Neoplasms

All Conditions

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Subjects with a histological diagnosis of malignancy of the base of skull necessitating irradiation to a minimum of 60 Gy, ECOG PS 0-1 with no evidence of metastatic disease and an estimate life expectancy of at least 1 year and who is able to provide informed consent. Subjects will undergo standard CT simulation and radiotherapy treatment planning.

Subjects with a histological diagnosis of low grade glioma requiring radiotherapy. ECOG PS 0-1 with no evidence of metastatic disease and an estimated life expectancy of at least 1 year and who is able to provide informed consent. Subjects will undergo standard CT simulation and radiotherapy treatment planning.

10 of the 30 subjects on Cohort 1 will receive photon treatment plans.

Photon treatment plans

20 subjects from Cohort 1 will receive proton treatment plans with malignancies involving the base of skull.

Proton Treatment Plans

Verbal and Visual memory; immediate attention, working memory, and processing speed; executive functions and affect and depression.

Neurocognitive evaluation

Anatomic Imaging, Blood volume measurements, Diffusion Tensor Imaging, DTI Image Processing

Advanced MRI imaging

Michelle Alonso Basanta, MD

The purpose of this study is to:

* estimate the degree of memory loss, if any following radiotherapy to the base of skull or brain as measured by standard neurocognitive battery testing.
* describe radiotherapy dose-related changes in vascular perfusion, in spectroscopic parameters of neuronal injury and changes in the degree and directionality of tissue water diffusivity (diffusion tensor imaging) as a measure of white axonal injury.
* to relate these imaging characteristics to the degree of memory loss.

Data suggests that regions of the normal brain exposed to radiation doses that has otherwise been regarded as safe and not limited by current radiation treatment planning may contribute to the risk of late neurocognitive injury. Radiation dose-dependent subclinical vascular effects have been reported in irradiated normal brain tissue and have been hypothesized to be a potential mechanism of action. Direct neuronal injury is another potential mechanism of injury. 1)Estimate the degree of cognitive loss following RT. 2) Demonstrate evidence of radiation induced subclinical vascular and neuronal injury in adjacent brain regions receiving exit doses of radiation. Subjects will include patients with malignancies of the skull of the skull base or patients with low grade glioma who require radiotherapy. Baseline MRI imaging of the brain utilizing established techniques will be used to identify and characterize the regions of interest anatomically adjacent to the regions of intended high dose irradiation. The MRI data for the ROIs will be registered with the radiotherapy treatment planning CT in order to create a single volume of data where each voxel corresponds to a vector containing the multi-parametric information. Subsequent repeat MRI imaging will be at 1.5, 4.5, 12 and 24 months following completion of the radiotherapy for patients with low grade glioma and 1.5 and 12 months post radiotherapy for patients with malignancies involving the skull base. Both cohorts will repeat standard neurocognitive evaluation at 1.5, 4.5,12 and 24 months following completion of radiotherapy. Analysis: Neurocognitive domains will be evaluated at the designated time points.

Skull Base and Low Grade Glioma Neurocognitive Magnetic Resonance Imaging (MRI) Study

Detection of Vascular and Neuronal Changes Following Proton and/or Photon Radiotherapy in Patients Receiving Skull Base and/or Brain Radiation

verbal and visual memory; immediate attention, working memory, and processing speed; executive functions and affect and depression

United States Department of Defense

Abramson Cancer Center at Penn Medicine

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Hodgkin Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

All Drugs and Chemicals

Carbon Monoxide

Participants 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.

A 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.

The neurocognitive evaluation will include measures of academic achievement, intelligence, sustained attention, memory, processing speed, executive functions, functional behavior, and emotional functioning.

Neurocognitive Evaluation

Imaging will include raw images to both quantify white matter hyperintensities and hemosiderin deposits, as well as cortical thickness and tissue segmentation. Brain imaging will be repeated on participants who are concurrently enrolled on BRIGHT and MIND protocols at St. Jude and who completed prior brain imaging during the BRIGHT clinic visit. The repeat MRI will be done at their 6 month MIND clinic visit.

Quantitative Brain Imaging

Evaluation includes a complete review of neurologic symptoms, and interview and examination by the neurologist, assessment of neurologic symptoms and determination of their impact on day-to-day living, and quantified neurologic examination by the neurologist.

Neurologic Evaluation

Participants will be asked to complete an approximately 450-item survey to assess health history and status, social and demographic factors, health behaviors, and psychosocial constructs.

Health Questionnaire

Digital assessment of endothelial function will be studied, and central blood and pulse pressure and carotid-femoral pulse wave velocity will be non-invasively measured.

Vascular Testing

Study participants will undergo cardiopulmonary exercise testing by treadmill. Those participants whose physical performance does not permit walking safely on the treadmill (extreme deconditioning, lower extremity paralysis, balance disorder, acute lower extremity injury) will perform cardiopulmonary exercise testing on a bicycle or upper extremity ergometer using a comparable testing protocol.

Cardiopulmonary Exercise Testing

A complete 3D as well as 2D echocardiogram with Doppler and M-mode will be performed.

Echocardiography

Pulmonary function testing will include spirometry, lung volume measurements by body plethysmography, and single-breath carbon monoxide-diffusion capacity (DLCO).

Pulmonary Function Testing

Blood for serum biomarkers associated with cardiovascular morbidity will be drawn, including high-sensitivity C-reactive protein, serum homocysteine.

Serum Biomarkers

Ophthalmology examination will include a review of symptoms, examination, and fundus imaging. The examination will consist of visual acuity testing, refraction testing, retinoscopy, ocular pressure, and examination under mydriasis. Fundus photography will be used to capture an image of the retina for examination of potential hypertensive retinopathy.

Ophthalmology Examination

Kevin Krull, PhD

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.

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.

Blood (5 ml) will be collected, frozen and stored for future serum biomarker assays.

Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation

Brain Integrity in Survivors of Hodgkin Lymphoma (HL) Treated With Thoracic Radiation

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Skull Base and Low Grade Glioma Neurocognitive Magnetic Resonance Imaging (MRI) Study	NCT01212731	Malignancy Glioma Radiotherapy	Photon treatmen... Proton Treatmen... Neurocognitive ... Advanced MRI im...	18 Years -	Abramson Cancer Center at Penn Medicine
Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation	NCT01820117	Hodgkin Lymphom...	Neurocognitive ... Quantitative Br... Neurologic Eval... Health Question... Vascular Testin... Cardiopulmonary... Echocardiograph... Pulmonary Funct... Serum Biomarker... Ophthalmology E...	18 Years -	St. Jude Children's Research Hospital

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