De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)

Sponsor

NRG Oncology (Other)

Overall Status

Recruiting

CT.gov ID

NCT04852887

Collaborator

National Cancer Institute (NCI) (NIH)

1,670

Enrollment

397

Locations

Arms

240.8

Anticipated Duration (Months)

4.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.

Condition or Disease	Intervention/Treatment	Phase
Stage I Breast Cancer	Other: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane) Drug: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)	Phase 3

Detailed Description

Breast conservation therapy for early stage breast cancer has been an important achievement of oncology practice in the last half century and breast radiotherapy (RT) has been essential in its development. Several seminal randomized clinical trials conducted in the 1980's era demonstrated that breast radiotherapy following lumpectomy yielded overall survival outcomes equivalent to mastectomy for treatment of early stage invasive breast cancer leading to the National Institute of Health (NIH) Consensus Conference statement in 1991 supporting breast conservation treatment.This established lumpectomy with RT as an alternative to mastectomy and subsequently the rate of breast conservation for eligible breast cancer patients rose steadily. Shortly thereafter, investigators recognized that the toxicity, patient burden, and geographic barriers associated with the protracted treatment course for breast RT was a potential barrier to breast conservation utilization. Numerous phase III clinical trials were conducted randomizing women post lumpectomy to RT vs. observation aimed at identifying which cases did not derive a significant RT benefit. No such subsets of breast cancer patients were consistently identified, thereby solidifying the standard that breast conservation required both lumpectomy and RT. Two meta-analyses by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) in 2005 and 2011 further reinforced the value of breast RT post lumpectomy by examining the relationship of local recurrence and breast cancer mortality relative to the use of breast RT post lumpectomy. In each analysis, it found for axillary node negative breast cancer patients undergoing breast conservation a small but consistent increase in breast cancer mortality when breast radiotherapy was omitted. As a result, breast RT after lumpectomy has become an established paradigm for breast conservation for early stage breast cancer and is recommended by the NCCN 2018 guidelines (as it has for nearly two decades) that are commonly used today by clinicians and health systems alike. The landscape of early stage breast cancer has changed dramatically over the past three decades since the establishment of breast conservation. Widespread screening with mammography has led to the diagnosis of smaller and earlier stage disease. All breast cancers are now routinely characterized by their hormone sensitivity based on the presence of estrogen and progesterone receptors on tumor cells within the biopsy or surgical specimen and presence of HER2 (human epidermal growth factor receptor 2) which has provided an additional means of stratifying breast cancer into distinct prognostic groups. Small, node negative invasive breast cancer that is hormone sensitive (HS) and HER2-negative has a lower overall recurrence rate (local, regional, and distant) than breast cancers characterized by more adverse clinical pathologic features. However, other than in a smaller subset of women greater than 70 years old, clinical trials in this HS population still demonstrated unacceptable local recurrence risks long term after lumpectomy alone emphasizing that clinical and pathologic features are insufficient for consistently identifying when RT can safely be omitted.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1670 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer

Actual Study Start Date :

Jun 7, 2021

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jul 1, 2041

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: Breast Radiation Therapy + Endocrine Therapy Radiation therapy to the breast and hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily	Other: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane) Post lumpectomy radiation therapy will be external beam radiation to either the whole breast + boost, partial breast irradiation, or Accelerated Partial Breast Irradiation that must begin within 12 weeks of the last breast cancer surgery(including re-excision of margins). Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s). Endocrine therapy may be initiated before, during, or after completion of radiation therapy at the discretion of the investigator.
Active Comparator: Arm 2: No Breast Radiation Therapy + Endocrine Therapy No radiation therapy, only hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily	Drug: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane) Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s).

