Radiation Therapy With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer

Sponsor

Radiation Therapy Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00956007

Collaborator

National Cancer Institute (NCI) (NIH), NRG Oncology (Other)

703

Enrollment

264

Locations

Arms

201

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in treating patients who have undergone surgery for locally advanced head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: cetuximab Radiation: intensity-modulated radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

Determine whether the addition of cetuximab to postoperative intensity-modulated radiotherapy (IMRT) will improve overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck at intermediate risk following surgery.

Secondary

Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free survival (DFS) of these patients.
Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months.
Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII expression, as well as the association of these assay data with OS and DFS.
Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ hybridization), specifically, within the cohort of patients with oropharynx cancer, to perform an exploratory analysis of the impact of HPV on DFS and OS of this patient subset.
Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and prognosis.
Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of response to cetuximab.

Tertiary

Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional control.
Assess the impact of the addition of cetuximab to postoperative IMRT on patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on head and neck specific instruments, including the Performance Status Scale for Head and Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the Dermatology Life Quality Index (DLQI).
Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility analysis using the EuroQol (EQ-5D).
Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly XeQOLS scores).
Retrospectively compare the loco-regional control rate in patients treated with IMRT alone (no IGRT or cetuximab) with similar patients treated with external beam radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group (RTOG)-95 01.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T2-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 3, 12, and 24 months.

Tissue samples are collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

703 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer

Actual Study Start Date :

Nov 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I: Intensity-Modulated Radiotherapy Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.	Radiation: intensity-modulated radiation therapy Patients undergo radiotherapy.
Experimental: Arm II: IMRT plus cetuximab Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity.	Biological: cetuximab Given IV Radiation: intensity-modulated radiation therapy Patients undergo radiotherapy.

Arm

Intervention/Treatment

Active Comparator: Arm I: Intensity-Modulated Radiotherapy

Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Radiation: intensity-modulated radiation therapy

Patients undergo radiotherapy.

Experimental: Arm II: IMRT plus cetuximab

Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity.

Biological: cetuximab

Given IV

Radiation: intensity-modulated radiation therapy

Patients undergo radiotherapy.

Outcome Measures

Primary Outcome Measures

Overall survival [From randomization to date of death or last follow-up. Analysis occurs after 372 events have been reported.]

Secondary Outcome Measures

Adverse events (dysphagia, xerostomia, and skin toxicity) according to CTCAE, v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months [From start of treatment to 2 years after end of treatment.]
Other acute adverse events (≤ 90 days from start of radiotherapy [RT]) according to CTCAE, v. 4 [From start of treatment to 90 days.]
Other late adverse events (> 90 days from start of RT) according to CTCAE, v. 4 [From 90 days after start of treatment to last follow-up.]
Disease-free survival [From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome.]
Loco-regional control [From randomization to date of failure (local or regional progression or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome.]
Quality of life as measured by Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) and EuroQol (EQ-5D) at baseline and at 3, 12, and 24 months [From randomization to 2 years.]
Xerostomia as measured by University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) at baseline and at 3, 12, and 24 months [From randomization to 2 years.]
Swallowing as measured by the normalcy of diet subscale of the Performance Status Scale for Head and Neck Cancer (PSS-HN) at baseline and at 3, 12, and 24 months [From randomization to 2 years.]
Skin toxicity as measured by the Dermatology Life Quality Index (DLQI) at baseline and at 3, 12, and 24 months [From randomization to 2 years.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma (including variants, such as verrucous carcinoma, spindle cell carcinoma, or carcinoma not otherwise specified) of the head and neck, including the following subtypes:
Oral cavity
Oropharynx
Larynx
Clinical stage T1, N1-2, M0 OR T2-4a, N0-2, M0 disease based on the following diagnostic workup within the past 8 weeks:
General history and physical examination by a Radiation Oncologist and/or Medical Oncologist
Chest x-ray or chest CT scan (with or without contrast) or chest CT/PET scan (with or without contrast)
Must have undergone gross total resection of the primary tumor with curative intent within the past 7 weeks with surgical pathology demonstrating ≥ 1 of the following criteria for "intermediate" risk of recurrence:
Perineural invasion
Lymphovascular invasion
Single lymph node > 3 cm or ≥ 2 lymph nodes (all < 6 cm) (no extracapsular extension)
Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins (similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible)
Pathologically confirmed T3 or T4a primary tumor
T2 oral cavity cancer with > 5 mm depth of invasion
No positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
Total bilirubin < 2 times upper limit of normal (ULN)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN
Serum creatinine < 2 times ULN OR creatinine clearance ≥ 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other invasive malignancy within the past 3 years, except for nonmelanomatous skin cancer or previously treated carcinoma in situ of the breast, oral cavity, or cervix
No simultaneous primary or bilateral tumors
No severe, active co-morbidity, including any of the following:
Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
Transmural myocardial infarction within the past 6 months
Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to have required oxygen therapy within the past year
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
AIDS based on current Centers for Disease Control (CDC) definition
Grade 3-4 electrolyte abnormalities according to CTCAE, v. 4, including any of the following:
Serum calcium (ionized or adjusted for albumin) < 7 mg/dL or > 12.5 mg/dL*
Glucose < 40 mg/dL or > 250 mg/dL
Magnesium < 0.9 mg/dL or > 3 mg/dL*
Potassium < 3.0 mmol/L or > 6 mmol/L*
Sodium < 130 mmol/L or > 155 mmol/L* NOTE: *Despite intervention to normalize levels.
No prior allergic reaction to cetuximab

