Clinical trial NCT02635009: Whole-Brain Radiation Therapy With or Without Hippocampal Avoidance in Limited Stage or Extensive Stage Small Cell Lung Cancer
Official title: Randomized Phase II/III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Extensive Stage Small Cell Lung Carcinoma
Limited Stage Small Cell Lung Carcinoma
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Radiation Therapy Oncology Group
First posted: 2015-12-18
Enrollment: 418
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: Inclusion Criteria \[prior to Step 1 registration\]:

* Histologic proof or unequivocal cytologic proof (fine needle aspiration, biopsy or two positive sputa) of SCLC within 250 days prior to Step 1 registration

  * High-grade neuroendocrine carcinoma or combined SCLC and NSCLC is permitted.
* Patients must have received chemotherapy and be registered to Step 1 registration no earlier than 7 days and no later than 56 days after completing chemotherapy. Note:

  * Post-chemotherapy restaging imaging must be completed no more than 56 days prior to Step 1 registration.
  * For patients with extensive-stage small cell lung cancer who are being considered for consolidative thoracic radiotherapy after chemotherapy, concomitant administration of consolidative thoracic radiotherapy and protocol-specified prophylactic cranial irradiation with or without hippocampal avoidance is permitted.
* Patients must have a gadolinium contrast-enhanced three-dimensional (3D), spoiled gradient (SPGR), magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI scan. To yield acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR, MP-RAGE or TFE axial MRI scan must use the smallest possible axial slice thickness not exceeding 1.5 mm.

  * This MRI must be obtained within 56 days prior to Step 1 registration. Note: The MRI study is mandatory irrespective of randomization to the experimental or control arm of this study.
* Prior to chemotherapy +/- thoracic radiotherapy, patients must be defined as limited-stage or extensive-stage SCLC after clinical staging evaluation involving the following:

  1. History/physical examination;
  2. CT of the chest and abdomen with contrast (does not have to be done if the patient has had a positron emission tomography (PET) / CT scan prior to initiating chemotherapy or thoracic radiotherapy);
  3. MRI of the brain with contrast or diagnostic head CT with contrast;
  4. For patients without evidence of extensive-stage SCLC on chest and abdomen CT and brain MRI or head CT, a PET/CT or bone scan is required to confirm limited-stage SCLC.
* After chemotherapy, patients must be restaged prior to Step 1 registration using the same diagnostic work-up as required pre-chemotherapy. Repeat PET/CT or bone scan is not required. Patients must have:

  * History/physical examination within 30 days of Step 1 registration;
  * No CNS metastases (Repeat MRI required) within 56 days prior to Step 1 registration;
  * No progression in any site;
  * Radiographic partial or complete response to chemotherapy in at least one disease site within 56 days prior to Step 1 registration.

    1. If PET/CT was obtained prior to chemotherapy, either a repeat PET/CT or CT of the chest and abdomen with contrast can be obtained for response assessment.
    2. Patients who underwent resection for limited-stage SCLC prior to chemotherapy and have no radiographically evident disease for response assessment remain eligible if post-chemotherapy imaging demonstrates no progression.
* Zubrod performance status 0-2 within 30 days prior to Step 1 registration.
* Women of childbearing potential must have a negative qualitative serum pregnancy test =\< 14 days prior to Step 1 registration.
* Patients who are primary English or French speakers are eligible
* Patients must sign a study-specific informed consent prior to study entry

Inclusion Criteria \[prior to Step 2 registration\]:

* The following baseline neurocognitive assessments must be completed and uploaded within 10 calendar days after or at the time of Step 1 registration: HVLT-R (recall, delayed recall, and recognition), TMT (Parts A and B), and COWA. The neurocognitive assessments will be uploaded into the NRG Oncology Rave System for evaluation by Neurocognitive Co-Chair. Once the upload is complete, within 3 business days, a notification email will be sent to the site to proceed to Step 2 registration. At minimum, the HVLT-R delayed recall must be able to be scored (i.e. completed without error) in order to be eligible.
* Patients must have a baseline raw score greater than 2 on the HVLT-R delayed recall as determined by central assessment by the Neurocognitive Co-Chair.

