MedPath

Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Limited Stage or Extensive Stage Small Cell Lung Cancer

Phase 2
Active, not recruiting
Conditions
Limited Stage Small Cell Lung Carcinoma
Extensive Stage Small Cell Lung Carcinoma
Interventions
Radiation: Intensity-Modulated Radiation Therapy
Radiation: Three-Dimensional Conformal Radiation Therapy
Registration Number
NCT02635009
Lead Sponsor
NRG Oncology
Brief Summary

This randomized phase II/III trial studies how well whole-brain radiation therapy works and compares it with or without hippocampal avoidance in treating patients with small cell lung cancer that is found in one lung, the tissues between the lungs, and nearby lymph nodes only (limited stage) or has spread outside of the lung in which it began or to other parts of the body (extensive stage). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The hippocampus is part of the brain that is important for memory. Avoiding the hippocampus during whole-brain radiation could decrease the chance of side effects on memory and thinking. It is not yet known whether giving whole-brain radiation therapy is more effective with or without hippocampal avoidance in treating patients with small cell lung cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine whether the 12-month intracranial relapse rate following hippocampal avoidance (HA)-prophylactic cranial irradiation (PCI) is non-inferior compared to the rate following PCI for patients with small cell lung cancer (SCLC). (Randomized Phase II Component \[Non-Inferiority\]) II. Determine whether HA-PCI reduces the likelihood of 6-month deterioration from baseline in Hopkins Verbal Learning Test (HVLT)-Revised (R) delayed recall compared to PCI for patients with SCLC. (Phase III Component \[Efficacy\])

SECONDARY OBJECTIVES:

I. Compare time to cognitive failure, as measured by a battery of tests (HVLT-R, Controlled Oral Word Association (COWA) test, and Trail Making Test (TMT) parts A and B), after PCI versus HA-PCI in SCLC.

II. Compare time to cognitive failure as separately measured by each test (HVLT-R for Total Recall and Delayed Recognition, COWA test, and TMT parts A and B), after PCI versus HA-PCI for SCLC.

III. Compare patient-reported cognitive functioning and other quality of life domains (assessed by the European Organization for Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire (QLQ)-Core \[C\]30 and BN20) between PCI versus HA-PCI for patients with SCLC.

IV. Compare overall survival after PCI versus HA-PCI for patients with SCLC.

V. Compare 12-month intracranial relapse rate (at completion of phase III) and time to intracranial relapse after PCI versus HA-PCI for patients with SCLC.

VI. Evaluate adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria.

VII. Correlate changes in health-related quality of life (HRQOL) domains with changes in cognitive testing outcomes following PCI versus HA-PCI for patients with SCLC.

VIII. Assess cost-effectiveness of HA-PCI (intensity modulated radiation therapy \[IMRT\]) and PCI (3-dimensional conformal radiation therapy \[3DCRT\]) using the EuroQual (EQ)-5-Dimensions (5D)-5L.

IX. Correlate miRNA signatures with cognitive failure in SCLC patients who received PCI and HA-PCI.

X. Evaluate Apolipoprotein E (APOE) genotyping as potential predictor of neurocognitive decline, hippocampal atrophy after brain irradiation and/or differential benefit from hippocampal avoidance.

XI. Evaluate baseline MR imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.

TERTIARY OBJECTIVES:

I. Collect serum, whole blood, and urine for future translational research analyses.

II. Evaluate baseline magnetic resonance (MR) imaging biomarkers of white matter injury and hippocampal volumetry as potential predictors of cognitive decline and differential benefit from HA-PCI as compared to PCI.

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

ARM I: Patients undergo PCI using 3DCRT daily for 2 weeks.

ARM II: Patients undergo PCI with HA using IMRT daily for 2 weeks.