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for this cancer
Prior chemotherapy or anti-EGF therapy for a different cancer allowed
No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
No concurrent amifostine as a radioprotector
No concurrent granulocyte colony-stimulating factor or erythropoietin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Arizona Oncology Associates-West Orange Grove	Tucson	Arizona	United States	85704
3	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
4	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
5	Mercy San Juan Medical Center	Carmichael	California	United States	95608
6	City of Hope	Duarte	California	United States	91010
7	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
8	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
9	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
10	University of Southern California/Norris Cancer Center	Los Angeles	California	United States	90033
11	Memorial Medical Center	Modesto	California	United States	95355
12	Bay Area Tumor Institute CCOP	Oakland	California	United States	94609
13	Pomona Valley Hospital Medical Center	Pomona	California	United States	91767
14	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
15	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
16	Sutter General Hospital	Sacramento	California	United States	95816
17	University of California at Davis Cancer Center	Sacramento	California	United States	95817
18	Mercy General Hospital Radiation Oncology Center	Sacramento	California	United States	95819
19	Saint Helena Hospital	Saint Helena	California	United States	94574
20	UCSF-Mount Zion	San Francisco	California	United States	94115
21	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
22	Stanford University Hospitals and Clinics	Stanford	California	United States	94305
23	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
24	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
25	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
26	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
27	Porter Adventist Hospital	Denver	Colorado	United States	80210
28	Swedish Medical Center	Englewood	Colorado	United States	80113
29	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
30	Saint Vincent's Medical Center	Bridgeport	Connecticut	United States	06606
31	Yale University	New Haven	Connecticut	United States	06520
32	William Backus Hospital	Norwich	Connecticut	United States	06360
33	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
34	University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
35	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
36	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
37	Baptist Hospital of Miami	Miami	Florida	United States	33176
38	Florida Hospital	Orlando	Florida	United States	32803
39	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
40	Emory University/Winship Cancer Institute	Atlanta	Georgia	United States	30322
41	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
42	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
43	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
44	Saint Joseph's-Candler Health System	Savannah	Georgia	United States	31405
45	Queen's Medical Center	Honolulu	Hawaii	United States	96813
46	University of Hawaii	Honolulu	Hawaii	United States	96813
47	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
48	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
49	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612-3785
50	University of Illinois	Chicago	Illinois	United States	60612
51	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
52	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
53	Hines Veterans Administration Hospital	Hines	Illinois	United States	60141
54	Loyola University Medical Center	Maywood	Illinois	United States	60153
55	Saint John's Hospital	Springfield	Illinois	United States	62702
56	Memorial Medical Center	Springfield	Illinois	United States	62781-0001
57	Carle Cancer Center	Urbana	Illinois	United States	61801
58	Radiation Oncology Associates PC	Fort Wayne	Indiana	United States	46804
59	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
60	IU Health Methodist Hospital	Indianapolis	Indiana	United States	46202
61	Community Regional Cancer Care-East Radiation Oncology	Indianapolis	Indiana	United States	46219
62	Community Regional Cancer Care-North	Indianapolis	Indiana	United States	46256
63	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
64	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
65	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
66	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
67	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
68	Siouxland Hematology Oncology Associates	Sioux City	Iowa	United States	51101
69	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
70	University of Kentucky	Lexington	Kentucky	United States	40536
71	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
72	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
73	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
74	Touro Infirmary	New Orleans	Louisiana	United States	70115
75	Central Maine Medical Center	Lewiston	Maine	United States	04240
76	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
77	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
78	Tufts Medical Center	Boston	Massachusetts	United States	02111
79	Boston Medical Center	Boston	Massachusetts	United States	02118
80	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
81	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
82	University of Michigan	Ann Arbor	Michigan	United States	48109
83	Oakwood Hospital	Dearborn	Michigan	United States	48124
84	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
85	Henry Ford Hospital	Detroit	Michigan	United States	48202
86	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
87	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
88	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
