relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests. | Up to 180 days post-radiation therapy (RT) | 
| Incidence of Late Adverse Events | The maximum grade for each type of late AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. The relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests. | Up to 5 years post-RT | 
| Invasive Disease-free | Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% confidence intervals (CIs). Comparison between arms will employ a log-rank test. | From study registration until the time of invasive disease recurrence (not including ductal carcinoma in situ [DCIS]) or death due to any cause, assessed up to 5 years | 
| Locoregional Control | The cumulative incidence of locoregional recurrence will be estimated using a competing risks method by treatment arm. The competing risks will be distant breast cancer recurrence and death. Comparison between arms will employ Fine-Gray regression. | Up to 5 years | 
| Overall Survival | Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% CIs. Comparison between arms will employ a log-rank test. | From registration to death due to any cause, assessed up to 5 years |