Testing Whether Treating Breast Cancer Metastases With Surgery or High-Dose Radiation Improves Survival

Anatomic Stage IV Breast Cancer AJCC v8 Clinical Trial

Official title:

A Phase IIR/III Trial of Standard of Care Therapy With or Without Stereotactic Body Radiotherapy (SBRT) and/or Surgical Ablation for Newly Oligometastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02364557
• Other study ID #: NRG-BR002
• Secondary ID: NCI-2014-01810NR
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: December 24, 2014
• Est. completion date: December 20, 2026

Study information

• Verified date: January 2024
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II/III trial studies how well standard of care therapy with stereotactic radiosurgery and/or surgery works and compares it to standard of care therapy alone in treating patients with breast cancer that has spread to one or two locations in the body (limited metastatic) that are previously untreated. Standard of care therapy comprising chemotherapy, hormonal therapy, biological therapy, and others may help stop the spread of tumor cells. Radiation therapy and/or surgery is usually only given with standard of care therapy to relieve pain; however, in patients with limited metastatic breast cancer, stereotactic radiosurgery, also known as stereotactic body radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue and surgery may be able to effectively remove the metastatic tumor cells. It is not yet known whether standard of care therapy is more effective with stereotactic radiosurgery and/or surgery in treating limited metastatic breast cancer.

Description:

PRIMARY OBJECTIVES:

I. Phase II: To determine whether ablation [through stereotactic body radiation therapy (SBRT) (stereotactic radiosurgery) and/or surgical resection of all known metastases] in oligometastatic breast cancer patients provides a sufficient signal for improved progression-free survival (PFS) to warrant full accrual to the Phase III portion of the trial.

II. Phase III: To determine whether ablation (through SBRT and/or surgical resection of all known metastases) in oligometastatic breast cancer patients significantly improves overall survival (OS).

SECONDARY OBJECTIVES:

I. To evaluate treated metastasis control according to tumor receptor status [estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)], use of chemotherapy, surgery versus (vs.) ablative therapy, and number of metastases.

II. To evaluate whether the addition of ablative metastasis directed therapy significantly reduces the number of distant recurrences (new metastases) in patients who progress according to tumor receptor status (ER, PR, HER-2); use of chemotherapy, and number of metastases.

III. To evaluate adverse events in patients who receive ablative metastasis-directed therapy to all known metastases in addition to standard medical therapy compared with those treated with standard medical therapy alone.

EXPLORATORY OBJECTIVE:

I. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout the radiation therapy processes, including imaging, simulation, target and critical structure definition, treatment planning, image guidance, and delivery.

TRANSLATIONAL RESEARCH OBJECTIVES:

I. To determine whether < 5 circulating tumor cells (CTCs) (per 7.5 ml of blood) is an independent prognostic (outcome) marker for improved PFS and OS in oligometastatic breast cancer.

II. To determine whether < 5 CTCs (per 7.5 ml of blood) is an independent predictive (response to therapy) marker for improved PFS and OS in oligometastatic breast cancer.

III. To determine whether eliminating CTCs (0/7.5 ml of blood in patients with at least 2 CTCs at registration) is both a prognostic and predictive marker for improved PFS and OS.

IV. To evaluate the prognostic and predictive properties of CTC count as a continuous measure of PFS and OS.

V. To store material for retrospective analysis of circulating tumor deoxyribonucleic acid (ctDNA).

VI. To store material for retrospective analysis of circulating micro-ribonucleic acid (RNA).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 129
• Est. completion date: December 20, 2026
• Est. primary completion date: December 20, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A patient cannot be considered eligible for this study unless all of the following conditions are met.

