Testing What Happens When an Immunotherapy Drug (Pembrolizumab) is Added to Radiation or Given by Itself Compared to the Usual Treatment of Chemotherapy With Radiation After Surgery for Recurrent Head and Neck Squamous Cell Carcinoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT04671667

Collaborator

(none)

282

Enrollment

108

Locations

Arms

61.7

Anticipated Duration (Months)

2.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies the effect of pembrolizumab in combination with radiation therapy or pembrolizumab alone compared to the usual approach (chemotherapy plus radiation therapy) after surgery in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or patients with a second head and neck cancer that is not from metastasis (primary). Radiation therapy uses high energy radiation or protons to kill tumor cells and shrink tumors. Chemotherapy drugs, such as cisplatin and carboplatin kill tumor cells by stopping them from dividing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab in combination with radiation therapy or pembrolizumab alone after surgery may work better than the usual approach in shrinking recurrent or primary head and neck squamous cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Head and Neck Squamous Cell Carcinoma Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Oral Cavity Squamous Cell Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma	Drug: Carboplatin Drug: Cisplatin Radiation: Intensity-Modulated Radiation Therapy Biological: Pembrolizumab Radiation: Proton Beam Radiation Therapy	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

To evaluate overall survival (OS) of adjuvant reirradiation plus concurrent pembrolizumab followed by pembrolizumab to complete 12 months total of pembrolizumab to adjuvant reirradiation plus concurrent platinum chemotherapy in high risk head and neck squamous cell carcinoma (HNSCC) patients.
To evaluate OS of adjuvant pembrolizumab for 12 months compared to adjuvant reirradiation plus concurrent platinum chemotherapy in high risk HNSCC patients.

SECONDARY OBJECTIVES:

To evaluate the following endpoints in all arms: disease free survival (DFS), locoregional control, rates of distant metastasis, toxicity.
To evaluate whether high PD-L1 expression (defined as Combined Positive Score [CPS] >=

is predictive of increased efficacy in the experimental groups compared to control.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo intensity modulated radiation therapy (IMRT) or proton beam radiation therapy (PBRT) once daily (QD) for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 6 months for up to 5 years from the date of registration

Study Design

Study Type:

Interventional

Anticipated Enrollment :

282 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized Trial of Adjuvant Therapy With Pembrolizumab After Resection of Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma With High Risk Features

Actual Study Start Date :

Jan 8, 2021

Anticipated Primary Completion Date :

Feb 28, 2026

Anticipated Study Completion Date :

Feb 28, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (pembrolizumab, IMRT, PBRT) Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.	Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Biological: Pembrolizumab Given IV Other Names: Keytruda Lambrolizumab MK-3475 SCH 900475 Radiation: Proton Beam Radiation Therapy Undergo PBRT Other Names: PBRT Proton Proton EBRT Proton External Beam Radiotherapy Proton Radiation Therapy Radiation, Proton Beam
Active Comparator: Arm B (cisplatin, carboplatin, IMRT, PBRT) Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin Given IV Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Cisplatin Given IV Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Radiation: Proton Beam Radiation Therapy Undergo PBRT Other Names: PBRT Proton Proton EBRT Proton External Beam Radiotherapy Proton Radiation Therapy Radiation, Proton Beam
Experimental: Arm C (pembrolizumab) Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.	Biological: Pembrolizumab Given IV Other Names: Keytruda Lambrolizumab MK-3475 SCH 900475

Arm

Intervention/Treatment

Experimental: Arm A (pembrolizumab, IMRT, PBRT)

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

Radiation: Intensity-Modulated Radiation Therapy

Undergo IMRT

Other Names:

IMRT

Intensity Modulated RT

Intensity-Modulated Radiotherapy

Radiation, Intensity-Modulated Radiotherapy

Biological: Pembrolizumab

Given IV

Other Names:

Keytruda

Lambrolizumab

MK-3475

SCH 900475

Radiation: Proton Beam Radiation Therapy

Undergo PBRT

Other Names:

PBRT

Proton

Proton EBRT

Proton External Beam Radiotherapy

Proton Radiation Therapy

Radiation, Proton Beam

Active Comparator: Arm B (cisplatin, carboplatin, IMRT, PBRT)

Patients receive cisplatin or carboplatin IV on day 1. Treatment repeats every 7 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo IMRT or PBRT QD for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin

Given IV

Other Names:

