Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery

Stage II Breast Cancer Clinical Trial

Official title:

A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01872975
• Other study ID #: NSABP-B-51
• Secondary ID: NCI-2012-03198U1
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 2013
• Est. completion date: August 2028

Study information

• Verified date: December 2023
• Source: NSABP Foundation Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

Description:

PRIMARY OBJECTIVES:

To evaluate whether the addition of chest wall + regional nodal radiation therapy (XRT) after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for invasive breast cancer recurrence-free interval (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly prolong overall survival (OS) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

II. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rates of events for local-regional recurrence-free interval (LRRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

III. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for distant recurrence-free interval (DRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

IV. To compare the rates of disease-free survival (DFS)-ductal carcinoma in situ (DCIS) by treatment arm.

V. To compare the rates of second primary cancer (SPC) by treatment arm.

VI. To compare the effect of adding XRT on the cosmetic outcomes in mastectomy patients who have had reconstruction.

VII. To compare the effect of adding XRT on quality of life including arm problems, lymphedema, pain, and fatigue.

VIII. To evaluate the toxicity associated with each of the radiation therapy regimens.

IX. To determine whether computed tomography (CT)-based conformal methods (intensity-modulated radiation therapy [IMRT] and 3-dimensional conformal radiation therapy [3DCRT]) for chestwall + regional nodal XRT post mastectomy and regional nodal XRT with breast XRT following breast conserving surgery are feasible in a multi-institutional setting and whether dose-volume analyses can be established to assess treatment adequacy and to develop normal tissue complication probabilities (NTCP) for the likelihood of toxicity.

X. To compare the effect of XRT in patients receiving mastectomy and in patients receiving lumpectomy.

XI. To examine the role of proliferation measures as a prognosticator for patients with residual disease after neoadjuvant chemotherapy.

XII. To develop predictors of the degree of reduction in local regional recurrence (LRR).

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

ARM 1: Patients are assigned to 1 of 2 treatment groups.

GROUP 1A: Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

GROUP 1B: Mastectomy patients do not undergo radiation therapy.

ARM 2: Patients are assigned to 1 of 2 treatment groups.

GROUP 2A: Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

GROUP 2B: Mastectomy patients undergo regional nodal radiation therapy and chestwall XRT using IMRT or 3DCRT once daily 5 days a week for 5 weeks.

All patients also receive systemic therapy as planned (hormonal therapy for patients with hormone-receptor positive breast cancer and trastuzumab or other anti-human epidermal growth factor receptor 2 [HER2] therapy for patients with breast cancer that is HER2-positive).

After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months and then yearly for 8 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1636
• Est. completion date: August 2028
• Est. primary completion date: September 14, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines

• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before neoadjuvant therapy); clinical axillary nodal involvement can be assessed by palpation, ultrasound, CT scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, or PET/CT scan

• Patient must have had pathologic confirmation of axillary nodal involvement at presentation (before neoadjuvant therapy) based on either a positive fine needle aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy (demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be performed either by palpation or by image guidance; documentation of axillary nodal positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted

• Patients must have had estrogen receptor (ER) analysis performed on the primary breast tumor before neoadjuvant therapy 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 progesterone receptor (PgR) must also be performed according to current ASCO/CAP guideline recommendations for hormone receptor testing (http://www.asco.org)

• Patients must have had HER2 testing performed on the primary breast tumor before neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations for human epidermal growth factor receptor 2 testing in Breast Cancer (http://www.asco.org); patients who have a primary tumor that is either HER2-positive or HER2-negative are eligible

• Patient must have completed a minimum of 8 weeks of standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen

• For patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks of intended chemotherapy may be administered but must be completed before randomization; (if treatment delays occur, chemotherapy must be completed within 14 weeks); the dose and schedule of the adjuvant chemotherapy are at the investigator's discretion; Note: It is preferred that all intended chemotherapy be administered in the neoadjuvant setting

• Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless medically contraindicated

• At the time of definitive surgery, all removed axillary nodes must be histologically free from cancer; acceptable procedures for assessment of axillary nodal status at the time of surgery include:

• Axillary node dissection

• Sentinel node biopsy alone or

• Sentinel node biopsy followed by axillary node dissection

• Note: Patients are eligible whether there is residual invasive carcinoma in the surgical breast specimen or whether there is evidence of pathologic complete response; patients who are found to be pathologically node-positive at the time of surgery, based on sentinel node biopsy alone, are candidates for A011202, a study developed by the Alliance in Oncology, an NCI Cooperative Group; if A011202 is open at the investigator's institution, patients should be approached about participating in the A011202 study

• Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible (Note:

Postneoadjuvant therapy is designated with a "yp" prefix.)