After completion of study treatment, patients are followed every 3 months for 1 year, then every 6 months until 3 years and then annually until death.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
418
Inclusion Criteria

Not provided

Exclusion Criteria
  • Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields

  • Radiographic evidence of central nervous system (CNS) metastases

  • Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt

  • Planned concurrent chemotherapy during PCI

    • Concurrent atezolizumab permitted
  • Concomitant invasive malignancy or invasive malignancy within the past five years other than non-melanomatous skin cancer; history of in situ carcinoma (e.g. ductal carcinoma in situ of breast, in situ carcinoma of the cervix, vulva or larynx) is permitted

  • Contraindication to MR imaging, such as implanted metal devices or foreign bodies or severe claustrophobia

  • Severe, active comorbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months

    • Transmural myocardial infarction within the last 6 months

    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

    • Uncontrolled, clinically significant cardiac arrhythmias

    • HIV positive with CD4 count < 200 cells/microliter;

      1. Note: Patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to Step 1 registration.
      2. Note: HIV testing is not required for eligibility for this protocol.
  • Pregnant or lactating women or women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PCI with HA using IMRTIntensity-Modulated Radiation TherapyPCI with hippocampal avoidance (HA) using intensity-modulated radiation therapy (IMRT) for 2 weeks, 5 fractions/week.
PCI using 3DCRTThree-Dimensional Conformal Radiation TherapyProphylactic cranial irradiation (PCI) using three-dimensional conformal radiation therapy (3DCRT) for 2 weeks, 5 fractions/week.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)Baseline and six months

The HVLT-R delayed recall test assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials to recall after a 20-minute delay. The score is the sum of the number of words correctly recalled and ranges from 0 to 36, with a higher score indicating better functioning. Deterioration is defined a decrease from baseline of at least 3 points.

Number of Participants With Intracranial Relapse at 12 Months (Phase II)From baseline to 12 months

Intracranial relapse, defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)Baseline, 18, 24 months.

The HVLT-R Delayed Recall test assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials, this test requires recalling the 12 targets after a 20-minute delay. Raw scores are sum of the number of targets correctly recalled. The score ranges from 0 to 12. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 3 points.

Number of Participants With Deterioration in TMT Part B Score (Phase III)Baseline, 18, 24 months.

The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the second part (Part B, reported here), the subject alternates between numbers and letters (1, A, 2, B, etc.). The score is the amount of time, in seconds, that it takes the patient to complete the maze. The score range for Part B is 0 to 300 (5 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 26 seconds.

If reporting a score on a scale, please include the unabbreviated scale title, the minimum and maximum values, and whether higher scores mean a better or worse outcome.

Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)Baseline, 18, 24 months.

The TMT is a neuropsychological test of visual attention and task switching that can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning. Subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first (Part A, reported here), the targets are all numbers (1, 2, 3, etc.) and the test taker needs to connect them in sequential order. The score is the amount of time, in seconds, that it takes the patient to complete the maze. The range for Part A is 0 to 180 (3 minutes). Lower scores indicate better functioning. Deterioration is defined an increase from baseline of at least 12 seconds.

Number of Participants With Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) Global Health Status (Phase III)Baseline, 3, 6, 12 months.

The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)Baseline,18, 24 months.

he HVLT-R Total Recall score assesses verbal learning and memory. The test involves memorizing a list of 12 nouns for 3 consecutive trials. Raw score is the sum of the number of targets correctly recalled, ranging from 0 to 36. Higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 5 points.

Number of Participants by Highest Grade Adverse Event Reported (Phase III)From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.

Common Terminology Criteria for Adverse Events (version 5) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.

Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)Baseline to two years

The incremental cost per quality-adjusted life year (QALY) ratio will be calculated as total cost of the PCI with HA using IMRT arm (Arm 2) minus total cost of the PCI using 3DCRT arm (Arm 1), divided by the quality adjusted survival of the Arm 1 patients minus the quality adjusted survival of Arm 2 patients.

Percentage of Participants With Neurocognitive Failure (Phase III)Randomization to date of failure, death, or last known follow-up whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.

Neurocognitive failure is defined as the first instance of neurocognitive decline in any of six assessments, as determined my reliable change index: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test (TMT) part A, TMT part B, and Controlled Oral Word Association (COWA). Failure time is defined as time from randomization to failure, death (competing event), or last follow-up (censored). Neurocognitive failure rates are estimated using the cumulative incidence method. The distributions of failure times are compared, which is reported in the statistical analysis results. Six-month rates are reported here. Analysis occurred after all patients had been on study for at least six months.

Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)Baseline, 18, 24 months.

The HVLT-R Delayed Recognition assesses verbal learning and memory. After memorizing a list of 12 nouns for 3 consecutive trials and recalling the 12 targets after a 20-minute delay, the test involves then identifying the 12 targets from a list of semantically related or unrelated items (delayed recognition). Raw scores are the sum of targets incorrectly identified subtracted from the sum of the number of targets correctly identified. The score ranges from -12 to 12 for recognition. A higher score indicates better functioning. Deterioration is defined a decrease from baseline of at least 2 points.

Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.

Intracranial Relapse Rate (Phase III)From date of randomization to date of intracranial relapse, death, or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 7.2 years.

Intracranial relapse is defined as the development of a new brain metastasis as documented on brain MRI with contrast or head CT with contrast. Time to intracranial relapse is defined as time from randomization to the date of first intracranial relapse, last known follow-up (censored), or death without intracranial relapse (competing risk), whichever occurred first. Intracranial relapse rates are estimated using the cumulative incidence method. The distributions of intracranial relapse times are compared between the arms, which is reported in the statistical analysis results. One-year rates are provided here. Analysis occurred at time of the phase III primary analysis.

White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III)Baseline to 6 months

Pearson correlation coefficients will be used to assess the effect of hippocampal volume and FLAIR volume change on baseline neurocognitive function, as measured by the HVLT-R, COWA, and TMT, separately for each arm.

Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)Baseline,18, 24 months.

The COWA is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter. Patients are given 1 minute to name as many words as possible beginning with the designated letter. The procedure is then repeated for the remaining two letters. Two alternate forms of the COWA are employed to minimize practice effects. The score is the sum of the correct responses with a range of 0 to infinity. A higher score indicates better functioning. Deterioration is defined an increase from baseline of at least 12 words.

Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)Baseline,18, 24 months.

The QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life (QOL) of cancer patients participating in international clinical trials. Global Health Status is considered a measure of overall quality of life and is calculated from two questions whose raw scores are averaged and then transformed to a range of 0 (worst) to 100 (best). Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)Baseline, 3, 6, 12 months.

The EORTC QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.

Overall Survival (Phase III)From the date of randomization to the date of death or last follow-up. Maximum follow-up time at time of analysis was 7.2 years.

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 8 months.

Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)Baseline,18, 24 months.

The EORTC QLQ-C30 is a 30-item self-report questionnaire used to assess the health-related quality of life of cancer patients participating in international clinical trials. A functional scale raw score is transformed to a range of 0 (worst) to 100 (best) in which a high score represents a healthy level of functioning. Deterioration is defined a reduction of 10% from baseline.

Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)Baseline,18, 24 months.

The QLQ-BN20 is a 20-item self-report questionnaire supplement to the QLQ-C30 for patients used to assess the health-related quality of life of brain cancer patients. A symptom scale raw score is transformed to a range of 0 (best) to 100 (worst) in which a high score represents a high level of symptomatology/problems. For patients with a baseline score of 0, a follow-up score of ≥ 10 is considered as a deterioration. Otherwise, a 10% increase is considered as a deterioration.

Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months6 months

The Pearson correlation coefficient was calculated for EORTC QLQ-C30 (physical, role, emotional, cognitive, and social functioning domains and global health status) and QLQ-BN20 (motor dysfunction and communication deficit) versus the standardized neurocognitive function (HVLT-R total recall, HVLT-R delayed recall, HVLT-R delayed recognition, COWA, TMT parts A and B) and the Clinical Trial Battery Composite (CTB Comp) score (mean of the z-scores for the six NCF scores) for all patients, treatment arms combined. The Pearson correlation coefficient is computed for each pair of measurements, resulting in 48 correlation coefficients. Possible values range from -1 (negatively correlated) to 1(positively correlated), with 0 indicating no correlation. A correlation with a value in range -0.35 to 0.35 is considered weak and is indicated by "0" in the table. Because of the large number of comparisons, only individual correlation coefficients outside that range are listed here.

Trial Locations

Locations (285)

Vince Lombardi Cancer Clinic - Oshkosh

🇺🇸

Oshkosh, Wisconsin, United States

Aspirus Regional Cancer Center

🇺🇸

Wausau, Wisconsin, United States

Diagnostic and Treatment Center

🇺🇸

Weston, Wisconsin, United States

Allan Blair Cancer Centre

🇨🇦

Regina, Saskatchewan, Canada

Grady Health System

🇺🇸

Atlanta, Georgia, United States

Northside Hospital

🇺🇸

Atlanta, Georgia, United States

University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

🇺🇸

Baltimore, Maryland, United States

Temple University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Emory University Hospital/Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

The Cancer Center of Hawaii-Pali Momi

🇺🇸

'Aiea, Hawaii, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Saint Joseph Hospital - Orange