89	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
90	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
91	Saint Luke's Hospital of Duluth	Duluth	Minnesota	United States	55805
92	Unity Hospital	Fridley	Minnesota	United States	55432
93	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
94	Mayo Clinic	Rochester	Minnesota	United States	55905
95	Regions Hospital	Saint Paul	Minnesota	United States	55101
96	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
97	Singing River Hospital	Pascagoula	Mississippi	United States	39581
98	Cape Radiation Oncology	Cape Girardeau	Missouri	United States	63703
99	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
100	Kansas City Cancer Centers - North	Kansas City	Missouri	United States	64154
101	Kansas City Cancer Center-Lee's Summit	Lee's Summit	Missouri	United States	64064
102	Saint Louis University Hospital	Saint Louis	Missouri	United States	63110
103	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
104	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
105	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
106	Barnes-Jewish West County Hospital	Saint Louis	Missouri	United States	63141
107	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
108	Siteman Cancer Center - Saint Peters	Saint Peters	Missouri	United States	63376
109	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
110	CoxHealth South Hospital	Springfield	Missouri	United States	65807
111	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
112	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
113	The Nebraska Medical Center	Omaha	Nebraska	United States	68198
114	Renown Regional Medical Center	Reno	Nevada	United States	89502
115	Exeter Hospital	Exeter	New Hampshire	United States	03833
116	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
117	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States	07920
118	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
119	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey	United States	08060
120	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
121	UMDNJ - New Jersey Medical School	Newark	New Jersey	United States	07103
122	Sparta Cancer Treatment Center	Sparta	New Jersey	United States	07871
123	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
124	University of New Mexico	Albuquerque	New Mexico	United States	87106
125	New York Oncology Hematology PC - Albany	Albany	New York	United States	12206
126	Maimonides Medical Center	Brooklyn	New York	United States	11219
127	Sands Cancer Center	Canandaigua	New York	United States	14424
128	Memorial Sloan Kettering Cancer Center Commack	Commack	New York	United States	11725
129	Beth Israel Medical Center	New York	New York	United States	10003
130	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
131	Highland Hospital	Rochester	New York	United States	14620
132	University Radiation Oncology	Rochester	New York	United States	14626
133	University of Rochester	Rochester	New York	United States	14642
134	Memorial Sloan-Kettering Cancer Center Rockville Centre	Rockville Centre	New York	United States	11570
135	Memorial Sloan-Kettering Cancer Center at Sleepy Hallow	Sleepy Hollow	New York	United States	10591
136	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
137	University of North Carolina	Chapel Hill	North Carolina	United States	27599
138	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
139	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
140	Cancer Centers of North Carolina	Raleigh	North Carolina	United States	27607
141	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
142	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
143	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
144	Akron General Medical Center	Akron	Ohio	United States	44307
145	Summa Barberton Hospital	Barberton	Ohio	United States	44203
146	Mercy Medical Center	Canton	Ohio	United States	44708
147	Geaugra Hospital	Chardon	Ohio	United States	44024
148	University of Cincinnati	Cincinnati	Ohio	United States	45267
149	Case Western Reserve University	Cleveland	Ohio	United States	44106
150	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
151	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
152	Ohio State University Medical Center	Columbus	Ohio	United States	43210
153	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
154	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
155	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
156	Summa Health Center at Lake Medina	Medina	Ohio	United States	44256
157	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
158	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio	United States	44130
159	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio	United States	44122
160	Saint Charles Hospital	Oregon	Ohio	United States	43616
161	Robinson Radiation Oncology	Ravenna	Ohio	United States	44266
162	North Coast Cancer Care	Sandusky	Ohio	United States	44870
163	Cleveland Clinic Cancer Center-Strongsville	Strongsville	Ohio	United States	44136
164	Flower Hospital	Sylvania	Ohio	United States	43560
165	University Pointe	West Chester	Ohio	United States	45069
166	UHHS-Westlake Medical Center	Westlake	Ohio	United States	44145
167	Cleveland Clinic Wooster Specialty Center	Wooster	Ohio	United States	44691
168	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
169	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
170	Willamette Valley Cancer Center	Eugene	Oregon	United States	97401
171	Providence Portland Medical Center	Portland	Oregon	United States	97213
172	Western Oncology Research Consortium	Portland	Oregon	United States	97213
173	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
174	Oregon Health and Science University	Portland	Oregon	United States	97239
175	Portland Veterans Administration Medical Center	Portland	Oregon	United States	97239
176	Salem Hospital	Salem	Oregon	United States	97301
