Radiation Therapy Boost Before Surgery for the Treatment of Non-metastatic Breast Cancer

Study Overview
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Brief Summary
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This phase II trial investigates the safety of delivering a part (boost) of radiation treatment before breast surgery in treating patients with breast cancer that has not spread to other places in the body (non-metastatic). Radiation therapy uses high energy photons/electrons to kill tumor cells and shrink tumors. Delivering a boost radiation treatment before surgery when doctors can still visualize the tumor on imaging may help to better target the tumor and decrease the volume of normal irradiated tissue. By so doing, doctors may achieve better cosmetic outcomes and possibly better tumor control.

Detailed Description
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PRIMARY OBJECTIVE: I. To demonstrate that the incidence of grade 3 or more wound complications in patients with non-metastatic node negative breast cancer who are eligible for breast conserving surgery (BCS) and treated with pre-operative radiation boost at 1 month after end of whole breast radiation is no worse than the rates in the current standard of care (6-20%). SECONDARY OBJECTIVE: I. To demonstrate that the physician reported cosmetic outcome at 1 and 3 years after the end of treatment is better than what has been reported for the current standard of practice for patients undergoing BCS and hypofractionated whole breast irradiation (WBI). TERTIARY/EXPLORATORY OBJECTIVES: I. To measure the acute and late radiation related toxicities such as radiation dermatitis, telangiectasia and fibrosis in this cohort of patients. II. To measure the pre-operative boost clinical target volume (CTV) and compare to the post-op CTV volume that would have been contoured as CTV if the boost was to be delivered post-operatively. III. To measure the incidence of fair/poor patient reported cosmetic outcome using the Breast Cancer Treatment Outcomes Scale (BCTOS) cosmetic scale. IV. To study the cancer biology before and after radiation treatment. OUTLINE: Prior to surgery, patients undergo radiation therapy boost over 4 fractions. Patients then undergo standard of care surgery 1-3 weeks from the last day of boost. 3 to 5 weeks after surgery, patients continue standard of care WBI in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1, 3, 6, 9, 12, 18, and 24 months

Official Title
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A Single Center Phase II Prospective Clinical Trial to Assess the Feasibility of Preoperative Radiation Boost in Breast Cancer Patients

Conditions
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Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Invasive Breast Carcinoma, Non-Metastatic Breast Carcinoma, Prognostic Stage 0 Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8

Intervention / Treatment
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* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Radiation: Radiation Boost
* Procedure: Therapeutic Surgical Procedure
* Radiation: Whole Breast Irradiation
* Other: Breast MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer patients with biopsy proven invasive cancer Clinically and radiographically node negative No indication of metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Synchronous bilateral invasive cancer allowed Negative serum pregnancy test within one month from the radiation therapy (RT) boost delivery Willingness to participate in the clinical trial and adhere to the study protocol Individuals of all races, genders and ethnic groups are eligible for this trial Exclusion Criteria: Need for neoadjuvant chemotherapy Inflammatory breast cancer (cT4) Multicentric tumor Prior ipsilateral breast or thoracic RT Contraindication for baseline magnetic resonance imaging (MRI) Contraindication for surgery Distant metastatic disease Other synchronous cancer (besides bilateral breast) Contraindication to radiation therapy (presence of scleroderma or other collagen vascular disease) Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (radiation therapy boost, WBI)<br>Prior to surgery, patients undergo radiation therapy boost over 4 fractions. Patients then undergo standard of care surgery 1-3 weeks from the last day of boost. 3 to 5 weeks after surgery, patients continue standard of care WBI in the absence of disease progression or unacceptable toxicity. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Radiation: Radiation Boost<br>* Undergo radiation therapy boost<br>* Other names: Radiotherapy Boost;Procedure: Therapeutic Surgical Procedure<br>* Undergo standard surgery<br>Radiation: Whole Breast Irradiation<br>* Undergo standard WBI<br>Other: Breast MRI<br>* A baseline breast MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in wound status from baseline every 3-6 months after WBI to access incidence of grade 3 or more wound complications after breast conserving surgery. | Wound complications will be assessed by the surgeon and radiation oncologist and graded using descriptions and grading scales found in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5 (CTCAE v 5.0). This will be calculated as a proportion based on the number of events in the study. Will report the proportion with a 95% confidence interval (CI) using the Clopper-Pearson method. | For at least 36 months after WBI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician reported cosmesis | Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor). | At 1 month after whole breast irradiation (WBI) | 
| Physician reported cosmesis | Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor). | At 12 months after WBI | 
| Physician reported cosmesis | Physician reported cosmesis will be assessed using the Harvard Cosmesis assessment Scale for Breast Cancer Patients which is a 4-point scale describing the breast cosmetic outcome (excellent, good, fair or poor). Will be reported as a proportion; CI will be calculated using the Clopper-Pearson model. | At 36 months after WBI |