🇺🇸

Orange, California, United States

Saint Alphonsus Cancer Care Center-Nampa

🇺🇸

Nampa, Idaho, United States

John H Stroger Jr Hospital of Cook County

🇺🇸

Chicago, Illinois, United States

Crossroads Cancer Center

🇺🇸

Effingham, Illinois, United States

Northwestern Medicine Cancer Center Delnor

🇺🇸

Geneva, Illinois, United States

Condell Memorial Hospital

🇺🇸

Libertyville, Illinois, United States

Memorial Medical Center

🇺🇸

Springfield, Illinois, United States

Goshen Center for Cancer Care

🇺🇸

Goshen, Indiana, United States

Parkview Regional Medical Center

🇺🇸

Fort Wayne, Indiana, United States

IU Health Ball Memorial Hospital

🇺🇸

Muncie, Indiana, United States

UM Upper Chesapeake Medical Center

🇺🇸

Bel Air, Maryland, United States

Lawrence Memorial Hospital

🇺🇸

Lawrence, Kansas, United States

UM Saint Joseph Medical Center

🇺🇸

Towson, Maryland, United States

McLaren Cancer Institute-Clarkston

🇺🇸

Clarkston, Michigan, United States

Miami Cancer Institute

🇺🇸

Miami, Florida, United States

MedStar Good Samaritan Hospital

🇺🇸

Baltimore, Maryland, United States

Marin General Hospital

🇺🇸

Greenbrae, California, United States

Saint Luke's Cancer Institute - Nampa

🇺🇸

Nampa, Idaho, United States

OSF Saint Francis Medical Center

🇺🇸

Peoria, Illinois, United States

Saint Alphonsus Cancer Care Center-Boise

🇺🇸

Boise, Idaho, United States

Edward Hines Jr VA Hospital

🇺🇸

Hines, Illinois, United States

Michigan Healthcare Professionals Farmington

🇺🇸

Farmington Hills, Michigan, United States

Michigan Healthcare Professionals Macomb

🇺🇸

Macomb, Michigan, United States

Genesys Hurley Cancer Institute

🇺🇸

Flint, Michigan, United States

Mayo Clinic Health System in Albert Lea

🇺🇸

Albert Lea, Minnesota, United States

Beaumont Hospital - Dearborn

🇺🇸

Dearborn, Michigan, United States

McLaren Cancer Institute-Central Michigan

🇺🇸

Mount Pleasant, Michigan, United States

McLaren Cancer Institute-Flint

🇺🇸

Flint, Michigan, United States

Benefis Healthcare- Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Billings Clinic Cancer Center

🇺🇸

Billings, Montana, United States

Henry Ford Macomb Hospital-Clinton Township

🇺🇸

Clinton Township, Michigan, United States

McLaren Cancer Institute-Lapeer Region

🇺🇸

Lapeer, Michigan, United States

Mercy Hospital Saint Louis

🇺🇸

Saint Louis, Missouri, United States

Freeman Health System

🇺🇸

Joplin, Missouri, United States

Mayo Clinic Radiation Therapy-Northfield

🇺🇸

Northfield, Minnesota, United States

William Beaumont Hospital - Troy

🇺🇸

Troy, Michigan, United States

McLaren Cancer Institute-Owosso

🇺🇸

Owosso, Michigan, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Saint Luke's Hospital of Duluth

🇺🇸

Duluth, Minnesota, United States

Community Medical Hospital

🇺🇸

Missoula, Montana, United States

University of Kansas Cancer Center at North Kansas City Hospital

🇺🇸

North Kansas City, Missouri, United States

Henry Ford West Bloomfield Hospital

🇺🇸

West Bloomfield, Michigan, United States

Mayo Clinic Health Systems-Mankato

🇺🇸

Mankato, Minnesota, United States

Spectrum Health at Butterworth Campus

🇺🇸

Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital

🇺🇸

Grand Rapids, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital

🇺🇸

Livonia, Michigan, United States

Michigan Healthcare Professionals Clarkston

🇺🇸

Clarkston, Michigan, United States

Siteman Cancer Center-South County

🇺🇸

Saint Louis, Missouri, United States

Missouri Baptist Medical Center

🇺🇸

Saint Louis, Missouri, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

🇺🇸

Lebanon, New Hampshire, United States

University of Rochester

🇺🇸

Rochester, New York, United States

Memorial Sloan Kettering Bergen

🇺🇸

Montvale, New Jersey, United States

Carolinas Medical Center/Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Lenox Hill Hospital