Arm

Intervention/Treatment

Active Comparator: Arm 1: Breast Radiation Therapy + Endocrine Therapy

Radiation therapy to the breast and hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily

Other: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)

Post lumpectomy radiation therapy will be external beam radiation to either the whole breast + boost, partial breast irradiation, or Accelerated Partial Breast Irradiation that must begin within 12 weeks of the last breast cancer surgery(including re-excision of margins). Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s). Endocrine therapy may be initiated before, during, or after completion of radiation therapy at the discretion of the investigator.

Active Comparator: Arm 2: No Breast Radiation Therapy + Endocrine Therapy

No radiation therapy, only hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily

Drug: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)

Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s).

Outcome Measures

Primary Outcome Measures

Time to invasive or noninvasive IBTR. [5 years]
Time from randomization to any invasive or noninvasive IBTR or last follow-up (expressed as % IBTR-free)

Secondary Outcome Measures

Percent of women with an intact index breast at report of the primary endpoint inclusive of salvage second breast conservation procedures. [Through study completion, an average of 15 years.]
Time from randomization to any breast procedure after the initial surgery or last follow-up (expressed as % with intact index breast)
Time from randomization to the first occurrence of invasive ipsilateral breast tumor recurrence. [5 years]
Time from randomization to any invasive IBTR or last follow-up (expressed as percentage of invasive IBTR-free
Time from randomization to diagnosis of a local, regional or distant recurrence as a first cancer event. [5 years]
Time from randomization to any breast cancer recurrence at a local, regional or distant site or last follow-up (expressed as percentage of recurrence-free)
Time from randomization to the first distant cancer event (either a recurrence or a secondary primary cancer). [5 years]
Time from randomization to any cancer occurring at a distant site or last follow-up (expressed as percentage of distant disease-free)
Time from randomization to any death. [5 years]
Time from randomization to any death or last follow-up (expressed as percent surviving)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
The patient must have an ECOG performance status of 0 or 1.
The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection.)
The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
The following staging criteria must be met postoperatively according to AJCC 8th edition criteria: By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm).

By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible.)

Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen.

** For patients with a T1a tumor (less than or equal to 0.5 cm in size) who do not already have an Oncotype DX Recurrence Score at study entry, a specimen (unstained blocks or slides) must be sent to the Genomic Health centralized laboratory.

The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with greater than or equal to 1% ER or PgR staining by IHC are considered positive.
The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
Patients may be premenopausal or postmenopausal at the time of study entry. For study purposes, postmenopausal is defined as: Age 56 or older with no spontaneous menses for at least 12 months prior to study entry; or a documented hysterectomy; or Age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) and with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standard; or Documented bilateral oophorectomy.
The interval between the last surgery for breast cancer (including re-excision of margins) and study entry must be no more than 70 days.
The patient must have recovered from surgery with the incision completely healed and no signs of infection.
Bilateral mammogram or MRI within 6 months prior to study entry. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients must be intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or aromatase inhibitor). The specific regimen of endocrine therapy is at the treating physician's discretion.

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease.
pT2 - pT4 tumors including inflammatory breast cancer.
Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
Patient had a mastectomy.
Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
Non-epithelial breast malignancies such as sarcoma or lymphoma.
Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible.)
Paget's disease of the nipple.
Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)
Surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re- excision, the patient is eligible.)
Treatment plan that includes regional nodal irradiation.
Any treatment with radiation therapy, chemotherapy, biotherapy, and/or endocrine therapy administered for the currently diagnosed breast cancer prior to study entry.

(Short course endocrine therapy of less than 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18.)