• Patient who have undergone either a total mastectomy or a lumpectomy are eligible

• For patients who undergo lumpectomy, the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS as determined by the local pathologist; additional operative procedures may be performed to obtain clear margins; if tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible; (patients with margins positive for lobular carcinoma in situ [LCIS] are eligible without additional resection)

• For patients who undergo mastectomy, the margins must be histologically free of residual (microscopic or gross) tumor

• The interval between the last surgery for breast cancer (including re-excision of margins) and randomization must be no more than 70 days; also, if adjuvant chemotherapy was administered, the interval between the last chemotherapy treatment and randomization must be no more than 70 days

• The patient must have recovered from surgery with the incision completely healed and no signs of infection

• If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may interfere with delivery of radiation therapy should have resolved

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease

• T4 tumors including inflammatory breast cancer

• Documentation of axillary nodal positivity before neoadjuvant therapy by sentinel node biopsy alone

• N2 or N3 disease detected clinically or by imaging

• Patients with histologically positive axillary nodes post neoadjuvant therapy

• Patients with microscopic positive margins after definitive surgery

• Synchronous or previous contralateral invasive breast cancer or DCIS; (patients with synchronous and/or previous contralateral LCIS are eligible)

• Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy; (patients with synchronous or previous ipsilateral LCIS are eligible)

• History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization

• Any radiation therapy for the currently diagnosed breast cancer prior to randomization

• Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy; patients are eligible if these medications are discontinued prior to randomization

• Prior breast or thoracic radiation therapy (RT) for any condition

• Active collagen vascular disease, specifically dermatomyositis with a creatinine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosus, or scleroderma

• Pregnancy or lactation at the time of study entry; (Note: Pregnancy testing must be performed within 2 weeks prior to randomization according to institutional standards for women of childbearing potential)