🇺🇸

New York, New York, United States

Saint Francis Medical Center

🇺🇸

Cape Girardeau, Missouri, United States

Renown Regional Medical Center

🇺🇸

Reno, Nevada, United States

Memorial Sloan Kettering Nassau

🇺🇸

Uniondale, New York, United States

Englewood Hospital and Medical Center

🇺🇸

Englewood, New Jersey, United States

State University of New York Upstate Medical University

🇺🇸

Syracuse, New York, United States

Memorial Sloan Kettering Monmouth

🇺🇸

Middletown, New Jersey, United States

Memorial Sloan Kettering Basking Ridge

🇺🇸

Basking Ridge, New Jersey, United States

Virtua Voorhees

🇺🇸

Voorhees, New Jersey, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Mount Carmel Health Center West

🇺🇸

Columbus, Ohio, United States

Atrium Health University City/LCI-University

🇺🇸

Charlotte, North Carolina, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Atrium Health Cabarrus/LCI-Concord

🇺🇸

Concord, North Carolina, United States

University Hospitals Parma Medical Center

🇺🇸

Parma, Ohio, United States

Adena Regional Medical Center

🇺🇸

Chillicothe, Ohio, United States

Geisinger Medical Oncology-Lewisburg

🇺🇸

Lewisburg, Pennsylvania, United States

Sanford Bismarck Medical Center

🇺🇸

Bismarck, North Dakota, United States

WellSpan Health-York Cancer Center

🇺🇸

York, Pennsylvania, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

🇺🇸

New York, New York, United States

Atrium Health Pineville/LCI-Pineville

🇺🇸

Charlotte, North Carolina, United States

Virtua Memorial

🇺🇸

Mount Holly, New Jersey, United States

Prisma Health Cancer Institute - Faris

🇺🇸

Greenville, South Carolina, United States

Christiana Care Health System-Concord Health Center

🇺🇸

Chadds Ford, Pennsylvania, United States

Geauga Hospital

🇺🇸

Chardon, Ohio, United States

Cleveland Clinic Wooster Family Health and Surgery Center

🇺🇸

Wooster, Ohio, United States

Crozer-Keystone Regional Cancer Center at Broomall

🇺🇸

Broomall, Pennsylvania, United States

Penn State Health Saint Joseph Medical Center

🇺🇸

Reading, Pennsylvania, United States

Geisinger Medical Center

🇺🇸

Danville, Pennsylvania, United States

Case Western Reserve University

🇺🇸

Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

Atrium Health Union/LCI-Union

🇺🇸

Monroe, North Carolina, United States

Mercy Cancer Center-Elyria

🇺🇸

Elyria, Ohio, United States

UH Seidman Cancer Center at Southwest General Hospital

🇺🇸

Middleburg Heights, Ohio, United States

Legacy Mount Hood Medical Center

🇺🇸

Gresham, Oregon, United States

Adams Cancer Center

🇺🇸

Gettysburg, Pennsylvania, United States

Crozer Regional Cancer Center at Brinton Lake

🇺🇸

Glen Mills, Pennsylvania, United States

Jefferson Abington Hospital

🇺🇸

Abington, Pennsylvania, United States

Prisma Health Cancer Institute - Eastside

🇺🇸

Greenville, South Carolina, United States

Summa Health System - Akron Campus

🇺🇸

Akron, Ohio, United States

Northwell Health Imbert Cancer Center

🇺🇸

Bay Shore, New York, United States

Blount Memorial Hospital

🇺🇸

Maryville, Tennessee, United States

Sanford Roger Maris Cancer Center

🇺🇸

Fargo, North Dakota, United States

Memorial Sloan Kettering Commack

🇺🇸

Commack, New York, United States

Memorial Sloan Kettering Westchester

🇺🇸

Harrison, New York, United States

Cleveland Clinic Cancer Center Independence

🇺🇸

Independence, Ohio, United States

AnMed Health Cancer Center

🇺🇸

Anderson, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

🇺🇸

Sioux Falls, South Dakota, United States

Atrium Health Cleveland/LCI-Cleveland

🇺🇸

Shelby, North Carolina, United States

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

Cleveland Clinic Cancer Center/Fairview Hospital

🇺🇸

Cleveland, Ohio, United States

Riddle Memorial Hospital

🇺🇸

Media, Pennsylvania, United States

Ascension Southeast Wisconsin Hospital - Elmbrook Campus

🇺🇸

Brookfield, Wisconsin, United States

Cleveland Clinic Akron General