• Pathologically confirmed metastatic breast cancer

• Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis;

• Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification

• Number of allowable metastases:

• =< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:

• Peripheral lung

• Osseous (bone)

• Spine

• Central lung

• Abdominal-pelvic metastases (lymph node/adrenal gland)

• Liver

• Mediastinal/cervical lymph node

• All known disease amenable to metastasis-directed therapy with either SBRT or resection

• Note: Symptomatic bone metastasis are allowed if ablative therapy can be delivered

• Note: Sites for possible surgical excision include lung, liver, adrenal gland, bone, small intestine, large intestine, ovary, and amenable nodal disease sites

• Note: Surgical stabilization is allowed for a metastasis if it is followed by conventionally fractionated external beam radiotherapy

• Maximum diameter of individual metastasis in any dimension =< 5 cm

• There are no restrictions on distance between the metastases

• Patients must be registered within 365 days of the initial metastatic breast cancer diagnosis; first-line standard systemic therapy (chemotherapy, anti-endocrine therapy, anti-HER2, or other standard targeted therapy) for metastatic breast cancer must be given or planned to be given; if given before study entry, it cannot have exceeded a duration of 12 months at the time of registration (Note: sequencing of ablative therapy [surgery or SBRT] relative to systemic therapy, for patients randomized to Arm 2, is at the discretion of the treating physician)

• The primary tumor site must be controlled prior to registration

• For those who present with synchronous primary and oligometastatic disease, primary must be controlled prior to registration

• The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference For those who present with local recurrence and oligometastatic disease, local recurrence must be controlled prior to registration

• The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference

• Appropriate stage for study entry based on the following diagnostic workup:

• History/physical examination within 60 days prior to registration

• Clinical grade computed tomography (CT) scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT within 60 days prior to study registration

• Zubrod performance status =< 2 within 60 days prior to registration

• Blood cell count (CBC)/differential obtained within 60 days prior to registration on study

• Absolute neutrophil count (ANC) >= 500 cells/mm^3

• Platelets >= 50,000 cells/mm^3

• Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

• For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

• Patients with any of the following conditions are NOT eligible for this study.

• Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;

• Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; previous RT dose, date, fraction size, must be reported

• Metastases with indistinct borders making targeting not feasible

• Note: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician's judgment will be required

• Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)

• Metastases located within 3 cm of the previously irradiated structures:

• Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)

• Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)

• Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)

• Brainstem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)

• Whole lung previously irradiated with prior percent volume receiving greater than or equal to 20 Gy (V20Gy)> 30% (delivered in =< 3 Gy/fraction)

• Primary tumor irradiated with SBRT

• Metastasis irradiated with SBRT

• Brain metastases

• Exudative, bloody, or cytological proven malignant effusions

• 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 at the time of registration

• Pregnancy; lactating females must cease expression of milk prior to signing consent to be eligible

• Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a cluster of differentiation 4 (CD4) count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol

Related Conditions & MeSH terms

• Anatomic Stage IV Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer American Joint Committee on Cancer (AJCC) v8
• Breast Neoplasms
• Metastatic Breast Carcinoma
• Metastatic Malignant Neoplasm in the Bone
• Metastatic Malignant Neoplasm in the Liver
• Metastatic Malignant Neoplasm in the Lung
• Metastatic Malignant Neoplasm in the Lymph Nodes
• Metastatic Malignant Neoplasm in the Spine
• Neoplasms
• Neoplasms, Second Primary
• Prognostic Stage IV Breast Cancer AJCC v8

Intervention

Radiation:
• Stereotactic Body Radiotherapy
Patients receive 1, 3, or 5 fractions of radiation, beginning within 6 weeks of study entry. For metastases in the peripheral lung, patients receive a single fraction of 30 Gy or 3 fractions for a total of 45 Gy. For a single liver metastases, patients receive a single fraction of 30 Gy. For metastases in the abdominal-pelvic or liver (>1), patients receive 3 fractions for a total of 45 Gy. For metastases in the central lung or mediastinal/ cervical lymph nodes, patients receive 5 fractions for a total of 50 Gy. For spinal metastases, patients receive 1 fraction of 20 Gy. For non-spinal osseous metastases, patients receive 3 fractions for a total of 30 Gy. For thoracic/cervical spine metastases, patients receive 5 fractions for a total of 35 Gy.

