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Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation

Completed
Conditions
Hodgkin Lymphoma
Interventions
Other: Neurocognitive Evaluation
Other: Quantitative Brain Imaging
Other: Neurologic Evaluation
Other: Health Questionnaire
Other: Vascular Testing
Other: Cardiopulmonary Exercise Testing
Other: Echocardiography
Other: Pulmonary Function Testing
Procedure: Serum Biomarkers
Other: Ophthalmology Examination
Registration Number
NCT01820117
Lead Sponsor
St. Jude Children's Research Hospital
Brief Summary

While thoracic radiation therapy (TRT) has been a primary component in successful treatment of a variety of childhood and adult cancers, the exposure to this treatment has been associated with significant cardiovascular and pulmonary morbidity in long-term survivors. Within non-cancer populations, cardiovascular and pulmonary morbidity is associated with increased risk for cerebral vascular accidents (CVAs), accelerated brain atrophy and neurocognitive impairment. Patients with chronic heart disease demonstrate problems with attention, processing speed, memory, and executive functions. Chronic pulmonary disease also increases the risk of stroke, leukoencephalopathy, and neurocognitive impairment in non-cancer populations. The investigators propose to examine indices of brain integrity, including neurocognitive performance and brain MRI/MRA, in long-term adult survivors of Hodgkin lymphoma (HL) treated with thoracic radiation and no direct central nervous system therapy.

OBJECTIVES:

1. To evaluate brain integrity in adult survivors of childhood HL treated with thoracic radiation therapy.

2. To identify therapeutic factors associated with brain integrity in adult survivors of childhood HL who are at risk for cardiac and pulmonary morbidity.

3. To examine associations between cardiac, vascular and pulmonary health and brain integrity in adult survivors of childhood HL treated with thoracic radiation.

Detailed Description

This is an observational study to collect health data from long-term survivors of Hodgkin lymphoma (HL). Data will be collected once at participant enrollment. The long-term effects of thoracic radiation therapy (TRT) given earlier as part of the treatment for HL will be examined in long-term survivors and compared to health data collected from normal volunteers.

HL survivors who were treated at St. Jude Children's Research Hospital (SJCRH) with TRT will be recruited to complete a comprehensive neurocognitive evaluation, brain MRI/MRA, a clinical neurological exam, peripheral pulse contour analysis, non-invasive central blood pressure monitoring, cardiopulmonary exercise testing, and serum biomarkers related to cardiac disease. As part of their standard St. Jude LIFE protocol evaluation, they also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

A comparison sample of healthy individuals, frequency-matched on age, sex and race will also be recruited. The comparison group will complete the comprehensive neurocognitive evaluation, brain MRI/MRA, clinical neurological exam, pulse contour analysis, non-invasive central blood pressure monitoring, and cardiopulmonary exercise testing. Through the St. Jude LIFE protocol, the comparison sample will also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
416
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Hodgkin lymphomaNeurologic EvaluationParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlQuantitative Brain ImagingA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaNeurocognitive EvaluationParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaHealth QuestionnaireParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaCardiopulmonary Exercise TestingParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaPulmonary Function TestingParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaSerum BiomarkersParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaOphthalmology ExaminationParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlSerum BiomarkersA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaQuantitative Brain ImagingParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaVascular TestingParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlNeurocognitive EvaluationA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlCardiopulmonary Exercise TestingA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlEchocardiographyA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlOphthalmology ExaminationA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Hodgkin lymphomaEchocardiographyParticipants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlNeurologic EvaluationA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlHealth QuestionnaireA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlVascular TestingA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Normal controlPulmonary Function TestingA group of healthy individuals matched for age, sex and race. Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.
Primary Outcome Measures
NameTimeMethod
Neurocognitive measures of sustained attention and memory between HL survivor group and control group.Once, at or near enrollment

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample t test will be conducted to compare the difference of neurocognitive impairment in area of sustained attention and memory in the HL survivors and matched controls.

Rate of leukoencephalopathy and hemosiderin deposits on quantitative MRI between HL survivor group and control group.Once, at or near enrollment

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample proportional test will be used to compare the rates of leukoencephalopathy and hemosiderin deposits between in the HL survivors and matched controls.

Rate of neurologic symptoms between HL survivor group and control group.Once, at or near enrollment

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample proportional test will be used to compare the rates of neurologic symptoms between the HL survivors and matched controls.

Secondary Outcome Measures
NameTimeMethod
Association between thoracic radiation dose and sustained attention and memory scores and rate of leukoencephalopathy and hemosiderin deposits in HL survivors.Once, at or near enrollment

In HL survivors only, outcome variables will be: sustained attention (continuous), memory (continuous), leukoencephalopathy (dichotomous) and hemosiderin deposits (dichotomous). Independent variables are radiation dose to cardiopulmonary structures. Covariates will include chemotherapy exposures, particularly anthracycline exposure. For each continuous response variable, linear regression model will be used to see its association with these independent variables, adjusted for race/age/sex. Other possible covariates include educational attainment, employment and occupation, current physical activity, and alcohol and tobacco. For each dichotomous response variable, logistic regression model will be used to see its association with these independent variables, adjusted for race/age/sex. AIC criteria will be used to select the final model.

Association between cardiac, vascular and pulmonary health and sustained attention and memory scores and rate of leukoencephalopathy and hemosiderin deposits.Once, at or near enrollment

In HL survivors only, outcome variables will be: sustained attention (continuous), memory (continuous), leukoencephalopathy (dichotomous) and hemosiderin deposits (dichotomous). Independent variables are cardiac, vascular and pulmonary health. For each continuous response variable, linear regression model will be used to see its association with these independent variables, adjusted for race/age/sex. Other possible covariates include educational attainment, employment and occupation, current physical activity, and alcohol and tobacco. For each dichotomous response variable, logistic regression model will be used to see its association with these independent variables, adjusted for race/age/sex. AIC criteria will be used to select the final model.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

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