🇺🇸

Akron, Ohio, United States

Dayton Physician LLC-Miami Valley Hospital North

🇺🇸

Dayton, Ohio, United States

University of Vermont Medical Center

🇺🇸

Burlington, Vermont, United States

Bryn Mawr Hospital

🇺🇸

Bryn Mawr, Pennsylvania, United States

Northeast Radiation Oncology Center

🇺🇸

Dunmore, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center

🇺🇸

Wilkes-Barre, Pennsylvania, United States

Aurora Cancer Care-Kenosha South

🇺🇸

Kenosha, Wisconsin, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

Aurora West Allis Medical Center

🇺🇸

West Allis, Wisconsin, United States

Prisma Health Cancer Institute - Spartanburg

🇺🇸

Boiling Springs, South Carolina, United States

Rock Hill Radiation Therapy Center

🇺🇸

Rock Hill, South Carolina, United States

Mayo Clinic Health System-Franciscan Healthcare

🇺🇸

La Crosse, Wisconsin, United States

Reading Hospital

🇺🇸

West Reading, Pennsylvania, United States

UTMB Cancer Center at Victory Lakes

🇺🇸

League City, Texas, United States

Froedtert Menomonee Falls Hospital

🇺🇸

Menomonee Falls, Wisconsin, United States

Ascension All Saints Hospital

🇺🇸

Racine, Wisconsin, United States

Lankenau Medical Center

🇺🇸

Wynnewood, Pennsylvania, United States

Central Vermont Medical Center/National Life Cancer Treatment

🇺🇸

Berlin, Vermont, United States

Gundersen Lutheran Medical Center

🇺🇸

La Crosse, Wisconsin, United States

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Ottawa Hospital and Cancer Center-General Campus

🇨🇦

Ottawa, Ontario, Canada

Thompson Cancer Survival Center

🇺🇸

Knoxville, Tennessee, United States

Mayo Clinic Health System-Eau Claire Clinic

🇺🇸

Eau Claire, Wisconsin, United States

Self Regional Healthcare

🇺🇸

Greenwood, South Carolina, United States

Norris Cotton Cancer Center-North

🇺🇸

Saint Johnsbury, Vermont, United States

Langlade Hospital and Cancer Center

🇺🇸

Antigo, Wisconsin, United States

Ogden Regional Medical Center

🇺🇸

Ogden, Utah, United States

Aspirus Cancer Care - Wisconsin Rapids

🇺🇸

Wisconsin Rapids, Wisconsin, United States

CHUM - Centre Hospitalier de l'Universite de Montreal

🇨🇦

Montreal, Quebec, Canada

UW Cancer Center Johnson Creek

🇺🇸

Johnson Creek, Wisconsin, United States

Aurora Medical Center in Summit

🇺🇸

Summit, Wisconsin, United States

West Virginia University Healthcare

🇺🇸

Morgantown, West Virginia, United States

Aurora BayCare Medical Center

🇺🇸

Green Bay, Wisconsin, United States

Mayo Clinic Health System Eau Claire Hospital-Luther Campus

🇺🇸

Eau Claire, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point

🇺🇸

Stevens Point, Wisconsin, United States

Wheeling Hospital/Schiffler Cancer Center

🇺🇸

Wheeling, West Virginia, United States

Aurora Cancer Care-Grafton

🇺🇸

Grafton, Wisconsin, United States

Kingston Health Sciences Centre

🇨🇦

Kingston, Ontario, Canada

Vince Lombardi Cancer Clinic-Two Rivers

🇺🇸

Two Rivers, Wisconsin, United States

Marshfield Medical Center - Weston

🇺🇸

Weston, Wisconsin, United States

McGill University Department of Oncology

🇨🇦

Montreal, Quebec, Canada

University Health Network-Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Saskatoon Cancer Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

CHUM - Hopital Notre-Dame

🇨🇦

Montreal, Quebec, Canada

CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)

🇨🇦

Quebec City, Quebec, Canada

Abbott-Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

Queen's Medical Center

🇺🇸

Honolulu, Hawaii, United States

The Cancer Center of Hawaii-Liliha

🇺🇸

Honolulu, Hawaii, United States

California Pacific Medical Center-Pacific Campus

🇺🇸

San Francisco, California, United States

Huntsman Cancer Institute/University of Utah

🇺🇸

Salt Lake City, Utah, United States

Vanderbilt University/Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Wayne State University/Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