Blastocarb

Carboplat

Carboplatin Hexal

Carboplatino

Carboplatinum

Carbosin

Carbosol

Carbotec

CBDCA

Displata

Ercar

JM-8

Nealorin

Novoplatinum

Paraplatin

Paraplatin AQ

Paraplatine

Platinwas

Ribocarbo

Drug: Cisplatin

Given IV

Other Names:

Abiplatin

Blastolem

Briplatin

CDDP

Cis-diammine-dichloroplatinum

Cis-diamminedichloridoplatinum

Cis-diamminedichloro Platinum (II)

Cis-diamminedichloroplatinum

Cis-dichloroammine Platinum (II)

Cis-platinous Diamine Dichloride

Cis-platinum

Cis-platinum II

Cis-platinum II Diamine Dichloride

Cismaplat

Cisplatina

Cisplatinum

Cisplatyl

Citoplatino

Citosin

Cysplatyna

DDP

Lederplatin

Metaplatin

Neoplatin

Peyrone's Chloride

Peyrone's Salt

Placis

Plastistil

Platamine

Platiblastin

Platiblastin-S

Platinex

Platinol

Platinol- AQ

Platinol-AQ

Platinol-AQ VHA Plus

Platinoxan

Platinum

Platinum Diamminodichloride

Platiran

Platistin

Platosin

Radiation: Intensity-Modulated Radiation Therapy

Undergo IMRT

Other Names:

IMRT

Intensity Modulated RT

Intensity-Modulated Radiotherapy

Radiation, Intensity-Modulated Radiotherapy

Radiation: Proton Beam Radiation Therapy

Undergo PBRT

Other Names:

PBRT

Proton

Proton EBRT

Proton External Beam Radiotherapy

Proton Radiation Therapy

Radiation, Proton Beam

Experimental: Arm C (pembrolizumab)

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab

Given IV

Other Names:

Keytruda

Lambrolizumab

MK-3475

SCH 900475

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [From randomization to date of death from any cause, measured at 2 years]
Kaplan-Meier estimates will be used to estimate the OS distributions. A log-rank test with one-sided 5% type I error will be used for each of the two primary comparisons.
Incidence of adverse events [Up to 5 years from date of registration]
Assessed using Common Terminology Criteria for Adverse Events. An 80% confidence interval around the hazard ratio of the two experimental arms will be calculated. Toxicity will be compared between the two treatment arms. Toxicity will be examined by arm and compared using the Fisher's exact test.

Secondary Outcome Measures

Disease free survival [From the date of randomization to the date of recurrence, second primary tumor from the head and neck region, or death, assessed up to 5 years from date of registration]
PD-L1 expression [Up to 5 years from date of registration]
Defined as Combined Positive Score >= 20 as a predictive marker of efficacy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must be between 18 and 79 years of age
Patient must have locoregionally recurrent or second primary HNSCC (oral cavity, oropharynx, larynx, hypopharynx) in a previously radiated field
Patient must have undergone surgery with gross total resection and must be randomized within 8 weeks of surgery
Patients must have high risk disease defined as:
Positive margins and/or extra nodal extension (ENE)
Positive margins are defined as malignancy at or within 1 mm of the margin. High grade dysplasia (i.e. carcinoma in situ) at the margin is also considered positive
ENE may be either gross or microscopic
Patient must have a PD-L1 Combined Positive Score (CPS) >= 1 in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. Testing can be done locally as long as it is done in a CLIA certified laboratory. This testing must be on the tumor specimen from the resection of the patient's recurrent or second primary HNSCC
Patient must have had prior radiation to the area of recurrent or second primary tumor. This is defined as > 50% of the presurgical tumor volume having previously received a dose of > 45 Gy as determined by the treating radiation oncologist
Patient must have completed prior radiation a minimum of 6 months prior to randomization
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
Patient must not expect to conceive or father children by using by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on study treatment, and continue for 120 days after the last dose of study treatment
Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to protocol randomization)
Platelets >= 100,000/mcL (obtained =< 28 days prior to protocol randomization)
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained =< 28 days prior to protocol randomization)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 28 days prior to protocol randomization)
Creatinine clearance > 30 ml/min using the Cockcroft-Gault formula (obtained =< 28 days prior to protocol randomization)
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. Patients with New York Heart Association class III or IV heart failure are not eligible
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial as long as they have not been HIV-infected with a history of Kaposi sarcoma and/or multicentric Castleman disease

