Hypofractionated Radiation Therapy or Standard Radiation Therapy in Treating Patients With Ductal Breast Carcinoma In Situ or Early Invasive Breast Cancer

Randomized Trial of Hypofractionated Whole Breast Irradiation Versus Conventionally Fractionated Whole Breast Irradiation for Ductal Carcinoma In Situ and Early Invasive Breast Cancer

This randomized phase II trial studies how well hypofractionated radiation therapy (RT) works compared to standard RT in treating patients with ductal breast carcinoma in situ (DCIS) or early invasive breast cancer. Radiation therapy (RT) uses high energy x-rays to kill tumor cells. Giving higher doses of RT over a shorter period of time may kill more tumor cells and have fewer side effects. It is not yet known if hypofractionated RT is more effective than standard RT in treating breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Invasive Breast Carcinoma; 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; Ductal Breast Carcinoma In Situ; Stage I Breast Cancer AJCC v6
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Other: Laboratory Biomarker Analysis; Radiation: External Beam Radiation Therapy; Radiation: External Beam Radiation Therapy; Radiation: Hypofractionated Radiation Therapy; Radiation: Whole Breast Irradiation; Radiation: Whole Breast Irradiation

Detailed Description

PRIMARY OBJECTIVES:

I. To compare patient-reported cosmetic outcome at 3 years using the Breast Cancer Treatment Outcomes Scale (BCTOS) for patients assigned to hypofractionated whole breast irradiation (HF-WBI) versus conventionally fractionated whole breast irradiation (CF-WBI).

SECONDARY OBJECTIVES:

I. To determine patient-reported cosmetic outcome using the BCTOS at 6 months, 1, 2, 4, and 5 years.

II. To determine physician-rated cosmetic outcome at 6 months, 1, 2, 3, 4, and 5 years using the Radiation Therapy and Oncology Group (RTOG) scale for physician assessment.

III. To determine the level of agreement between patient-rated cosmetic outcome and physician-rated cosmetic outcome at the various time points assessed.

IV. To determine the 5-year and risk of pathologically-confirmed invasive and/or in situ ipsilateral breast tumor recurrence (IBTR) for patients with ductal carcinoma in situ (DCIS) and early invasive breast cancer.

V. To determine patient-reported functional status and breast pain using the BCTOS at 6 months, 1, 2, 3, 4, and 5 years after treatment.

VI. To determine maximal acute (within 6 weeks of treatment) and late (more than 6 weeks after treatment) skin and soft tissue toxicities using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 scale.

VII. To determine the relationship between the volume of breast tissue receiving excessive dose (defined as greater than 105% of the prescription dose) and the risk of adverse cosmesis.

VIII. To determine the relationship between bra cup size and the risk of adverse cosmesis.

IX. To determine whether there is a statistical interaction between breast volume and volume of tissue receiving greater than 105% of the prescription dose in predicting adverse cosmesis.

X. To determine in an exploratory analysis whether any other demographic, clinical, and pathologic factors correlate with risk of adverse cosmesis, quality of life, body image, image investment, and risk of IBTR.

XI. To determine if the C-509T variant allele of transforming growth factor-beta (TGF-beta) is associated with an increased risk of grade 2 or higher fibrosis (as determined by the Subjective, Objective, Medical Management, Analytic [SOMA] scale) three years after completion of radiation.

XII. To compare the cost of radiation for patients treated on the two treatment arms.

XIII. To compare patient quality of life, body image, and appearance investment for the two treatment arms using the Functional Assessment of Cancer Therapy-Breast (FACT-B), Appearance Schemas Inventory-Revised (ASI-R), and Body Image Scale, respectively.

XIV. To contribute additional blood samples to protocol LAB02-086 which is a case-control study investigating deoxyribonucleic acid (DNA) repair phenotypes and genotypes in breast cancer.

XV. To assess the psychometric profile of the Functional Assessment of Cancer Therapy-Breast (FACT-B) version 4 in collaboration with investigators from the Department of Medical Social Science, Northwestern University Feinberg School of Medicine.

XVI. To determine the influence of oncoplastic lumpectomy on the following outcomes: physician- and patient-reported cosmetic outcomes, other patient-reported health-related quality of life outcomes, and photographic measurements of breast cosmetic outcome.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.

ARM II: Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.

After completion of study treatment, patients are followed up at 6 months and then annually for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Texas
    • Conroe, Texas, United States, 77384
      • MD Anderson in The Woodlands
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77079
      • MD Anderson West Houston
    • League City, Texas, United States, 77573
      • MD Anderson League City
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically confirmed ductal carcinoma in situ of the breast or early invasive breast cancer defined as pathologic stage Tis, T1, or T2, N0, N1mic, or N1a (pathologic staging of the axilla is required for all patients with invasive disease but is not required for patients with ductal carcinoma in situ [DCIS] only); (upfront pathologic stage cannot be assigned to patients treated with neoadjuvant chemotherapy; for such patients, the criteria for pathologic stage shall be applied to the initial clinical stage)
• Treatment with breast conserving surgery
• Final surgical margins must be negative, defined as no evidence for ductal carcinoma in situ or invasive breast cancer touching the inked surgical margin; if the invasive or in situ breast cancer approaches within less than 1 mm of the final surgical margin, then a re-excision is strongly encouraged; lobular carcinoma in situ at the final surgical margin will be disregarded
• Age 40 years or older. This age cutoff is justified because breast cancers in women under the age of 40 are known to have a significantly higher risk of IBTR presumably due to underlying biologic differences.
• Female sex.
• Attending radiation oncologist declares intention to treat the whole breast only and that a third radiation field to treat regional lymph nodes is not planned (radiation of the undissected level I/II axilla with high tangents is allowed)
• If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer
• Patients must be enrolled on the trial within 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of concurrent cytotoxic chemotherapy