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.

Primary outcomes:
measure: Number of Participants With Deterioration in HVLT-R Delayed Recall Score at Six Months (Phase III)
timeFrame: Baseline and six months
measure: Number of Participants With Intracranial Relapse at 12 Months (Phase II)
timeFrame: From baseline to 12 months
Secondary outcomes:
measure: Percentage of Participants With Neurocognitive Failure (Phase III)
timeFrame: 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.
measure: Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in HVLT-R Total Recall Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
timeFrame: Baseline, 3, 12 months.
measure: Number of Participants With Deterioration in HVLT-R Delayed Recall Score (Phase III)
timeFrame: Baseline, 18, 24 months.
measure: Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in HVLT-R Delayed Recognition Score (Phase III)
timeFrame: Baseline, 18, 24 months.
measure: Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in Trail Making Test (TMT) Part A (Phase III)
timeFrame: Baseline, 18, 24 months.
measure: Number of Participants With Deterioration in TMT Part B Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in TMT Part B Score (Phase III)
timeFrame: Baseline, 18, 24 months.
measure: Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in Controlled Oral Word Association (COWA) Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants by Highest Grade Adverse Event Reported (Phase III)
timeFrame: From start of treatment to last known follow-up . Maximum follow-up time was 7.2 years.
measure: 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)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Global Health Status (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Physical Functioning Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Role Functioning Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Emotional Functioning Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Social Functioning Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-C30 Cognitive Functioning Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC Quality of Life Questionnaire BN-20 (QLQ-BN20) Motor Dysfunction Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-BN20 Motor Dysfunction Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
timeFrame: Baseline, 3, 6, 12 months.
measure: Number of Participants With Deterioration in EORTC QLQ-BN20 Communication Deficit Score (Phase III)
timeFrame: Baseline,18, 24 months.
measure: Correlation of Quality of Life and Neurocognitive Function (NCF) Measures at 6 Months
timeFrame: 6 months
measure: Incremental Cost-per Quality-adjusted Life Year (QALY) (Cost-effectiveness as Measured by the EQ-5D (Phase III)
timeFrame: Baseline to two years
measure: Overall Survival (Phase III)
timeFrame: 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.
measure: Intracranial Relapse Rate (Phase III)
timeFrame: 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.
measure: White Matter Injury and Hippocampal Volume on Neurocognitive Function (Phase III)
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Tuscaloosa
country: United States
facility: Lewis and Faye Manderson Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Greenbrae
country: United States
facility: Marin General Hospital
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Merced
country: United States
facility: Mercy UC Davis Cancer Center
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland-Broadway
state: California
city: Orange
country: United States
facility: Saint Joseph Hospital - Orange
state: California
city: Rancho Cordova
country: United States
facility: Kaiser Permanente-Rancho Cordova Cancer Center
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Roseville
country: United States
facility: The Permanente Medical Group-Roseville Radiation Oncology
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Truckee
country: United States
facility: Gene Upshaw Memorial Tahoe Forest Cancer Center
state: California
city: Vallejo
country: United States
facility: Sutter Solano Medical Center/Cancer Center
state: California
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Bridgeport
country: United States
facility: Hartford HealthCare - Saint Vincent's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Coral Gables
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Coral Gables
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Cumming
country: United States
facility: Northside Hospital-Forsyth
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Savannah
country: United States
facility: Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
state: Georgia
city: 'Aiea
country: United States
facility: The Cancer Center of Hawaii-Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Boise
country: United States
facility: Saint Luke's Cancer Institute - Boise
state: Idaho
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Care Center-Caldwell
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Cancer Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Cancer Institute - Nampa
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Cancer Care Center-Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Cancer Institute - Twin Falls
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Hines
country: United States
facility: Edward Hines Jr VA Hospital
state: Illinois
city: Libertyville
country: United States
facility: Condell Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Anderson
country: United States