Procedure:
• Surgery
All surgical resections will be approached with intent of an R0 resection (rendering the patient with no evidence of measureable disease and pathologic negative margin) and must occur within 6 weeks of study entry. Approach to surgery will be based upon the treating surgeon. An open, laparoscopic, or thorascopic approach is acceptable.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	The Research Institute of the McGill University Health Centre (MUHC)	Montreal	Quebec
Canada	Ottawa Hospital and Cancer Center-General Campus	Ottawa	Ontario
Korea, Republic of	Yonsei University Health System-Severance Hospital	Seoul
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
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	Ascension Saint Vincent Anderson	Anderson	Indiana
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Rex Hematology Oncology Associates-Cary	Cary	North Carolina
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Michigan Healthcare Professionals Clarkston	Clarkston	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Michigan Healthcare Professionals Farmington	Farmington Hills	Michigan
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Rex Hematology Oncology Associates-Garner	Garner	North Carolina
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
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	Self Regional Healthcare	Greenwood	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
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	M D Anderson Cancer Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Loyola University Medical Center	Maywood	Illinois
United States	Miami Cancer Institute	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Virtua Memorial	Mount Holly	New Jersey
United States	IU Health Ball Memorial Hospital	Muncie	Indiana
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	CTCA at Southeastern Regional Medical Center	Newnan	Georgia
United States	Ogden Regional Medical Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Owensboro Health Mitchell Memorial Cancer Center	Owensboro	Kentucky
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Arizona Center for Cancer Care-Peoria	Peoria	Arizona
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Rex Hematology Oncology Associates-Blue Ridge	Raleigh	North Carolina
United States	UNC Rex Cancer Center of Wakefield	Raleigh	North Carolina
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Renown Regional Medical Center	Reno	Nevada
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Naval Medical Center -San Diego	San Diego	California
United States	MaineHealth Cancer Care Center of York County	Sanford	Maine
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Christus Saint Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Saint Joseph's Medical Center	Stockton	California
United States	Novant Cancer Institute Radiation Oncology - Supply	Supply	North Carolina
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Lewis Hall Singletary Oncology Center	Thomasville	Georgia
United States	Community Medical Center	Toms River	New Jersey
United States	GenesisCare USA - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Reading Hospital	West Reading	Pennsylvania
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Novant Health Cancer Institute Radiation Oncology - Wilmington	Wilmington	North Carolina
United States	Novant Health New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (Phase II)	Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Median PFS is provided.	From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months, then every six months to five years, then annually. Maximum follow-up at time of analysis was 63 months.
Primary	Overall Survival (Phase III)	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored).	From randomization to last follow-up. Follow-up schedule: 3 mos after randomization and every 3 months to 24 months and then annually. Maximum follow-up at time of analysis was 63 months.
Secondary	Percentage of Participants With Treated Metastasis Progression on the SOC + Ablation Arm	Metastasis progression (failure) is defined as the clearance and subsequent recurrence or the development of new metastases in the treated area. Failure time is defined as time from randomization to the date of first failure, last contact when participant had a documented clinical assessment (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method. Two-year failure rates are provided here.	From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months. Two-year rates are provide here.
Secondary	Percentage of Participants With New Metastases	New metastases (failure) is defined as the appearance of any new metastases. Failure time is measured from randomization to the date of first failure, last contact when participant had a documented clinical assessment (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year failure rates are provided here	From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.
Secondary	Number of Patients by Highest Grade Adverse Event Reported	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. Follow-up schedule: Arm 1: 3 mos. after randomization / Arm 2: weekly during SBRT and the last day of SBRT; both arms: then every 3 mos. to 24 mos., then annually. Maximum follow-up at time of analysis was 63 months.
Secondary	Progression-free Survival in the Presence or Absence of Circulating Tumor Cells (CTCs)	The presence of CTCs is defined as = 5 CTCs (per 7.5ml of blood). Progression (failure) is defined as any of the following: progression of metastases, new metastases, or death. Progression-free survival (PFS) time is defined as time from randomization to the date of first progression, death, or last contact when participant had a documented clinical assessment (censored). PFS rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the groups, which is reported in the statistical analysis results. Two-year PFS rates are provided here	From randomization to last follow-up. Follow-up schedule: 3 months after randomization, every 3 months up to 24 months, every six months up to five years, then annually. Maximum follow-up at time of analysis was 63 months.Two-year rates are provided here.