Exclusion Criteria:

Patient must not have any evidence of distant disease based on baseline imaging done within 28 days prior to randomization
Patient must not have received anti-PD-1/PD-L1 therapy for recurrent disease. If the patient received anti-PD-1/PD-L1 therapy as part of initial upfront curative intent treatment (either as part of definitive non-surgical therapy or in the adjuvant setting) in the past, the last dosage of anti-PD-1/PD-L1 therapy must have been given greater than one year prior to randomization
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab or chemotherapy if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patient must not have a current active infection that requires systemic treatment at time of randomization
Patient must not have a history of non-infectious pneumonitis requiring steroids within 3 years prior to randomization
Patient must not have a history of solid organ transplant or stem cell transplant
Patient must not be on immunosuppressive medication within 7 days prior to randomization, EXCEPT for the following: a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c) steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
Patient must not have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
Patient must not have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Patient must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
NOTE: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
4	Sutter Roseville Medical Center	Roseville	California	United States	95661
5	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut	United States	06510
6	Yale University	New Haven	Connecticut	United States	06520
7	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut	United States	06611
8	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut	United States	06385
9	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida	United States	33146
10	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida	United States	33442
11	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
12	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
13	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida	United States	33324
14	Moffitt Cancer Center-International Plaza	Tampa	Florida	United States	33607
15	Moffitt Cancer Center - McKinley Campus	Tampa	Florida	United States	33612
16	Moffitt Cancer Center	Tampa	Florida	United States	33612
17	Emory Proton Therapy Center	Atlanta	Georgia	United States	30308
18	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
19	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	United States	30322
20	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
21	Carle on Vermilion	Danville	Illinois	United States	61832
22	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
23	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
24	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
25	Crossroads Cancer Center	Effingham	Illinois	United States	62401
26	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
27	Loyola University Medical Center	Maywood	Illinois	United States	60153
28	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
29	Springfield Clinic	Springfield	Illinois	United States	62702
30	Memorial Medical Center	Springfield	Illinois	United States	62781
31	Carle Cancer Center	Urbana	Illinois	United States	61801
32	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
33	Reid Health	Richmond	Indiana	United States	47374
34	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
35	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
36	Broadlawns Medical Center	Des Moines	Iowa	United States	50314
37	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
38	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
39	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
40	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
41	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas	United States	66211
42	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas	United States	66205
43	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
44	Maryland Proton Treatment Center	Baltimore	Maryland	United States	21201
45	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
46	Central Maryland Radiation Oncology in Howard County	Columbia	Maryland	United States	21044
47	UM Baltimore Washington Medical Center/Tate Cancer Center	Glen Burnie	Maryland	United States	21061
48	Tufts Medical Center	Boston	Massachusetts	United States	02111
49	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
50	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
51	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
52	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
53	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
54	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
55	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri	United States	63141
56	University of Kansas Cancer Center - North	Kansas City	Missouri	United States	64154
57	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri	United States	64064
58	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri	United States	64116
59	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
60	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
61	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri	United States	63136
62	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri	United States	63376
63	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
64	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
65	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
66	Mount Sinai Union Square	New York	New York	United States	10003
67	Mount Sinai Chelsea	New York	New York	United States	10011
68	Mount Sinai Hospital	New York	New York	United States	10029
69	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
70	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
71	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
72	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
73	Miami Valley Hospital South	Centerville	Ohio	United States	45459
74	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
75	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio	United States	45415
76	Miami Valley Hospital North	Dayton	Ohio	United States	45415
77	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
78	Kettering Medical Center	Kettering	Ohio	United States	45429
79	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
80	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
81	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
82	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
83	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
84	Providence Portland Medical Center	Portland	Oregon	United States	97213
85	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
86	UPMC Altoona	Altoona	Pennsylvania	United States	16601
87	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
88	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
89	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
90	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
91	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
92	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
93	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
94	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
95	UPMC Memorial	York	Pennsylvania	United States	17408
96	Medical University of South Carolina	Charleston	South Carolina	United States	29425
97	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
98	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
99	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
100	VCU Massey Cancer Center at Stony Point	Richmond	Virginia	United States	23235
101	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
102	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
103	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
104	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
105	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin	United States	53051
106	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
107	Drexel Town Square Health Center	Oak Creek	Wisconsin	United States	53154
108	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495