Higher Per Daily Treatment-Dose Radiation Therapy or Standard Per Daily Treatment Radiation Therapy in Treating Patients With Early-Stage Breast Cancer That Was Removed by Surgery

A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer

RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as effective as standard per daily radiation therapy in treating breast cancer.

PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per daily radiation therapy with concomitant boost works compared to standard per daily radiation therapy with a sequential boost in treating patients with early-stage breast cancer that was removed by surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Standard fractionation whole breast irradiation; Radiation: Sequential boost; Radiation: Hypofractionated whole breast irradiation; Radiation: Concurrent boost

Detailed Description

OBJECTIVES:

Primary

• To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.

Secondary

• To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost.
• To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and normal tissue complication probability (NTCP) calculations.
• To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity.
• To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost.
• To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI.
• If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
• To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 vs. ≥ 50 years), prior chemotherapy (yes vs. no), estrogen-receptor status (+ vs. -), and histology grade (1-2 vs. 3). Patients are randomized to 1 of 2 treatment arms. Treatment begins within 9 weeks of last surgery or chemotherapy delivery.

After completion of study therapy, patients are followed at 1 month, at 6 months, and then yearly.

• Study Type: Interventional
• Enrollment (Actual): 2354
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation-Saint John Regional Hospital
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre at Grand River Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Stronach Regional Health Centre at Southlake
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital-Civic Campus
    • Ottawa, Ontario, Canada, K2H 8P4
      • Irving Greenberg Family Cancer Centre
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Hôpital de la Cité-de-la-Santé
    • Montreal, Quebec, Canada, H3H 2R9
      • The Research Institute of the McGill University Health Centre (MUHC)
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM - Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSSEMTL-Hopital Maisonneuve-Rosemont
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• Hong Kong
  • Chai Wan, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
• Japan
  • Suntou
    • Shizuoka City, Suntou, Japan, 411-8777
      • Shizuoka Cancer Center
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System-Severance Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center-Korea
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
  • Singapore, Singapore, 119074
    • National University Hospital Singapore
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Birmingham, Alabama, United States, 35243
      • The Kirklin Clinic at Acton Road
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
    • Scottsdale, Arizona, United States, 85251
      • 21st Century Oncology-Scottsdale
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates-West Orange Grove
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Chico, California, United States, 95926
      • Enloe Medical Center
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Dublin, California, United States, 94568
      • Epic Care-Dublin
    • El Segundo, California, United States, 90245
      • 21st Century Oncology - El Segundo
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • San Jose, California, United States, 95128
      • Santa Clara Valley Medical Center
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Edwards, Colorado, United States, 81632
      • Shaw Cancer Center
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • John Fitzgerald Kennedy Medical Center
    • Daytona Beach, Florida, United States, 32117
      • Florida Hospital Memorial Medical Center
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Fort Walton Beach, Florida, United States, 32547
      • 21st Century Oncology - Fort Walton Beach
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center - Jacksonville
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network-Southside Cancer Center
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network-Florida Cancer Center Beaches
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital-Holtz Children's Hospital
    • Orange Park, Florida, United States, 32073
      • 21st Century Oncology-Orange Park
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
    • Palatka, Florida, United States, 32177
      • Cancer Center of Putnam
    • Saint Augustine, Florida, United States, 32086
      • Integrated Community Oncology Network-Flager Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • The Villages, Florida, United States, 32159
      • The Villages Regional Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Cumming, Georgia, United States, 30041
      • Northside Hospital-Forsyth
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60657
      • Advocate Illinois Masonic Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Freeport, Illinois, United States, 61032
      • Freeport Memorial Hospital/Leonard C Ferguson Cancer Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • Normal, Illinois, United States, 61761
      • Carle Cancer Institute Normal
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Rockford, Illinois, United States, 61104
      • Swedish American Hospital
    • Springfield, Illinois, United States, 62702
      • Saint John's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Avon, Indiana, United States, 46123