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 study entry.
Current therapy with any endocrine therapy such as raloxifene (Evista®), tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Short course endocrine therapy of < 6 weeks duration is acceptable post core biopsy pre surgery if the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than or equal to 18.)
Patients intending to continue on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible. Patients that discontinue oral, transdermal, or subdermal estrogen replacement prior to registration are eligible.
Prior breast or thoracic RT for any condition.
Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
Pregnancy or lactation at the time of study entry or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for women of childbearing potential must be performed within 2 weeks prior to study entry.)
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of study therapy or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements or interfere with interpretation of study results.
Use of any investigational product within 30 days prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Cancer Center at Saint Joseph's	Phoenix	Arizona	United States	85004
3	Mayo Clinic Hospital in Arizona	Phoenix	Arizona	United States	85054
4	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
6	PCR Oncology	Arroyo Grande	California	United States	93420
7	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
8	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
9	Mercy Cancer Center �� Carmichael	Carmichael	California	United States	95608
10	Mercy San Juan Medical Center	Carmichael	California	United States	95608
11	Kaiser Permanente Dublin	Dublin	California	United States	94568
12	Mercy Cancer Center - Elk Grove	Elk Grove	California	United States	95758
13	Kaiser Permanente-Fremont	Fremont	California	United States	94538
14	Washington Hospital	Fremont	California	United States	94538
15	Fresno Cancer Center	Fresno	California	United States	93720
16	Kaiser Permanente-Fresno	Fresno	California	United States	93720
17	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
18	Kaiser Permanente-Modesto	Modesto	California	United States	95356
19	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
20	Kaiser Permanente-Oakland	Oakland	California	United States	94611
21	Saint Joseph Hospital - Orange	Orange	California	United States	92868
22	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
23	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
24	Kaiser Permanente- Marshall Medical Offices	Redwood City	California	United States	94063
25	Kaiser Permanente-Richmond	Richmond	California	United States	94801
26	Mercy Cancer Center - Rocklin	Rocklin	California	United States	95765
27	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
28	Kaiser Permanente-Roseville	Roseville	California	United States	95661
29	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
30	Kaiser Permanente Downtown Commons	Sacramento	California	United States	95814
31	Mercy Cancer Center - Sacramento	Sacramento	California	United States	95816
32	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
33	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
34	South Sacramento Cancer Center	Sacramento	California	United States	95823
35	Saint Helena Hospital	Saint Helena	California	United States	94574
36	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
37	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
38	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
39	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
40	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California	United States	93401
41	Kaiser San Rafael-Gallinas	San Rafael	California	United States	94903
42	Ridley-Tree Cancer Center	Santa Barbara	California	United States	93105
43	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
44	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California	United States	93444
45	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
46	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
47	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
48	Kaiser Permanente-Stockton	Stockton	California	United States	95210
49	Torrance Memorial Physician Network - Cancer Care	Torrance	California	United States	90505
50	Torrance Memorial Medical Center	Torrance	California	United States	90509
51	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
52	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
53	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
54	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
55	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
56	Woodland Memorial Hospital	Woodland	California	United States	95695
57	University of Colorado Hospital	Aurora	Colorado	United States	80045
58	Saint Francis Cancer Center	Colorado Springs	Colorado	United States	80923
59	UCHealth - Cherry Creek	Denver	Colorado	United States	80206
60	Porter Adventist Hospital	Denver	Colorado	United States	80210
61	Shaw Cancer Center	Edwards	Colorado	United States	81632
62	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
63	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado	United States	80528
64	UCHealth Greeley Hospital	Greeley	Colorado	United States	80631
65	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado	United States	80129
66	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
67	Medical Center of the Rockies	Loveland	Colorado	United States	80538
68	Parker Adventist Hospital	Parker	Colorado	United States	80138
69	Beebe South Coastal Health Campus	Frankford	Delaware	United States	19945
70	Beebe Medical Center	Lewes	Delaware	United States	19958
71	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
72	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
73	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
74	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
75	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
76	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
77	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
78	GenesisCare USA - Aventura FP	Aventura	Florida	United States	33180
79	GenesisCare USA - Aventura	Aventura	Florida	United States	33180
80	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida	United States	33180
81	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida	United States	33146
82	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
83	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida	United States	33905
84	The Watson Clinic	Lakeland	Florida	United States	33805
85	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
86	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
87	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
