Hypofractionated Radiation Therapy in Treating Participants With Breast Cancer Before Surgery

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well hypofractionated radiation therapy works in treating participants with breast cancer before 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
-----------------
PRIMARY OBJECTIVES: I. To determine the pathologic complete response (pCR) rate after hypofractionated radiotherapy to the whole breast alone, based on the postsurgical specimen. SECONDARY OBJECTIVES: I. To evaluate acute and late toxicity with preoperative radiation including grade >= 2 pneumonitis. II. To estimate the 5-year locoregional control, distant recurrence, invasive disease-free survival, cause-specific survival, and overall survival. CORRELATIVE AND EXPLORATORY OBJECTIVES: I. To evaluate patient-reported outcomes. II. To evaluate clinical features, treatment technique, dose-volume parameters, histologic and genetic variants associated with adverse events, and fair and poor cosmetic outcomes or unplanned surgical intervention. III. Evaluate tumor mutation signatures before and after radiation; correlate tumor mutation signatures before and after radiation with pathologic information at the time of surgery. IV. To describe the pathologic changes seen in breast cancer patients with preoperative radiation. OUTLINE: Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo standard of care surgery 4-16 weeks after radiation therapy. After completion of study treatment, participants are followed up at 12 weeks, 6, 12, 24, and 36 months, and 5 years after radiation therapy.

Official Title
-----------------
A Pilot/Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast Alone Before Breast Conserving Surgery

Conditions
-----------------
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8

Intervention / Treatment
-----------------
* Radiation: Hypofractionated Radiation Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histological confirmation of breast cancer Clinical stage T0-T2 N0 M0 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 120 days of last biopsy (breast) Able to complete all mandatory tests Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) Planned breast 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 Women of childbearing potential who are unwilling to employ adequate contraception Prior receipt of ipsilateral breast or chest wall radiation Recurrent breast cancer Indications for comprehensive regional nodal irradiation No neo-adjuvant therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (hypofractionated radiation therapy)<br>Participants undergo hypofractionated radiation therapy daily for 5 days, then undergo standard of care surgery 4-16 weeks after radiation therapy. | Radiation: Hypofractionated Radiation Therapy<br>* Undergo hypofractionated radiation therapy<br>* Other names: hypofractionation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response (pCR) Rate Defined as a Residual Tumor Burden of 0-1 in the Surgical Specimen | The proportion of successes (number of patients achieving pCR at time of definitive surgery) will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Adverse Events (AE) | The maximum grade for each type of acute AE will be recorded for each patient. Data will be summarized as frequencies and relative frequencies. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. | Up to 180 days post radiation therapy | 
| 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. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. | Up to 5 years post radiation therapy | 
| Locoregional Control | The cumulative incidence of locoregional recurrence will be estimated using a competing risks method (Gooley et al.). The competing risks will be distant breast cancer recurrence and death. | Up to 5 years | 
| Invasive Disease-free Survival | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals (CIs). | From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years | 
| Distant Recurrence |  | Up to 5 years | 
| Disease- Free Survival | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. | From registration until the time of disease recurrence or death due to any cause, assessed up to 5 years | 
| Cause-specific Survival | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. | From registration to death due to breast cancer assessed up to 5 years | 
| Overall Survival | Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% CIs. | From registration to death due to any cause assessed up to 5 years |