facility: Ascension Saint Vincent Anderson
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Muncie
country: United States
facility: IU Health Ball Memorial Hospital
state: Indiana
city: Cedar Rapids
country: United States
facility: Saint Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Cancer Center-Overland Park
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center/Weinberg Cancer Institute
state: Maryland
city: Baltimore
country: United States
facility: MedStar Good Samaritan Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Bel Air
country: United States
facility: UM Upper Chesapeake Medical Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology in Howard County
state: Maryland
city: Glen Burnie
country: United States
facility: UM Baltimore Washington Medical Center/Tate Cancer Center
state: Maryland
city: Ocean Pines
country: United States
facility: TidalHealth Richard A Henson Cancer Institute
state: Maryland
city: Salisbury
country: United States
facility: TidalHealth Peninsula Regional
state: Maryland
city: Towson
country: United States
facility: UM Saint Joseph Medical Center
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center - University Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Bay City
country: United States
facility: McLaren Cancer Institute-Bay City
state: Michigan
city: Brighton
country: United States
facility: Saint Joseph Mercy Brighton
state: Michigan
city: Brownstown
country: United States
facility: Henry Ford Cancer Institute-Downriver
state: Michigan
city: Chelsea
country: United States
facility: Saint Joseph Mercy Chelsea
state: Michigan
city: Clarkston
country: United States
facility: McLaren Cancer Institute-Clarkston
state: Michigan
city: Clarkston
country: United States
facility: Michigan Healthcare Professionals Clarkston
state: Michigan
city: Clinton Township
country: United States
facility: Henry Ford Macomb Hospital-Clinton Township
state: Michigan
city: Dearborn
country: United States
facility: Beaumont Hospital - Dearborn
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Healthcare Professionals Farmington
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute-Flint
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Grand Rapids
country: United States
facility: Trinity Health Grand Rapids Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lapeer
country: United States
facility: McLaren Cancer Institute-Lapeer Region
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Macomb
country: United States
facility: Michigan Healthcare Professionals Macomb
state: Michigan
city: Mount Clemens
country: United States
facility: McLaren Cancer Institute-Macomb
state: Michigan
city: Mount Pleasant
country: United States
facility: McLaren Cancer Institute-Central Michigan
state: Michigan
city: Muskegon
country: United States
facility: Trinity Health Muskegon Hospital
state: Michigan
city: Owosso
country: United States
facility: McLaren Cancer Institute-Owosso
state: Michigan
city: Petoskey
country: United States
facility: McLaren Cancer Institute-Northern Michigan
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: McLaren-Port Huron
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center Saint Joseph
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Troy
country: United States
facility: GenesisCare USA - Troy
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Albert Lea
country: United States
facility: Mayo Clinic Health System in Albert Lea
state: Minnesota
city: Duluth
country: United States
facility: Saint Luke's Hospital of Duluth
state: Minnesota
city: Mankato
country: United States
facility: Mayo Clinic Health Systems-Mankato
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Northfield
country: United States
facility: Mayo Clinic Radiation Therapy-Northfield
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: University of Kansas Cancer Center - North
state: Missouri
city: North Kansas City
country: United States
facility: University of Kansas Cancer Center at North Kansas City Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Dover
country: United States
facility: Wentworth-Douglass Hospital
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Mount Holly
country: United States
facility: Virtua Memorial
state: New Jersey
city: Voorhees
country: United States
facility: Virtua Voorhees
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bay Shore
country: United States
facility: Northwell Health Imbert Cancer Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Einstein Campus
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Brooklyn
country: United States
facility: New York-Presbyterian/Brooklyn Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Elmira
country: United States
facility: Arnot Ogden Medical Center/Falck Cancer Center
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Center for Advanced Medicine
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Staten Island
country: United States
facility: Staten Island University Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Pineville/LCI-Pineville
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health University City/LCI-University
state: North Carolina
city: Concord
country: United States
facility: Atrium Health Cabarrus/LCI-Concord
state: North Carolina
city: Monroe
country: United States
facility: Atrium Health Union/LCI-Union
state: North Carolina
city: Shelby
country: United States
facility: Atrium Health Cleveland/LCI-Cleveland
state: North Carolina
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Akron
country: United States