177	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
178	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
179	Northeast Radiation Oncology Center	Dunmore	Pennsylvania	United States	18512
180	Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
181	Adams Cancer Center	Gettysburg	Pennsylvania	United States	17325
182	Cherry Tree Cancer Center	Hanover	Pennsylvania	United States	17331
183	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania	United States	19047
184	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
185	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
186	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
187	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
188	Reading Hospital	West Reading	Pennsylvania	United States	19611
189	WellSpan Health-York Hospital	York	Pennsylvania	United States	17405
190	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
191	Medical University of South Carolina	Charleston	South Carolina	United States	29425
192	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
193	Greenville Health System Cancer Institute/Greenville CCOP	Greenville	South Carolina	United States	29615
194	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
195	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
196	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
197	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
198	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
199	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
200	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
201	Texas Oncology-Austin Midtown	Austin	Texas	United States	78705
202	Texas Oncology - Central Austin Cancer Center	Austin	Texas	United States	78731
203	Texas Oncology - South Austin Cancer Center	Austin	Texas	United States	78745
204	Texas Oncology PA - Bedford	Bedford	Texas	United States	76022
205	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
206	Texas Oncology-Denton South	Denton	Texas	United States	76210
207	The Klabzuba Cancer Center	Fort Worth	Texas	United States	76104
208	Memorial Hermann Memorial City Medical Center	Houston	Texas	United States	77024
209	Ben Taub General Hospital	Houston	Texas	United States	77030
210	M D Anderson Cancer Center	Houston	Texas	United States	77030
211	Texas Oncology-Seton Williamson	Round Rock	Texas	United States	78665
212	Texas Oncology - Round Rock Cancer Center	Round Rock	Texas	United States	78681
213	Cancer Care Centers of South Texas- Northeast	San Antonio	Texas	United States	78217
214	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
215	Texas Cancer Center-Sherman	Sherman	Texas	United States	75090
216	Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas	United States	77479
217	Texas Oncology-Wichita Falls Texoma Cancer Center	Wichita Falls	Texas	United States	76310
218	Intermountain Medical Center	Murray	Utah	United States	84157
219	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
220	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
221	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
222	LDS Hospital	Salt Lake City	Utah	United States	84143
223	University of Virginia	Charlottesville	Virginia	United States	22908
224	Sentara Cancer Institute at Sentara CarePlex Hospital	Hampton	Virginia	United States	23666
225	Sentara Hospitals	Norfolk	Virginia	United States	23507
226	Hunter Holmes McGuire Veterans Administration Medical Center	Richmond	Virginia	United States	23249
227	Virginia Commonwealth University	Richmond	Virginia	United States	23298
228	Sentara Virginia Beach General Hospital	Virginia Beach	Virginia	United States	23454
229	Harrison Medical Center	Bremerton	Washington	United States	98310
230	Tri-Cities Cancer Center	Kennewick	Washington	United States	99336
231	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
232	University of Washington Medical Center	Seattle	Washington	United States	98195
233	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
234	Cancer Care Northwest-North Spokane	Spokane	Washington	United States	99218
235	Northwest CCOP	Tacoma	Washington	United States	98405
236	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
237	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
238	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801
239	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
240	Wheeling Hospital	Wheeling	West Virginia	United States	26003
241	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
242	Fox Valley Hematology and Oncology	Appleton	Wisconsin	United States	54911-3496
243	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
244	Gundersen Lutheran	La Crosse	Wisconsin	United States	54601
245	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
246	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
247	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
248	Clement J. Zablocki VA Medical Center	Milwaukee	Wisconsin	United States	53295
249	Door County Cancer Center	Sturgeon Bay	Wisconsin	United States	54235-1495
250	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
251	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
252	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
253	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
254	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
255	Ottawa Health Research Institute-General Division	Ottawa	Ontario	Canada	K1H 1C4
256	Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
257	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
258	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
259	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6
260	CHUQ - Pavilion Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
261	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
262	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
263	Chinese University of Hong Kong-Prince of Wales Hospital	Shatin	Hong Kong	China	OX1 3UJ
264	King Faisal Specialist Hospital and Research Centre	Riyadh		Saudi Arabia	11211