Single Fraction High-Gradient Partial Breast Irradiation in Treating Patients With Low-Risk Stage 0-I Breast Cancer

Evaluation of Single Fraction High-Gradient Partial Breast Irradiation as the Sole Method of Radiation Therapy for Low-Risk Stage 0 and I Breast Carcinoma

This phase I/II clinical trial studies the side effects of delivering radiation therapy in a single session instead of multiple treatments over several weeks and to see how well it works in treating patients with low-risk stage 0-I breast cancer. Partial-breast irradiation, a type of radiation therapy focused only to the part of the breast that has cancer in it, given at a lower dose than standard whole-breast radiation therapy. Single fraction high-gradient partial-breast irradiation may cause fewer side effects, help prevent breast cancer from coming back, and improve the appearance of the breast and quality of life of patients with breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Radiation: accelerated partial breast irradiation

Detailed Description

This is a phase I/II study which will evaluate the complication rates, local control, cosmetic results, and quality of life of single fraction high gradient partial breast irradiation (HG-PBI) when used as the sole method of radiation therapy for patients with pathologic stage 0 (=< 2 cm) or I carcinoma of the breast treated with partial mastectomy with histologically assessed negative surgical margins.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• AJCC 7th Edition stage 0 or I (TisN0 ≤ 2 cm or T1N0) histologically confirmed carcinoma of the breast, treated with partial mastectomy. Axillary sampling is required only for cases of invasive cancers. Tumor size is determined by the pathologist. Clinical size may be used if the pathologic size is indeterminate. Patients with invasive cancer must have no positive axillary lymph nodes with at least 6 axillary lymph nodes sampled or a negative sentinel node.
• Negative histologic margins of partial mastectomy or re-excision specimen. Margins generally are positive if there is invasive or noninvasive tumor at the inked resection margin, close but negative if the tumor is within 2 mm of the inked margin and negative if the tumor is at least 2 mm away from the inked edge.
• Invasive ductal, lobular, medullary, papillary, colloid (mucinous), tubular histologies, or mixed histologies (lesions ≤ 2 cm) that are estrogen or progesterone receptor positive and do not exhibit HER2/neu gene amplification OR ductal carcinoma in situ (lesions ≤ 2 cm).
• Systemic therapy, if planned, must be adjuvant in nature and not be scheduled to begin for at least 4 weeks after completion of HG-PBI.
• Good candidate for treatment per protocol in the judgment of the PI and/or treating physician following simulation.
• Postmenopausal status.
• Age ≥ 50 years at diagnosis.
• Able to understand and willing to sign IRB-approved written informed consent document.
• English speaker.

Exclusion Criteria:

• Presence of distant metastases.
• In situ lobular carcinoma or nonepithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (tumors in different quadrants of the breast, or tumors separated by at least 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy.
• Premenopausal status.
• Histologically confirmed positive axillary nodes in the ipsilateral axilla. Palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
• Prior non-hormonal therapy for the present breast cancer, including radiation therapy or chemotherapy.
• Diagnosis of systemic lupus erythematosis, scleroderma, or dermatomyositis.
• Diagnosis of a coexisting medical condition which limits life expectancy to < 2 years.
• Diagnosis of psychiatric or addictive disorders that would preclude obtaining informed consent.
• History of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Paget's disease of the nipple.
• Skin involvement, regardless of tumor size.
• Unsatisfactory breast for HG-PBI as determined by the treating physician. For example, if there is little breast tissue remaining between the skin and pectoralis muscle after surgery, treatment with HG-PBI is technically problematic.
• Partial mastectomy so extensive that the cosmetic result is fair or poor prior to HG-PBI as determined by the treating physician.
• Surgical margins which cannot be microscopically assessed or are positive at pathological evaluation.
• Time between final definitive breast procedure to HG-PBI simulation is greater than 8 weeks.

Inclusion of Women and Minorities

-Women and members of all races and ethnic groups are eligible for this trial. Because breast cancer occurs rarely in men, men will not be recruited for participation.