Exclusion Criteria:

• Pathologic or clinical evidence for a stage T3 or T4 breast cancer
• Pathologic evidence for involvement of 4 or more axillary lymph nodes, or imaging evidence of involvement of infraclavicular, supraclavicular, or internal mammary lymph nodes
• Clinical or pathologic evidence for distant metastases
• Any prior diagnosis of invasive or ductal carcinoma in situ breast cancer in either breast
• Current diagnosis of bilateral breast cancer
• History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast
• Patients not fluent in English or Spanish (The BCTOS will be available in these two languages)
• Patient is pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (HF-WBI); Patients undergo HF-WBI comprising external beam RT 5 days a week for approximately 3 weeks.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Laboratory Biomarker Analysis; Optional correlative studies; Radiation: External Beam Radiation Therapy; Undergo HF-WBI; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Radiation: External Beam Radiation Therapy; Undergo CF-WBI; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Radiation: Hypofractionated Radiation Therapy; Undergo HF-WBI; Other Names: Hypofractionated Radiotherapy; hypofractionation; Radiation: Whole Breast Irradiation; Undergo HF-WBI; Radiation: Whole Breast Irradiation; Undergo CF-WBI
Active Comparator: Arm II (CF-WBI); Patients undergo CF-WBI comprising external beam RT 5 days a week for approximately 5 weeks.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Other: Laboratory Biomarker Analysis; Optional correlative studies; Radiation: External Beam Radiation Therapy; Undergo HF-WBI; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Radiation: External Beam Radiation Therapy; Undergo CF-WBI; Other Names: EBRT; Definitive Radiation Therapy; External Beam Radiation; External Beam Radiotherapy; External Beam RT; external radiation; External Radiation Therapy; external-beam radiation; Radiation, External Beam; Radiation: Whole Breast Irradiation; Undergo HF-WBI; Radiation: Whole Breast Irradiation; Undergo CF-WBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Scores of Either <2.5 or >=2.5 on the Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis	BCTOS cosmesis score range from 1 to 4, and scores of 2.5 or more indicate adverse cosmetic outcomes.	3 years after completing radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Panel Physicians Rated Cosmesis	A group of three attending physicians blinded to the treatment scored the photographs using the Radiation Therapy and Oncology Group (RTOG) criteria. RTOG scale range from 1 (excellent), 2 (good), 3 (fair), and 4 (poor).	3 years after completing radiation therapy.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Benjamin D Smith, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Weng JK, Lei X, Schlembach P, Bloom ES, Shaitelman SF, Arzu IY, Chronowski G, Dvorak T, Grade E, Hoffman K, Perkins G, Reed VK, Shah SJ, Stauder MC, Strom EA, Tereffe W, Woodward WA, Hortobagyi GN, Hunt KK, Buchholz TA, Smith BD. Five-Year Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation. Int J Radiat Oncol Biol Phys. 2021 Oct 1;111(2):360-370. doi: 10.1016/j.ijrobp.2021.05.004. Epub 2021 May 13.
• Grossberg AJ, Lei X, Xu T, Shaitelman SF, Hoffman KE, Bloom ES, Stauder MC, Tereffe W, Schlembach PJ, Woodward WA, Buchholz TA, Smith BD. Association of Transforming Growth Factor beta Polymorphism C-509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1751-1757. doi: 10.1001/jamaoncol.2018.2583.
• Shaitelman SF, Schlembach PJ, Arzu I, Ballo M, Bloom ES, Buchholz D, Chronowski GM, Dvorak T, Grade E, Hoffman KE, Kelly P, Ludwig M, Perkins GH, Reed V, Shah S, Stauder MC, Strom EA, Tereffe W, Woodward WA, Ensor J, Baumann D, Thompson AM, Amaya D, Davis T, Guerra W, Hamblin L, Hortobagyi G, Hunt KK, Buchholz TA, Smith BD. Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial. JAMA Oncol. 2015 Oct;1(7):931-41. doi: 10.1001/jamaoncol.2015.2666.

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2011
• Primary Completion (Actual): November 30, 2020
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: December 20, 2010
• First Submitted That Met QC Criteria: December 23, 2010
• First Posted (Estimated): December 24, 2010

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Ductal, Breast
• Other Study ID Numbers: 2010-0559 (Other Identifier: M D Anderson Cancer Center); NCI-2011-00253 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No