88	GenesisCare USA - Plantation	Plantation	Florida	United States	33324
89	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
90	Cleveland Clinic-Weston	Weston	Florida	United States	33331
91	Northside Hospital-Alpharetta	Alpharetta	Georgia	United States	30005
92	Piedmont Hospital	Atlanta	Georgia	United States	30309
93	Northside Hospital	Atlanta	Georgia	United States	30342
94	Northside Hospital-Cherokee	Canton	Georgia	United States	30115
95	Northside Hospital-Forsyth	Cumming	Georgia	United States	30041
96	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
97	Piedmont Newnan Hospital	Newnan	Georgia	United States	30265
98	Piedmont Henry Hospital	Stockbridge	Georgia	United States	30281
99	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
100	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
101	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
102	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
103	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
104	Carle on Vermilion	Danville	Illinois	United States	61832
105	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
106	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
107	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
108	Crossroads Cancer Center	Effingham	Illinois	United States	62401
109	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
110	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
111	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
112	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
113	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
114	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
115	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
116	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
117	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
118	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
119	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
120	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
121	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
122	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
123	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
124	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
125	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
126	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
127	Carle Cancer Center	Urbana	Illinois	United States	61801
128	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
129	Illinois CancerCare - Washington	Washington	Illinois	United States	61571
130	Mary Greeley Medical Center	Ames	Iowa	United States	50010
131	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
132	Saint Luke's Hospital	Cedar Rapids	Iowa	United States	52402
133	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
134	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
135	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas	United States	66211
136	Salina Regional Health Center	Salina	Kansas	United States	67401
137	University of Kansas Health System Saint Francis Campus	Topeka	Kansas	United States	66606
138	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
139	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
140	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
141	Ochsner Hematology Oncology North Shore - Covington (West Region)	Covington	Louisiana	United States	70433
142	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
143	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
144	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
145	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
146	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
147	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
148	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
149	MedStar Good Samaritan Hospital	Baltimore	Maryland	United States	21239
150	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland	United States	21044
151	University of Maryland Shore Medical Center at Easton	Easton	Maryland	United States	21601
152	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland	United States	21061
153	Kaiser Permanente - Largo Medical Center	Largo	Maryland	United States	20774
154	Lowell General Hospital	Lowell	Massachusetts	United States	01854
155	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
156	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
157	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
158	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
159	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan	United States	48114
160	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan	United States	48183
161	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
162	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan	United States	48188
163	Caro Cancer Center	Caro	Michigan	United States	48723
164	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
165	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan	United States	48118
166	GenesisCare USA - Clarkston	Clarkston	Michigan	United States	48346
167	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
168	Henry Ford Medical Center-Fairlane	Dearborn	Michigan	United States	48126
169	Henry Ford Hospital	Detroit	Michigan	United States	48202
170	GenesisCare USA - Farmington Hills	Farmington Hills	Michigan	United States	48334
171	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan	United States	48336
172	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
173	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
174	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
175	Allegiance Health	Jackson	Michigan	United States	49201
176	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
177	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
178	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
179	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
180	GenesisCare USA - Macomb	Macomb	Michigan	United States	48044
181	GenesisCare USA - Madison Heights	Madison Heights	Michigan	United States	48071
182	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan	United States	48453
183	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
184	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan	United States	49444
185	Henry Ford Medical Center-Columbus	Novi	Michigan	United States	48377
186	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
187	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
188	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
189	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
190	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
191	Ascension Saint Joseph Hospital	Tawas City	Michigan	United States	48764
192	Munson Medical Center	Traverse City	Michigan	United States	49684
193	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