• Other non-malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up

• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements

Related Conditions & MeSH terms

• Breast Neoplasms
• Stage IB Breast Cancer
• Stage II Breast Cancer

Intervention

Radiation:
• regional nodal XRT

• chestwall XRT

• WBI

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CIUSSSEMTL-Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Ireland	Saint Lukes Hospital	Dublin	Co Dublin
Ireland	University College Hospital Galway	Galway	Co Galway
Israel	Chaim Sheba Medical Center	Tel Hashomer
Japan	Hyogo Cancer Center	Akashi-city	Hyogo
Japan	Gunma University Hospital	Gunma	Maebashi
Japan	Shikoku Cancer Center	Matsuyama
Japan	Iwate Medical University School of Medicine	Morioka	Iwate
Japan	Niigata University Medical and Dental Hospital	Niigata City	Niigata
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Tohoku University School of Medicine	Sendai	Aoba-ku
Korea, Republic of	Yonsei University Health System-Severance Hospital	Seoul
Puerto Rico	San Juan City Hospital	San Juan
United States	The Cancer Center of Hawaii-Leeward	'Ewa Beach	Hawaii
United States	Texas Cancer Center	Abilene	Texas
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota
United States	Lovelace Radiation Oncology	Albuquerque	New Mexico
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Inova Alexandria Hospital	Alexandria	Virginia
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Florida Hospital Cancer Institute Altamonte	Altamonte Springs	Florida
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Fox Valley Surgical Associates Limited	Appleton	Wisconsin
United States	Radiology Associates of Appleton/ThedaCare Regional Medical Center	Appleton	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Texas Oncology-Arlington South	Arlington	Texas
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	John Fitzgerald Kennedy Medical Center	Atlantis	Florida
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Texas Oncology - Central Austin Cancer Center	Austin	Texas
United States	Texas Oncology - South Austin Cancer Center	Austin	Texas
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Texas Oncology Bedford	Bedford	Texas
United States	Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Overlake Hospital Medical Center	Bellevue	Washington
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Harrison Medical Center	Bremerton	Washington
United States	Ocean Medical Center	Brick	New Jersey
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Henry Ford Cancer Institute¿Downriver	Brownstown	Michigan
United States	Mills - Peninsula Hospitals	Burlingame	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Aultman Health Foundation	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Putnam Hospital Center	Carmel	New York
United States	Tanner Medical Center/Carrollton	Carrollton	Georgia
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Geaugra Hospital	Chardon	Ohio
United States	Bon Secours Saint Francis Hospital	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Roper Hospital	Charleston	South Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute-Pineville	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute-University	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	21st Century Oncology-Clarkston	Clarkston	Michigan
United States	Morton Plant Hospital	Clearwater	Florida
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Memorial Hospital Colorado Springs	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	Concord Hospital	Concord	New Hampshire
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Mary Bird Cancer Center/Saint Tammany Parish	Covington	Louisiana
United States	Barnes-Jewish West County Hospital	Creve Coeur	Missouri
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Dekalb Medical Center	Decatur	Georgia
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Epic Care-Dublin	Dublin	California
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Saint Elizabeth Medical Center South	Edgewood	Kentucky
United States	The Shaw Regional Cancer Center	Edwards	Colorado
United States	AMITA Health Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	The Regional Cancer Center	Erie	Pennsylvania
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Saint Anne's Hospital	Fall River	Massachusetts
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Virginia Mason Federal Way Medical Center	Federal Way	Washington
United States	Augusta Health Cancer Center	Fishersville	Virginia
United States	Vassar Brothers Fishkill Radiation Oncology Center	Fishkill	New York
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Texas Oncology-Flower Mound	Flower Mound	Texas
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Saint Elizabeth Fort Thomas	Fort Thomas	Kentucky
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	The Klabzuba Cancer Center	Fort Worth	Texas
United States	Mary Washington Hospital	Fredericksburg	Virginia
United States	California Cancer Center - North Fresno	Fresno	California
United States	Unity Hospital	Fridley	Minnesota
United States	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania
United States	University of Florida	Gainesville	Florida
United States	CaroMont Regional Medical Center	Gastonia	North Carolina
United States	Georgetown Hospital System	Georgetown	South Carolina
United States	The West Clinic - Wolf River	Germantown	Tennessee
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington
United States	Arizona Breast Cancer Specialists-Gilbert	Gilbert	Arizona
United States	Tate Cancer Center	Glen Burnie	Maryland
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Sentara Cancer Institute at Sentara CarePlex Hospital	Hampton	Virginia
United States	PinnacleHealth Cancer Center-Community Campus	Harrisburg	Pennsylvania
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Advocate South Suburban Hospital	Hazel Crest	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	The Radiation Oncology Center-Hilton Head/Bluffton	Hilton Head Island	South Carolina
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	Mary Bird Perkins Cancer Center/Terrebonne General Medical Center	Houma	Louisiana
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson Regional Care Center-Katy	Houston	Texas
United States	Memorial Hermann Memorial City Medical Center	Houston	Texas
United States	The Methodist Hospital System	Houston	Texas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	The University of Kansas Cancer Center-North	Kansas City	Missouri
United States	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Tri-Cities Cancer Center	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Ulster Radiation Oncology Center	Kingston	New York
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	City of Hope Antelope Valley	Lancaster	California
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Sparrow Hospital	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
United States	Doctor's Hospital of Laredo	Laredo	Texas
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Condell Memorial Hospital	Libertyville	Illinois
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky
United States	Norton Suburban Hospital and Medical Campus	Louisville	Kentucky
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Texas Tech University Health Sciences Center-Lubbock	Lubbock	Texas
United States	University Medical Center	Lubbock	Texas
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Elliot Hospital	Manchester	New Hampshire
United States	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Matthews Radiation Oncology Center	Matthews	North Carolina