University of Alabama at Birmingham Cancer Center

🇺🇸

Birmingham, Alabama, United States

Legacy Good Samaritan Hospital and Medical Center

🇺🇸

Portland, Oregon, United States

Mayo Clinic in Rochester

🇺🇸

Rochester, Minnesota, United States

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

Stronach Regional Health Centre at Southlake

🇨🇦

Newmarket, Ontario, Canada

The Research Institute of the McGill University Health Centre (MUHC)

🇨🇦

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

🇨🇦

Sherbrooke, Quebec, Canada

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Saint Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Aurora Sinai Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Siteman Cancer Center at West County Hospital

🇺🇸

Creve Coeur, Missouri, United States

Park Nicollet Clinic - Saint Louis Park

🇺🇸

Saint Louis Park, Minnesota, United States

New York-Presbyterian/Brooklyn Methodist Hospital

🇺🇸

Brooklyn, New York, United States

Arnot Ogden Medical Center/Falck Cancer Center

🇺🇸

Elmira, New York, United States

Northwell Health/Center for Advanced Medicine

🇺🇸

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Staten Island University Hospital

🇺🇸

Staten Island, New York, United States

William Beaumont Hospital-Royal Oak

🇺🇸

Royal Oak, Michigan, United States

McLaren-Port Huron

🇺🇸

Port Huron, Michigan, United States

McLaren Cancer Institute-Macomb

🇺🇸

Mount Clemens, Michigan, United States

Trinity Health Muskegon Hospital

🇺🇸

Muskegon, Michigan, United States

McLaren Cancer Institute-Northern Michigan

🇺🇸

Petoskey, Michigan, United States

Lakeland Medical Center Saint Joseph

🇺🇸

Saint Joseph, Michigan, United States

GenesisCare USA - Troy

🇺🇸

Troy, Michigan, United States

Jefferson Torresdale Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

Saint Joseph Mercy Hospital

🇺🇸

Ann Arbor, Michigan, United States

University of California Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Banner University Medical Center - Tucson

🇺🇸

Tucson, Arizona, United States

Lewis and Faye Manderson Cancer Center

🇺🇸

Tuscaloosa, Alabama, United States

Mercy UC Davis Cancer Center

🇺🇸

Merced, California, United States

Los Angeles General Medical Center

🇺🇸

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Kaiser Permanente Oakland-Broadway