194	GenesisCare USA - Troy	Troy	Michigan	United States	48098
195	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
196	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
197	Metro Health Hospital	Wyoming	Michigan	United States	49519
198	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan	United States	48197
199	Mayo Clinic Health System in Albert Lea	Albert Lea	Minnesota	United States	56007
200	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
201	Minnesota Oncology - Burnsville	Burnsville	Minnesota	United States	55337
202	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
203	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
204	Unity Hospital	Fridley	Minnesota	United States	55432
205	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota	United States	56001
206	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota	United States	55369
207	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
208	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
209	Health Partners Inc	Minneapolis	Minnesota	United States	55454
210	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
211	Regions Hospital	Saint Paul	Minnesota	United States	55101
212	United Hospital	Saint Paul	Minnesota	United States	55102
213	Lakeview Hospital	Stillwater	Minnesota	United States	55082
214	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
215	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
216	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
217	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
218	Freeman Health System	Joplin	Missouri	United States	64804
219	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
220	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri	United States	64064
221	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri	United States	64116
222	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
223	Mercy Hospital South	Saint Louis	Missouri	United States	63128
224	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
225	Billings Clinic Cancer Center	Billings	Montana	United States	59101
226	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
227	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
228	OptumCare Cancer Care at Seven Hills	Henderson	Nevada	United States	89052
229	OptumCare Cancer Care at Charleston	Las Vegas	Nevada	United States	89102
230	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
231	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
232	OptumCare Cancer Care at MountainView	Las Vegas	Nevada	United States	89128
233	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
234	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
235	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
236	Renown Regional Medical Center	Reno	Nevada	United States	89502
237	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
238	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
239	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
240	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
241	Capital Health Medical Center-Hopewell	Pennington	New Jersey	United States	08534
242	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
243	Northwell Health Imbert Cancer Center	Bay Shore	New York	United States	11706
244	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
245	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
246	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
247	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
248	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
249	Mary Imogene Bassett Hospital	Cooperstown	New York	United States	13326
250	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
251	Glens Falls Hospital	Glens Falls	New York	United States	12801
252	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
253	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
254	NYU Winthrop Hospital	Mineola	New York	United States	11501
255	Northern Westchester Hospital	Mount Kisco	New York	United States	10549
256	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
257	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
258	Upstate Cancer Center at Oswego	Oswego	New York	United States	13126
259	Phelps Memorial Hospital Center	Sleepy Hollow	New York	United States	10591
260	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
261	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
262	SUNY Upstate Medical Center-Community Campus	Syracuse	New York	United States	13215
263	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
264	Atrium Health Stanly/LCI-Albemarle	Albemarle	North Carolina	United States	28002
265	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
266	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
267	Atrium Health Pineville/LCI-Pineville	Charlotte	North Carolina	United States	28210
268	Atrium Health University City/LCI-University	Charlotte	North Carolina	United States	28262
269	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina	United States	28025
270	Levine Cancer Institute - Rutherford	Forest City	North Carolina	United States	28043
271	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina	United States	27284
272	Matthews Radiation Oncology Center	Matthews	North Carolina	United States	28105
273	Atrium Health Union/LCI-Union	Monroe	North Carolina	United States	28112
274	CarolinaEast Medical Center	New Bern	North Carolina	United States	28561
275	Atrium Health Cleveland/LCI-Cleveland	Shelby	North Carolina	United States	28150
276	Novant Health Cancer Institute - Thomasville	Thomasville	North Carolina	United States	27360
277	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
278	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
279	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
280	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
281	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
282	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
283	Summa Health System - Barberton Campus	Barberton	Ohio	United States	44203
284	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	United States	44122
285	Cleveland Clinic Mercy Hospital	Canton	Ohio	United States	44708
286	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio	United States	45219
287	Case Western Reserve University	Cleveland	Ohio	United States	44106
288	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
289	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
290	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
291	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
292	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio	United States	45415
293	Miami Valley Hospital North	Dayton	Ohio	United States	45415
294	Armes Family Cancer Center	Findlay	Ohio	United States	45840
295	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