      • IU Health West Hospital
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East
    • Indianapolis, Indiana, United States, 46256
      • Community Cancer Center North
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Muncie, Indiana, United States, 47303
      • IU Health Ball Memorial Hospital
  • Iowa
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Dubuque, Iowa, United States, 52001
      • Finley Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Prairie Village, Kansas, United States, 66208
      • Kansas City NCI Community Oncology Research Program
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Owensboro, Kentucky, United States, 42303
      • Owensboro Health Mitchell Memorial Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21229
      • Saint Agnes Hospital
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology in Howard County
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
    • Salisbury, Maryland, United States, 21801
      • TidalHealth Peninsula Regional
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Danvers, Massachusetts, United States, 01923
      • Mass General/North Shore Cancer Center
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Clarkston, Michigan, United States, 48346
      • GenesisCare USA - Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Farmington Hills, Michigan, United States, 48336
      • Beaumont Hospital - Farmington Hills
    • Farmington Hills, Michigan, United States, 48334
      • GenesisCare USA - Farmington Hills
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Monroe, Michigan, United States, 48162
      • KCC Radiation Oncology at Monroe Cancer Center
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Southfield, Michigan, United States, 48075
      • Ascension Providence Hospitals - Southfield
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital - Troy
    • Troy, Michigan, United States, 48098
      • GenesisCare USA - Troy
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Mayo Clinic Health System in Albert Lea
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Mankato, Minnesota, United States, 56001
      • Mayo Clinic Health Systems-Mankato
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Chesterfield, Missouri, United States, 63017
      • Saint Luke's Hospital
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Kansas City, Missouri, United States, 64154
      • University of Kansas Cancer Center - North
    • Kansas City, Missouri, United States, 64131
      • The University of Kansas Cancer Center-South
    • Lee's Summit, Missouri, United States, 64064
      • University of Kansas Cancer Center - Lee's Summit
    • Liberty, Missouri, United States, 64068
      • Liberty Radiation Oncology Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Brick, New Jersey, United States, 08724
      • Ocean Medical Center
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore Medical Center
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • Pennington, New Jersey, United States, 08534
      • Capital Health Medical Center-Hopewell
    • Red Bank, New Jersey, United States, 07701
      • Riverview Medical Center/Booker Cancer Center
    • Sparta, New Jersey, United States, 07871
      • Sparta Cancer Treatment Center
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Las Cruces, New Mexico, United States, 88011
      • Memorial Medical Center - Las Cruces
  • New York
    • Albany, New York, United States, 12208
      • Saint Peter's Health Partners
    • Albany, New York, United States, 12206
      • New York Oncology Hematology PC - Albany
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Canandaigua, New York, United States, 14424
      • Sands Cancer Center
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Cooperstown, New York, United States, 13326
      • Mary Imogene Bassett Hospital
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Ithaca, New York, United States, 14850
      • Cayuga Medical Center
    • Lake Success, New York, United States, 11042
      • Northwell Health NCORP
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Oncology Associates
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Rochester, New York, United States, 14606
      • Wilmot Cancer Institute Radiation Oncology at Greece
    • Sleepy Hollow, New York, United States, 10591
      • Memorial Sloan Kettering Sleepy Hollow
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau
    • White Plains, New York, United States, 10601
      • Dickstein Cancer Treatment Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Morehead City, North Carolina, United States, 28557
      • The Coleman Radiation Center-Carteret General Hospital
    • New Bern, North Carolina, United States, 28561
      • CarolinaEast Medical Center
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Supply, North Carolina, United States, 28462
      • NHRMC Radiation Oncology - Supply
    • Wilmington, North Carolina, United States, 28401
      • New Hanover Regional Medical Center/Zimmer Cancer Center
    • Wilmington, North Carolina, United States, 28401
      • NHRMC Radiation Oncology - 16th Street
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Barberton, Ohio, United States, 44203
      • Summa Health System - Barberton Campus
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Medina, Ohio, United States, 44256
      • Summa Health Medina Medical Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Ravenna, Ohio, United States, 44266
      • University Hospitals Portage Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Center
    • Grants Pass, Oregon, United States, 97527
      • Three Rivers Community Hospital
    • Medford, Oregon, United States, 97504
      • Providence Medford Medical Center
    • Medford, Oregon, United States, 97504