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
Experimental: Treatment (HG-PBI); Patients undergo single fraction high gradient-partial breast irradiation within 8 weeks after partial mastectomy.	Radiation: accelerated partial breast irradiation; Undergo HG-PBI; Other Names: APBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Are Free of Serious Treatment Related Toxicity	Quantified by estimating the rate of acute and late treatment-related grade 3 or higher toxicity (per CTCAE, v.4.0) or any other grade 4 or 5 toxicity attributed to the therapy. Toxicities of concern include breast pain, delayed wound healing, persistent seroma fluid accumulation, breast fibrosis and fat necrosis in the treated breast. Rare toxicities include radiation pneumonitis and pericarditis. Acute toxicities are defined as toxicities that occurred from start of treatment until day 90. Late toxicities are defined as toxicities that occurred from Day 91 until completion of 5 year follow-up.	Up to 5 years
Percentage of Patients Who Are Free of Breast Cancer in the Treated Breast	Percentage of patients without ipsilateral breast tumor recurrences (IBTR).	At 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Are Free of Breast Cancer in the Regional Lymph Nodes	Ipsilateral axilla, infraclavicular, supraclavicular, and internal mammary groups.	At 5 years
Percentage of Patients Who Are Free From Distant Metastases		At 5 years
Change in Quality of Life as Measured by the Mean Change From Baseline - EORTC QLC-C30	The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. For the global health and five functional scales (Cognitive Functioning, Emotional Functioning, Physical Functioning, Role Functioning, and Social Functioning) a high score correlates to a high level of functioning or a better outcome. For the three symptom scales and six single item scales (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite loss, Constipation, Diarrhea, Financial Difficulties) a high score correlates to high levels of symptoms or problems and a worse outcome.	2 weeks, 8 weeks, 6 months, 12 months, 18 months, 24 months, 36 months, year 4, and year 5
Change in Quality of Life as Measured by the Mean Change From Baseline - QLQ-BR23	The QLQ-BR23 incorporates five multi-item scales to assess body image, sexual functioning, systemic therapy side effects, breast symptoms, and arm symptoms. In addition, single items assess sexual enjoyment, future perspective and being upset by hair loss. All of the scales and single-item measures range in score from 0 to 100. For the four symptom scales (Systemic Therapy Side Effects, Upset by Hair Loss, Arm Symptoms, Breast Symptoms) a high score correlates to high levels of symptoms or problems and a worse outcome. For the four functional scales (Body Image, Future Perspective, Sexual Functioning, Sexual Enjoyment) a high score correlates to a high/healthy level of functioning or a better outcome	2 weeks, 8 weeks, 6 months, 12 months, 18 months, 24 months, 36 months, year 4, and year 5
Change in Quality of Life as Measured by the Mean Change From Baseline - Visual Analog Scale for Pain	The pain VAS is a unidimensional measure of pain intensity, used to record patients' pain progression, or compare pain severity between patients with similar conditions. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor (0) and "severe pain" at (10) with the patient's mark providing a range of scores from 0-100 millimeters. A higher score indicates greater pain intensity.	2 weeks, 8 weeks, 6 months, 12 months, 18 months, 24 months, 36 months, year 4, and year 5
Cosmesis as Measured by the Mean Change From Baseline - Breast Retraction Assessment (BRA)	This instrument includes a formula expressing the extent of displacement of the treated breast relative to the contralateral breast and other anatomical features.	8 weeks, 6 months, 12 months, 24 months, 36 months, year 4, and year 5
Cosmesis as Measured by the Mean Change From Baseline - Percentage Breast Retraction Assessment (pBRA)	This instrument includes a formula expressing the extent of displacement of the treated breast relative to the contralateral breast and other anatomical features. This is calculated from dividing the BRA score by the reference length from sternal notch to contralateral nipple and then multiplying that value by 100 to get a percentage.	8 weeks, 6 months, 12 months, 24 months, 36 months, year 4, and year 5
Cosmesis as Measured by the Mean Change From Baseline - Aronson Modified Harris Scale.	Using this scale, cosmesis is qualitatively evaluated by the treating radiation oncologist by comparing the treated breast with the contralateral breast using the Aronson Modified Scale. The global cosmetic result, appearance of the surgical scar, breast size, breast shape, skin color, location of the areola and nipple, and shape of the areola and nipple were scored on a 4-point scale. In this case 1 is 'excellent' with 4 being 'poor.'	8 weeks, 6 months, 12 months, 24 months, 36 months, year 4, and year 5
Number of Patients With Complications Using CTCAE v. 4.0	Acute complications are defined as complications that occurred from start of treatment until day 90. Late complications are defined as complications that occurred from Day 91 until completion of 5 year follow-up.	Up to 5 years
Number of Participants With Grade 3-4 Toxicities Using CTCAE v4.0	Acute toxicities are defined as toxicities that occurred from start of treatment until day 90. Late toxicities are defined as toxicities that occurred from Day 91 until completion of 5 year follow-up.	Up to 5 years
Percentage of Patients Undergoing Mastectomy on the Treated Side		At 5 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Imran Zoberi, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2014
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: February 27, 2014
• First Submitted That Met QC Criteria: February 28, 2014
• First Posted (Estimated): March 3, 2014

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 201401160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No