296	Orion Cancer Care	Findlay	Ohio	United States	45840
297	Mount Carmel Grove City Hospital	Grove City	Ohio	United States	43123
298	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio	United States	44906
299	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
300	Summa Health Medina Medical Center	Medina	Ohio	United States	44256
301	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
302	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio	United States	44130
303	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
304	University Hospitals Portage Medical Center	Ravenna	Ohio	United States	44266
305	North Coast Cancer Care	Sandusky	Ohio	United States	44870
306	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
307	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
308	South Pointe Hospital	Warrensville Heights	Ohio	United States	44122
309	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio	United States	45069
310	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
311	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
312	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
313	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
314	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
315	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
316	Providence Portland Medical Center	Portland	Oregon	United States	97213
317	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
318	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
319	Oregon Health and Science University	Portland	Oregon	United States	97239
320	Crozer-Keystone Regional Cancer Center at Broomall	Broomall	Pennsylvania	United States	19008
321	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
322	Ephrata Cancer Center	Ephrata	Pennsylvania	United States	17522
323	Saint Vincent Hospital	Erie	Pennsylvania	United States	16544
324	Adams Cancer Center	Gettysburg	Pennsylvania	United States	17325
325	Crozer Regional Cancer Center at Brinton Lake	Glen Mills	Pennsylvania	United States	19342
326	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
327	Jefferson Hospital	Jefferson Hills	Pennsylvania	United States	15025
328	Sechler Family Cancer Center	Lebanon	Pennsylvania	United States	17042
329	Yolanda G Barco Oncology Institute	Meadville	Pennsylvania	United States	16335
330	Forbes Hospital	Monroeville	Pennsylvania	United States	15146
331	Allegheny Valley Hospital	Natrona Heights	Pennsylvania	United States	15065
332	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
333	Jefferson Torresdale Hospital	Philadelphia	Pennsylvania	United States	19114
334	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
335	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
336	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania	United States	15090
337	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania	United States	19090
338	WellSpan Health-York Cancer Center	York	Pennsylvania	United States	17403
339	WellSpan Health-York Hospital	York	Pennsylvania	United States	17403
340	Rhode Island Hospital	Providence	Rhode Island	United States	02903
341	Women and Infants Hospital	Providence	Rhode Island	United States	02905
342	Kent Hospital	Warwick	Rhode Island	United States	02886
343	Medical University of South Carolina	Charleston	South Carolina	United States	29425
344	Tidelands Georgetown Memorial Hospital	Georgetown	South Carolina	United States	29440
345	Rock Hill Radiation Therapy Center	Rock Hill	South Carolina	United States	29730
346	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina	United States	29732
347	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
348	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
349	Hendrick Medical Center	Abilene	Texas	United States	79601
350	MD Anderson in The Woodlands	Conroe	Texas	United States	77384
351	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
352	M D Anderson Cancer Center	Houston	Texas	United States	77030
353	MD Anderson West Houston	Houston	Texas	United States	77079
354	Doctor's Hospital of Laredo	Laredo	Texas	United States	78041
355	MD Anderson League City	League City	Texas	United States	77573
356	MD Anderson in Sugar Land	Sugar Land	Texas	United States	77478
357	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont	United States	05819
358	VCU Massey Cancer Center at Hanover Medical Park	Mechanicsville	Virginia	United States	23116
359	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
360	VCU Massey Cancer Center at Stony Point	Richmond	Virginia	United States	23235
361	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
362	VCU Community Memorial Health Center	South Hill	Virginia	United States	23970
363	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
364	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
365	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701
366	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
367	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
368	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
369	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
370	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
371	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
372	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
373	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
374	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
375	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
376	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
377	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin	United States	54601
378	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
379	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
380	Aspirus Medford Hospital	Medford	Wisconsin	United States	54451
381	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
382	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
383	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
384	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
385	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
386	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
387	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
388	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
389	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
390	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
391	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
392	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
393	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin	United States	53188
394	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
395	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
396	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
397	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin	United States	54494