🇺🇸

Oakland, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

🇺🇸

Roseville, California, United States

Kaiser Permanente-Rancho Cordova Cancer Center

🇺🇸

Rancho Cordova, California, United States

The Permanente Medical Group-Roseville Radiation Oncology

🇺🇸

Roseville, California, United States

Sutter Medical Center Sacramento

🇺🇸

Sacramento, California, United States

Kaiser Permanente Medical Center - Santa Clara

🇺🇸

Santa Clara, California, United States

Gene Upshaw Memorial Tahoe Forest Cancer Center

🇺🇸

Truckee, California, United States

Swedish Medical Center

🇺🇸

Englewood, Colorado, United States

Sutter Solano Medical Center/Cancer Center

🇺🇸

Vallejo, California, United States

Hartford HealthCare - Saint Vincent's Medical Center

🇺🇸

Bridgeport, Connecticut, United States

Poudre Valley Hospital

🇺🇸

Fort Collins, Colorado, United States

Christiana Care Health System-Christiana Hospital

🇺🇸

Newark, Delaware, United States

Boca Raton Regional Hospital

🇺🇸

Boca Raton, Florida, United States

Helen F Graham Cancer Center

🇺🇸

Newark, Delaware, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

🇺🇸

Coral Gables, Florida, United States

Broward Health Medical Center

🇺🇸

Fort Lauderdale, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

🇺🇸

Miami, Florida, United States

Emory University Hospital Midtown

🇺🇸

Atlanta, Georgia, United States

Piedmont Hospital

🇺🇸

Atlanta, Georgia, United States

Memorial Health University Medical Center

🇺🇸

Savannah, Georgia, United States

Northside Hospital-Forsyth

🇺🇸

Cumming, Georgia, United States

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

🇺🇸

Savannah, Georgia, United States

Saint Luke's Cancer Institute - Boise

🇺🇸

Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell

🇺🇸

Caldwell, Idaho, United States

Saint Luke's Cancer Institute - Meridian

🇺🇸

Meridian, Idaho, United States

Saint Luke's Cancer Institute - Twin Falls

🇺🇸

Twin Falls, Idaho, United States

Decatur Memorial Hospital

🇺🇸

Decatur, Illinois, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

Illinois CancerCare-Peoria

🇺🇸

Peoria, Illinois, United States

Methodist Medical Center of Illinois

🇺🇸

Peoria, Illinois, United States

Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

🇺🇸

Warrenville, Illinois, United States

Parkview Hospital Randallia

🇺🇸

Fort Wayne, Indiana, United States

Ascension Saint Vincent Anderson

🇺🇸

Anderson, Indiana, United States

Saint Luke's Hospital

🇺🇸

Cedar Rapids, Iowa, United States

Mercy Hospital

🇺🇸

Cedar Rapids, Iowa, United States

Wesley Medical Center

🇺🇸

Wichita, Kansas, United States

Ascension Via Christi Hospitals Wichita

🇺🇸

Wichita, Kansas, United States

University of Kansas Cancer Center-Overland Park

🇺🇸

Overland Park, Kansas, United States

University of Kansas Cancer Center

🇺🇸

Kansas City, Kansas, United States

Anne Arundel Medical Center

🇺🇸

Annapolis, Maryland, United States

University of Maryland/Greenebaum Cancer Center

🇺🇸

Baltimore, Maryland, United States

Central Maryland Radiation Oncology in Howard County

🇺🇸

Columbia, Maryland, United States

UM Baltimore Washington Medical Center/Tate Cancer Center

🇺🇸

Glen Burnie, Maryland, United States

TidalHealth Peninsula Regional

🇺🇸

Salisbury, Maryland, United States

Lahey Hospital and Medical Center

🇺🇸

Burlington, Massachusetts, United States

Lowell General Hospital

🇺🇸

Lowell, Massachusetts, United States

McLaren Cancer Institute-Bay City

🇺🇸

Bay City, Michigan, United States

Saint Joseph Mercy Brighton

🇺🇸

Brighton, Michigan, United States

Henry Ford Cancer Institute-Downriver

🇺🇸

Brownstown, Michigan, United States

Saint Joseph Mercy Chelsea

🇺🇸

Chelsea, Michigan, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

Orlando Health Cancer Institute

🇺🇸

Orlando, Florida, United States

TidalHealth Richard A Henson Cancer Institute

🇺🇸

Ocean Pines, Maryland, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

UMass Memorial Medical Center - University Campus

🇺🇸

Worcester, Massachusetts, United States

Saint Luke's Hospital of Kansas City

🇺🇸

Kansas City, Missouri, United States

North Kansas City Hospital

🇺🇸

Kansas City, Missouri, United States

University of Kansas Cancer Center - North

🇺🇸

Kansas City, Missouri, United States

Tulane University School of Medicine

🇺🇸

New Orleans, Louisiana, United States

Montefiore Medical Center-Einstein Campus

🇺🇸

Bronx, New York, United States

Montefiore Medical Center - Moses Campus

🇺🇸

Bronx, New York, United States

Virginia Commonwealth University/Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

Iowa Methodist Medical Center

🇺🇸

Des Moines, Iowa, United States

University of Kentucky/Markey Cancer Center

🇺🇸

Lexington, Kentucky, United States

University of Wisconsin Carbone Cancer Center

🇺🇸

Madison, Wisconsin, United States

Saint Joseph Mercy Oakland

🇺🇸

Pontiac, Michigan, United States

UH Seidman Cancer Center at Lake Health Mentor Campus

🇺🇸

Mentor, Ohio, United States

UHHS-Westlake Medical Center

🇺🇸

Westlake, Ohio, United States

Cleveland Clinic Cancer Center Strongsville

🇺🇸

Strongsville, Ohio, United States

The Radiation Oncology Center-Hilton Head/Bluffton

🇺🇸

Hilton Head Island, South Carolina, United States

Lancaster Radiation Therapy Center

🇺🇸

Lancaster, South Carolina, United States

Wentworth-Douglass Hospital

🇺🇸

Dover, New Hampshire, United States

Ascension Saint Francis - Reiman Cancer Center

🇺🇸

Franklin, Wisconsin, United States

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