facility: Summa Health System - Akron Campus
state: Ohio
city: Akron
country: United States
facility: Cleveland Clinic Akron General
state: Ohio
city: Chardon
country: United States
facility: Geauga Hospital
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health Center West
state: Ohio
city: Dayton
country: United States
facility: Dayton Physician LLC-Miami Valley Hospital North
state: Ohio
city: Elyria
country: United States
facility: Mercy Cancer Center-Elyria
state: Ohio
city: Independence
country: United States
facility: Cleveland Clinic Cancer Center Independence
state: Ohio
city: Mentor
country: United States
facility: UH Seidman Cancer Center at Lake Health Mentor Campus
state: Ohio
city: Middleburg Heights
country: United States
facility: UH Seidman Cancer Center at Southwest General Hospital
state: Ohio
city: Parma
country: United States
facility: University Hospitals Parma Medical Center
state: Ohio
city: Strongsville
country: United States
facility: Cleveland Clinic Cancer Center Strongsville
state: Ohio
city: Westlake
country: United States
facility: UHHS-Westlake Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic Wooster Family Health and Surgery Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Broomall
country: United States
facility: Crozer-Keystone Regional Cancer Center at Broomall
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Dunmore
country: United States
facility: Northeast Radiation Oncology Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Glen Mills
country: United States
facility: Crozer Regional Cancer Center at Brinton Lake
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Media
country: United States
facility: Riddle Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Torresdale Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Reading
country: United States
facility: Penn State Health Saint Joseph Medical Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health-York Cancer Center
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Boiling Springs
country: United States
facility: Prisma Health Cancer Institute - Spartanburg
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Greenwood
country: United States
facility: Self Regional Healthcare
state: South Carolina
city: Hilton Head Island
country: United States
facility: The Radiation Oncology Center-Hilton Head/Bluffton
state: South Carolina
city: Lancaster
country: United States
facility: Lancaster Radiation Therapy Center
state: South Carolina
city: Rock Hill
country: United States
facility: Rock Hill Radiation Therapy Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Maryville
country: United States
facility: Blount Memorial Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: League City
country: United States
facility: UTMB Cancer Center at Victory Lakes
state: Texas
city: Ogden
country: United States
facility: Ogden Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center-North
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Wheeling
country: United States
facility: Wheeling Hospital/Schiffler Cancer Center
state: West Virginia
city: Antigo
country: United States
facility: Langlade Hospital and Cancer Center
state: Wisconsin
city: Brookfield
country: United States
facility: Ascension Southeast Wisconsin Hospital - Elmbrook Campus
state: Wisconsin
city: Eau Claire
country: United States
facility: Mayo Clinic Health System-Eau Claire Clinic
state: Wisconsin
city: Eau Claire
country: United States
facility: Mayo Clinic Health System Eau Claire Hospital-Luther Campus
state: Wisconsin
city: Franklin
country: United States
facility: Ascension Saint Francis - Reiman Cancer Center
state: Wisconsin
city: Grafton
country: United States
facility: Aurora Cancer Care-Grafton
state: Wisconsin
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Johnson Creek
country: United States
facility: UW Cancer Center Johnson Creek
state: Wisconsin
city: Kenosha
country: United States
facility: Aurora Cancer Care-Kenosha South
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System-Franciscan Healthcare
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Froedtert Menomonee Falls Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center
state: Wisconsin
city: Oshkosh
country: United States
facility: Vince Lombardi Cancer Clinic - Oshkosh
state: Wisconsin
city: Racine
country: United States
facility: Ascension All Saints Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Medical Center-River Region at Stevens Point
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Two Rivers
country: United States
facility: Vince Lombardi Cancer Clinic-Two Rivers
state: Wisconsin
city: Wausau
country: United States
facility: Aspirus Regional Cancer Center
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
city: Weston
country: United States
facility: Diagnostic and Treatment Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Medical Center - Weston
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Aspirus Cancer Care - Wisconsin Rapids
state: Wisconsin
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Health Centre at Southlake
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Research Institute of the McGill University Health Centre (MUHC)
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: NRG Oncology
name: Vinai Gondi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ishibashi A, Kurosaki H, Miura K, Utsumi N, Sakurai H. Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy. Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211045497. doi: 10.1177/15330338211045497.