      • Rogue Valley Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Beaver, Pennsylvania, United States, 15009
      • UPMC-Heritage Valley Health System Beaver
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Furlong, Pennsylvania, United States, 18925
      • Fox Chase Cancer Center Buckingham
    • Gettysburg, Pennsylvania, United States, 17325
      • Adams Cancer Center
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Hanover, Pennsylvania, United States, 17331
      • Cherry Tree Cancer Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC-Johnstown/John P. Murtha Regional Cancer Center
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Meadowbrook, Pennsylvania, United States, 19046
      • Holy Redeemer Hospital and Medical Center
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital
    • Monroeville, Pennsylvania, United States, 15146
      • Intercommunity Cancer Center
    • Moon, Pennsylvania, United States, 15108
      • UPMC-Coraopolis/Heritage Valley Radiation Oncology
    • Natrona Heights, Pennsylvania, United States, 15065
      • Allegheny Valley Hospital
    • New Castle, Pennsylvania, United States, 16105
      • UPMC Jameson
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC-Saint Margaret
    • Pittsburgh, Pennsylvania, United States, 15236
      • UPMC Jefferson Regional Radiation Oncology
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC-Saint Clair Hospital Cancer Center
    • Reading, Pennsylvania, United States, 19605
      • Penn State Health Saint Joseph Medical Center
    • Sellersville, Pennsylvania, United States, 18960
      • Grand View Hospital
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • Upland, Pennsylvania, United States, 19013
      • Crozer-Chester Medical Center
    • Washington, Pennsylvania, United States, 15301
      • UPMC Washington Hospital Radiation Oncology
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • York, Pennsylvania, United States, 17403
      • WellSpan Health-York Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29601
      • Greenville Health System Cancer Institute-Andrews
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Hilton Head Island, South Carolina, United States, 29926
      • The Radiation Oncology Center-Hilton Head/Bluffton
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • West Columbia, South Carolina, United States, 29169
      • Lexington Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Texas
    • Arlington, Texas, United States, 76014
      • Texas Oncology-Arlington South
    • Austin, Texas, United States, 78705
      • Texas Oncology-Austin Midtown
    • Austin, Texas, United States, 78745
      • Texas Oncology - South Austin Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology Bedford
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Denison, Texas, United States, 75020
      • Texas Oncology - Denison Cancer Center
    • Denton, Texas, United States, 76201
      • Texas Oncology-Denton South
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology - Fort Worth Cancer Center
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
    • Irving, Texas, United States, 75061
      • Baylor Medical Center at Irving
    • Lewisville, Texas, United States, 75067
      • Texas Oncology - Lewisville
    • Odessa, Texas, United States, 79761
      • West Texas Cancer Center
    • Plano, Texas, United States, 75093
      • Texas Oncology-Plano West
    • Round Rock, Texas, United States, 78665
      • Texas Oncology-Seton Williamson
    • Round Rock, Texas, United States, 78681
      • Texas Oncology - Round Rock Cancer Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas- Northeast
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology Cancer Center Sugar Land
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology-Wichita Falls Texoma Cancer Center
  • Utah
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Inova Alexandria Hospital
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Fishersville, Virginia, United States, 22939
      • Augusta Health Center for Cancer and Blood Disorders
    • Hampton, Virginia, United States, 23666
      • Sentara Cancer Institute at Sentara CarePlex Hospital
    • Harrisonburg, Virginia, United States, 22801
      • Sentara Rockingham Memorial Hospital Hahn Cancer Center
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center - Portsmouth
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
    • Virginia Beach, Virginia, United States, 23454
      • Sentara Virginia Beach General Hospital
  • Washington
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Kennewick, Washington, United States, 99336
      • Tri-Cities Cancer Center
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Sequim, Washington, United States, 98384
      • Olympic Medical Cancer Care Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Cancer Care Northwest-North Spokane
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare Regional Medical Center - Appleton
    • Beloit, Wisconsin, United States, 53511
      • Beloit Memorial Hospital
    • Eau Claire, Wisconsin, United States, 54703
      • Mayo Clinic Health System Eau Claire Hospital-Luther Campus
    • Fond Du Lac, Wisconsin, United States, 54935
      • Saint Agnes Hospital/Agnesian Cancer Center
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Green Bay, Wisconsin, United States, 54301
      • Bellin Memorial Hospital
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Froedtert Menomonee Falls Hospital
    • Mequon, Wisconsin, United States, 53097
      • Ascension Columbia Saint Mary's Hospital Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Hospital - Milwaukee
    • Racine, Wisconsin, United States, 53405
      • Ascension All Saints Hospital
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Saint Vincent Hospital Cancer Center at Sturgeon Bay
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

1. Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole breast irradiation with boost without regional nodal irradiation planned
2. The patient must be female

3. The patient must meet at least one of the three following criteria:

   • A. Pathological stage I, II Breast Cancer AND at least one of the following:

     • Age < 50 years or
     • Positive axillary nodes or
     • Lymphovascular space invasion or
     • 2 or more close resection margins (> 0 mm to ≤ 2 mm) or
     • 1 close resection margin and extensive intraductal component (EIC) [Per College of American Pathologist (CAP) Recommendation] or
     • Focally positive resection margins or
     • Non-hormone sensitive breast cancer (estrogen receptor (ER)- and progesterone receptor(PR)-negative) or
     • Grade III histology or
     • Oncotype recurrence score > 25 or
   • B. Pathological stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age <50 years or
   • C. Post-neoadjuvant pathological 0, I, II breast cancer resected by lumpectomy after neoadjuvant systemic therapy
4. Study entry must be within 50 days from whichever comes later: last surgery (breast or axilla) or last chemotherapy. The day of surgery is Day "0".
5. If multifocal breast cancer, then it must have been resected through a single lumpectomy incision with negative margins

6. Breast-conserving surgery with margins defined as follows: (also see 3.1.3 for eligibility)

   • Negative margins defined as no tumor at the resected specimen edge.

   • Close resection margins > 0 mm to ≤ 2 mm. as follows:

     • One close resection margin and EIC (per College of American Pathologist (CAP) Recommendation)
     • 2 or more close resection margins.
   • A focally positive resection margin

7. For invasive breast cancer the axilla must be staged by one of the following:

   • Sentinel node biopsy alone, if sentinel node is negative, i.e. any of the following:

     • pN0: no regional lymph node metastasis identified histologically,
     • pN0(i-): pN0 and immunohistochemical (IHC) negative, or
     • pN0(i+): pN0 and IHc positive;

   • Sentinel node biopsy alone, OR followed by axillary node dissection per investigator discretion, for clinically node negative patients as described below:

     • microscopic sentinel node positive (pN1mic)
     • one or two sentinel nodes positive (pN1) without extracapsular extension
     • negative sentinel node biopsy after neoadjuvant chemotherapy

   • Axillary node dissection is required following sentinel node (SN) biopsy with a minimum total of 6 axillary nodes if any of the following exist:

     • for > 2 positive SN
     • any positive SN biopsy after neoadjuvant chemotherapy
     • for clinically (by either imaging or examination) T3 disease
     • for extracapsular extension
   • Axillary dissection alone (with a minimum of 6 axillary nodes)
8. Age ≥ 18
9. CT-imaging of the ipsilateral breast within 28 days prior to study entry for the radiation treatment planning. Must be able to delineate on CT scan the extent of the target lumpectomy cavity for boost

10. Appropriate stage for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup:

    • History/physical examination, including breast exam (inspection and palpation of the breasts) and documentation of weight and Zubrod Performance Status of 0-2 within 28 days prior to study entry;
    • Right and left mammography within 90 days of diagnostic biopsy establishing diagnosis
11. Patients must have had ER analysis performed on the primary breast tumor prior to study entry according to current American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) Guideline Recommendations for hormone receptor testing. If negative for ER, assessment of PR must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing (http://www.asco.org)

12. Complete blood count (CBC)/differential obtained within 14 days prior to study entry, with adequate bone marrow function defined as follows:

    • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3
    • Platelets ≥ 75,000 cells/mm3
    • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
13. Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry
14. Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy
15. Patient must provide study specific informed consent prior to study entry
16. Breast implants allowed

Exclusion criteria:

1. American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, M1 pathologic stages III or IV breast cancer
2. Treatment plan that includes regional node irradiation
3. Prior invasive non-breast malignancy (except non-melanomatous skin cancer, carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
4. Prior invasive or in-situ carcinoma of the breast [-prior lobular carcinoma in situ (LCIS) is eligible]
5. Two or more breast cancers not resectable through a single lumpectomy incision
6. Bilateral breast cancer
7. DCIS only (without an invasive component) and age ≥ 50 years
8. DCIS nuclear grade 1 or 2 only (without an invasive component) and age < 50 years
9. Invasive breast cancer and low risk for 5-year in breast recurrence after lumpectomy with negative margins that does not meet one of the eligibility factors in 3.1.3.
10. Unable to delineate on CT scan the extent of the target lumpectomy cavity for boost (Placement of surgical clips to assist in treatment planning of the boost is strongly recommended, see Section 6.4.2 for details)
11. Suspicious unresected microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
12. Non-epithelial breast malignancies such as sarcoma or lymphoma
13. Paget's disease of the nipple
14. Male breast cancer
15. Prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation therapy fields
16. Intention to administer concurrent chemotherapy for current breast cancer.

17. Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
    • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
    • Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
18. Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception
19. Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash
20. Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent

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
Active Comparator: Whole breast irradiation + sequential boost; Standard fractionation whole breast irradiation (WBI) with sequential boost.	Radiation: Standard fractionation whole breast irradiation; Target-based radiation using three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) to deliver 25 fractions of 2.0 Gy for a total dose of 50.0 Gy or 16 fractions of 2.67 Gy for a total dose of 42.7 Gy. Must begin within 9 weeks of last surgery or chemotherapy delivery.; Other Names: three-dimensional conformal radiation therapy (3D-CRT); intensity-modulated radiation therapy (IMRT); Radiation: Sequential boost; 6 fractions of 2.0 Gy per fraction for a total dose of 12 Gy or 7 fractions of 2.0 Gy for a total dose of 14 Gy to the lumpectomy cavity. May be given by either electron beam or photon beams using either 3D-CRT or IMRT. Begins without a treatment break after completion of the treatment to the entire breast.
Experimental: Hypofractionated whole breast irradiation + concurrent boost; Hypofractionated whole breast (H-WBI) irradiation with a concurrent boost	Radiation: Hypofractionated whole breast irradiation; Target-based radiation using three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) to deliver 15 fractions of 2.67 Gy for a total dose of 40.0 Gy. Must begin within 9 weeks of last surgery or chemotherapy delivery.; Other Names: three-dimensional conformal radiation therapy (3D-CRT); intensity-modulated radiation therapy (IMRT); Radiation: Concurrent boost; 15 fractions of 3.2 Gy for a total dose of 48 Gy to the lumpectomy cavity. Given concurrently with treatment to the entire breast. May be given by either electron beam or photon beams using either 3D-CRT or IMRT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With In-breast Recurrence (Local Failure)	In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.	From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive	Failure is defined as death due to any cause. Failure time (overall survival time) is defined as the time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.	From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.
Percentage of Participants Alive Without Disease	Disease-free survival (DFS) time is defined as time from randomization to local-regional disease recurrence, distant metastases, second/new primary, death due to any cause or last known follow-up (censored). DFS rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.	From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.
Percentage of Participants Alive Without Distant Disease	Distant disease-free survival (DDFS) time is defined as time from randomization to distant metastases, second/new primary, death due to any cause or last known follow-up (censored). DDFS rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.	From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.
Number of Participants by Highest Grade Adverse Event Reported as Definitely, Probably, or Possibly Related to Protocol Treatment	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data	From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years.
Change in Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis Subscale Score From Baseline to 3 Years	The BCTOS cosmesis subscale score measures perceived aesthetic (e.g., breast shape) status . Patients rated each item using a four-point scale evaluating the differences between the treated and the untreated breast (1=no difference, 2=slight difference, 3=moderate difference, 4=large difference) with higher scores indicating a worse outcome. The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 3 years minus the value at baseline. A positive change reflects a decline at 3 years and a negative change reflects an improvement at 3 years.	Baseline and 3 years
Percentage of Participants With a Physician-reported Cosmetic Score of Excellent or Good at 3 Years	Physicians rated cosmesis using a four point scale: Excellent: When compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast.; Good: There is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast.; Fair: Obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast.; Poor: Marked change in the appearance of the treated breast involving more than a quarter of the breast tissue.	3 years
Correlation Between Dose-volume Data and Both Adverse Events and Efficacy		From randomization to end of follow-up.
Translational Research of Single Nucleotide Polymorphisms (SNPs) in Transforming Growth Factor Beta 1 (TGFB1) and Ataxia-Telangiesctasia Mutated (ATM) Genes		From randomization to last follow-up.
Treatment Cost		From randomization to end of treatment.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): January 25, 2022

Study Registration Dates

• First Submitted: May 5, 2011
• First Submitted That Met QC Criteria: May 5, 2011
• First Posted (Estimate): May 6, 2011

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage IA breast cancer; stage IB breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-negative breast cancer; ductal breast carcinoma in situ; progesterone receptor-positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RTOG-1005; NCI-2011-02669 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000700069