Preoperative Single-Fraction Radiotherapy in Early Stage Breast Cancer

A Phase II Preoperative Single-Fraction Partial Breast Radiotherapy in Early Stage Breast Cancer: Analysis of Pathologic Response

This protocol seeks to build on the favorable results of the investigators' phase I trial (Pro00015617) by extending the findings to a larger cohort of subjects.In this study, the investigators hypothesize that 21Gy (Gray) as a single fraction can be delivered preoperatively to a larger group of subjects (n100).

The primary objective is to determine physician reported rates of good/excellent cosmesis at baseline and 6 months, 1, 2, and 3 years post-treatment as measured by the NRG cosmesis scale

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Stereotactic body radiotherapy ( SBRT)

Detailed Description

The study team hypothesizes that a single fraction of 21Gy can be delivered preoperatively to the intact breast tumor with acceptable cosmetic outcomes. Furthermore, the investigators anticipate that pre- and post-radiation breast tumor samples will provide an avenue for understanding breast cancer radiation response

Rationale for single-fraction preoperative technique

This trial is proposed to build on the favorable results of the investigators' phase I trial by extending the findings to a larger cohort of subjects. The preoperative approach has several advantages:

1. a small intact breast tumor results in significantly less uninvolved breast tissue receiving high radiation doses which likely decreases toxicity;
2. more accurate targeting of the high-risk areas of subclinical disease surrounding the tumor is possible,
3. smaller treatment volumes are amenable to dose escalation which can further accelerate treatment and improve accessibility for subjects,
4. this technical approach is widely utilized in other tumor sites and can be delivered at most radiation facilities
5. the pre-operative approach provides a novel opportunity to study breast cancer radiation response.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women with a biopsy proven diagnosis of ductal carcinoma in situ or invasive carcinoma of the breast

   a. Biopsy tissue (either slides or block) from outside institutions will be reviewed to confirm diagnosis.

2. Breast preservation candidates (no prior breast or nodal radiotherapy, no imaging evidence of multicentric or multifocal disease, no pregnant women, and no comorbid conditions precluding surgery)
3. Clinical T1N0M0 invasive carcinoma or Ductal carcinoma in situ (DCIS) < or equal to 2cm
4. 60 years of age or older or 50-59 with a low Oncotype score (0-17) Oncotype is not required for women diagnosed with DCIS.
5. Estrogen receptor positive (ER+), Human epidermal growth factor 2 negative (HER2-) HER-2 status is not required for women diagnosed with DCIS.
6. Women of child-bearing potential must consent to use adequate contraception during the course of the study. Female subjects must agree to use a medically acceptable contraceptives including: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use.
7. White blood cells (WBC) > 3000, Hemoglobin ( Hgb) > 9, platelets >100000 within 30 days of consent
8. Eligible for contrasted magnetic resonance imaging (MRI) on initial evaluation with glomerular filtration rate (GFR) ≥ 60 ml/min. A diagnostic MRI ordered within one month will be considered an acceptable alternative and will not be repeated.
9. Outside breast imaging will be reviewed at Duke to confirm findings are consistent with trial eligibility.

Exclusion Criteria:

1. Neoadjuvant chemotherapy
2. Breast implant in the breast to be treated with SBRT
3. Medical conditions that may increase risk for poor cosmetic outcome (i.e. Lupus, rheumatoid arthritis, scleroderma)
4. Subjects unable to receive study treatment planning secondary to body habitus or inability to lie flat on the stomach at length
5. HER2 positive
6. Positive serum pregnancy test
7. Insufficient breast imaging to judge clinical stage
8. Subjects without placement of a biopsy clip at the diagnostic procedure who are unwilling to undergo clip placement.
9. Subjects in whom treatment planning constraints cannot be met

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm 21Gy stereotactic radiotherapy; Subjects will receive a single fraction of 21Gy of stereotactic radiotherapy before proceeding to surgery.	Radiation: Stereotactic body radiotherapy ( SBRT); Single fraction of 21 Gy stereotactic radiotherapy (SBRT)delivered pre-operatively to subjects with early stage breast cancer; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis	Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	6 months
Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis	Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	1 year
Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis	Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	2 years
Number of Participants With Physician Reported Rates of Good/Excellent Cosmesis.	Physician will independently complete the physician NRG Oncology cosmesis scale at the designated time points. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis	Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	baseline
Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis	Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	6 months
Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis	Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	12 months
Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis	Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	2 year
Number of Participants With Patient Reported Rates of Good/Excellent Cosmesis	Patients will independently complete the patient NRG Oncology cosmesis scale at designated timepoints. The evaluation categories are Excellent; Good; Fair; Poor. The outcome measure is the rate of good or excellent cosmesis scores relative to all cosmesis evaluations. The higher the fraction is considered the better outcome.	3 year
Local Control in the Treated Breast Relative to Historic Controls	Local control consists of annual clinical examination combined with breast imaging	Through study completion estimated to be 10 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Gateway for Cancer Research
• Investigators: Principal Investigator: Rachel Blitzblau, MD PhD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2015
• Primary Completion (Actual): March 10, 2025
• Study Completion (Estimated): March 10, 2032

Study Registration Dates

• First Submitted: June 22, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimated): June 26, 2015

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: Pro00063848