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Holy Redeemer Hospital and Medical Center	Meadowbrook	Pennsylvania
United States	Summa Health Center at Lake Medina	Medina	Ohio
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Baptist Hospital of Miami	Miami	Florida
United States	Jackson Memorial Hospital-Holtz Children's Hospital	Miami	Florida
United States	South Miami Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio
United States	Middlesex Hospital	Middletown	Connecticut
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Carolinas HealthCare System Union	Monroe	North Carolina
United States	Intercommunity Cancer Center	Monroeville	Pennsylvania
United States	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	Virtua Memorial	Mount Holly	New Jersey
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington
United States	Intermountain Medical Center	Murray	Utah
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	MD Anderson Regional Care Center-Bay Area	Nassau Bay	Texas
United States	Allegheny Valley Hospital	Natrona Heights	Pennsylvania
United States	Surgical Associates of Neenah SC	Neenah	Wisconsin
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Columbia University/Herbert Irving Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Hoag Memorial Hospital	Newport Beach	California
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Mayo Clinic Radiation Therapy-Northfield	Northfield	Minnesota
United States	Assarian Cancer Center	Novi	Michigan
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Owensboro Health Mitchell Memorial Cancer Center	Owensboro	Kentucky
United States	McLaren Cancer Institute-Owosso	Owosso	Michigan
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	Desert Regional Medical Center	Palm Springs	California
United States	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Huntington Memorial Hospital	Pasadena	California
United States	Capital Health Medical Center-Hopewell	Pennington	New Jersey
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Arizona Breast Cancer Specialists-Phoenix	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Texas Oncology-Plano West	Plano	Texas
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Compass Oncology Rose Quarter	Portland	Oregon
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Vassar Brothers Medical Center	Poughkeepsie	New York
United States	Radiation Oncology Associates Incorporated	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington
United States	Wheaton Franciscan Cancer Care - All Saints	Racine	Wisconsin
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Valley Hospital	Ridgewood	New Jersey
United States	Oncology and Hematology Associates of Southwest Virginia	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Pluta Cancer Center	Rochester	New York
United States	Rochester General Hospital	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Scott and White Healthcare Round Rock	Round Rock	Texas
United States	Texas Oncology - Round Rock Cancer Center	Round Rock	Texas
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter General Hospital	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Saint Helena Hospital	Saint Helena	California
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Anthony's Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center - Saint Peters	Saint Peters	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Naval Medical Center -San Diego	San Diego	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Christus Saint Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Arizona Breast Cancer Specialists-Scottsdale	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Texas Cancer Center-Sherman	Sherman	Texas
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	South Jordan Health Center	South Jordan	Utah
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Providence Hospital-Southfield Cancer Center	Southfield	Michigan
United States	Baptist Memorial Hospital-Desoto	Southhaven	Mississippi
United States	Sparta Cancer Treatment Center	Sparta	New Jersey
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Spokane Valley Cancer Center-Mayfair	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Memorial Medical Center	Springfield	Illinois
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	MD Anderson Regional Care Center-Sugar Land	Sugar Land	Texas
United States	Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	South Atlantic Radiation Oncology	Supply	North Carolina
United States	Arizona Center for Cancer Care-Surprise	Surprise	Arizona
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Mid-Columbia Medical Center/Celilo Cancer Center	The Dalles	Oregon
United States	MD Anderson Regional Care Center-The Woodlands	The Woodlands	Texas
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	21st Century Oncology-Troy	Troy	Michigan
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Arizona Oncology Associates-West Orange Grove	Tucson	Arizona
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	Sentara Virginia Beach General Hospital	Virginia Beach	Virginia
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Kent County Hospital	Warwick	Rhode Island
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Deke Slayton Cancer Center	Webster	Texas
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	The Alyce and Elmore Kraemer Cancer Care Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University Pointe	West Chester	Ohio
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Coastal Carolina Radiation Oncology	Wilmington	North Carolina
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Metro Health Hospital	Wyoming	Michigan
United States	WellSpan Health-York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
NSABP Foundation Inc	National Cancer Institute (NCI), Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada,  Ireland,  Israel,  Japan,  Korea, Republic of,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IBC-RFI		Time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer, assessed up to 10 years
Secondary	OS		Time from randomization to death from any cause, assessed up to 10 years
Secondary	LRRFI		Time from randomization to recurrence of primary cancer w/in breast or lymph nodes in ipsilateral axilla, infraclavicular fossa, or ipsilateral internal mammary chain w/out evidence distant disease, or death due to breast cancer, assessed up to 10 years
Secondary	DRFI		Time from randomization to the development of tumor in all areas beyond local or regional limits, or death due to breast cancer, assessed up to 10 years
Secondary	DFS-DCIS		Time from randomization to local recurrence post-mastectomy/in ipsilateral breast post-lumpectomy, regional/distant recurrence, contralateral disease, second primary cancer, or death from any cause prior to recurrence or SPC, assessed up to 10 years
Secondary	Time to SPC		Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 10 years
Secondary	Effect of radiation therapy on cosmetic outcome in mastectomy and lumpectomy patients as assessed by quality of life questionnaire		Assessed prior to randomization, 3 months or at end of RT, and 6, 12, and 24 months from randomization
Secondary	Frequencies of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		Up to 30 days after completion of study treatment
Secondary	Molecular predictors of recurrence	To test the prognostic role of gene expression profiles in residual tumor tissue and to develop predictors of the degree of reduction of loco-regional recurrence.	Tissue samples collected within 90 days after randomization