Clinical trial NCT01820117: Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation
Official title: Brain Integrity in Survivors of Hodgkin Lymphoma (HL) Treated With Thoracic Radiation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hodgkin Lymphoma
Keywords: long-term health outcomes
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-03-28
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: SJLIFE is an institutional initiative to establish a lifetime survivor cohort to study physical and behavioral health outcomes in adult survivors of childhood cancer. This protocol includes individuals diagnosed and treated with a malignancy during childhood at SJCRH since 1962, who are now 10 or more years from diagnosis and over 18 years of age.

The current study will recruit participants from the SJLIFE cohort who received thoracic radiation as part of their treatment for Hodgkin lymphoma.

Potentially eligible comparison group participants will be recruited from the relative or friend population who accompany any After Completion of Therapy (ACT) or SJLIFE patient for follow-up at SJCRH.

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.

Eligibility criteria: Inclusion Criteria - HL participant:

* Current St. Jude LIFE protocol Participant, treated with thoracic radiation
* Currently ≥ 18 years of age
* ≥ 10 years from original diagnosis

Exclusion Criteria - HL participant:

* Has participated in the previous pilot study at St. Jude (HPP16)
* History of cranial or total-body radiation therapy
* History of intrathecal Methotrexate, high-dose Methotrexate or high-dose Cytarabine.
* History of head injury or diagnosis of a genetic disorder associated with neurocognitive impairment
* Pre-existing known neurocognitive impairment prior to diagnosis of Hodgkin lymphoma
* History of congenital heart disease reported in the literature to be associated with neurocognitive status as determined by the principal investigators
* Currently pregnant
* Secondary central nervous system neoplasm

Inclusion Criteria - Normal Control:

* Research participant is a sibling, parent, relative or friend of a current or former St. Jude patient
* Research participant must be at least 18 years of age at the time of the scheduled evaluation

Exclusion Criteria - Normal Control:

* History of cranial, total-body or thoracic radiation therapy
* History of intrathecal Methotrexate, high-dose Methotrexate, or high-dose Cytarabine.
* History of head injury or diagnosis of a genetic disorder associated with neurocognitive impairment
* Known neurocognitive impairment
* History of congenital heart disease reported in the literature to be associated with neurocognitive status as determined by the principal investigators
* Currently pregnant
* Central nervous system neoplasm

Primary outcomes:
measure: Neurocognitive measures of sustained attention and memory between HL survivor group and control group.
timeFrame: Once, at or near enrollment
measure: Rate of leukoencephalopathy and hemosiderin deposits on quantitative MRI between HL survivor group and control group.
timeFrame: Once, at or near enrollment
measure: Rate of neurologic symptoms between HL survivor group and control group.
timeFrame: Once, at or near enrollment
Secondary outcomes:
measure: Association between thoracic radiation dose and sustained attention and memory scores and rate of leukoencephalopathy and hemosiderin deposits in HL survivors.
timeFrame: Once, at or near enrollment
measure: Association between cardiac, vascular and pulmonary health and sustained attention and memory scores and rate of leukoencephalopathy and hemosiderin deposits.
timeFrame: Once, at or near enrollment
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Kevin Krull, PhD
role: PRINCIPAL_INVESTIGATOR
References: