Neurococognitive and Functioal Assessment of Patients With Brain Metastases
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | March 2013 |
| Contact: | Meghan Wakefield, RN |
| Email: | meghan.wakefield@jefferson.edu |
| Phone: | 215-503-9110 |
Neurocognitive and fMRI Activation Changes Observed at Baseline and After Whole Brain Radiation vs. Radiosurgery for Patients With Cerebral Metastases: a Prospective Case-control Analysis.
The investigators seek to perform an observational study in patients with brain metastases
that are to undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)
treatment in order to quantify any baseline neurocognitive changes which may result from
intracranial disease burden, from radiation treatment (WBRT or SRS), or both. To do so, the
investigators will compare matched control subjects to patients at time points obtained
before and after radiation treatment with either SRS or WBRT. Pre-treatment evaluation will
include neurocognitive testing and an assessment of fMRI task-related activation patterns
and resting state brain activity. Four and twelve month post-treatment neuropsychological
evaluations will be performed and pre- and 4-month post-treatment fMRI scans will be
obtained in order to evaluate changes in neurocognitive functioning with a focus on
short-term memory and executive function domains. A brief quality of life assessment will
also be completed at each study time point. In order to plan treatment strategies in the
future it is important to accurately document the effects of intracranial disease burden as
well as radiation treatment on neurocognitive functioning, validate fMRI activation tasks
for short term memory and executive functioning, and quantify the activation volumes that
would potentially be spared in future "cognitive sparing" protocols.
The investigators hypothesize first that the amount and location of intracranial disease
burden will represent pre-treatment variables that affect NCF. The compromised NCF will be
visualized in both the resting state and task-oriented neurocognitive exercise. The
investigators anticipate that any perturbation in resting state caused by intracranial
disease burden should be reflected in patients when compared to matched controls.
The investigators hypothesize additionally that cancer patients with brain metastases
undergoing radiation treatments will have improved intracranial disease control at the
expense of executive and memory function with differences between patients that undergo
stereotactic radiosurgery or whole brain radiation alone.
that are to undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)
treatment in order to quantify any baseline neurocognitive changes which may result from
intracranial disease burden, from radiation treatment (WBRT or SRS), or both. To do so, the
investigators will compare matched control subjects to patients at time points obtained
before and after radiation treatment with either SRS or WBRT. Pre-treatment evaluation will
include neurocognitive testing and an assessment of fMRI task-related activation patterns
and resting state brain activity. Four and twelve month post-treatment neuropsychological
evaluations will be performed and pre- and 4-month post-treatment fMRI scans will be
obtained in order to evaluate changes in neurocognitive functioning with a focus on
short-term memory and executive function domains. A brief quality of life assessment will
also be completed at each study time point. In order to plan treatment strategies in the
future it is important to accurately document the effects of intracranial disease burden as
well as radiation treatment on neurocognitive functioning, validate fMRI activation tasks
for short term memory and executive functioning, and quantify the activation volumes that
would potentially be spared in future "cognitive sparing" protocols.
The investigators hypothesize first that the amount and location of intracranial disease
burden will represent pre-treatment variables that affect NCF. The compromised NCF will be
visualized in both the resting state and task-oriented neurocognitive exercise. The
investigators anticipate that any perturbation in resting state caused by intracranial
disease burden should be reflected in patients when compared to matched controls.
The investigators hypothesize additionally that cancer patients with brain metastases
undergoing radiation treatments will have improved intracranial disease control at the
expense of executive and memory function with differences between patients that undergo
stereotactic radiosurgery or whole brain radiation alone.
This research protocol is designed to perform neuropsychological testing and fMRI scanning
in patients with brain metastases that are to undergo either WBRT or SRS treatment at Thomas
Jefferson University Hospital. Eligible patients will be referred through the department of
Neurosurgery and Radiation-oncology. The patients will complete the informed consent for
both the pre- and post-treatment (4 month after WBRT or SRS is completed) fMRI scanning and
pre- and post-treatment (4 and 12 months after WBRT or SRS is completed) neuropsychological
testing sessions and be told that participation in either the fMRI scans and the
neuropsychological testing is voluntary. Patients will also be told that the data will be
collected for observational research purposes only and will not directly affect their
clinical care. Patients and their insurers will not be additionally billed as a consequence
of this study aside from the clinical billing that is consistent with current clinical
practice.
The fMRI study will be added on to the pre-existing treatment planning and follow up MRI
scan that would be obtained out of clinical necessity without the study.
In order to be able to identify and distinguish normal versus abnormal brain activity
patterns associated with the various fMRI tasks and resting state imaging procedures that
are part of this study, it will be necessary to scan a subset of healthy (age, education,
gender matched) normal controls on the various cognitive and behavioral tasks. This is the
only way to determine the validity of the tasks used in terms of their activation properties
and the normal brain areas involved in the task. Specifically, the healthy age matched
controls are critical for this study as there is no other way to validate the fMRI findings
with the hippocampal and executive function activations tasks. Normal matched controls are
needed for proper analysis of both the neurocognitive and the neuroimaging data. For the
neurocognitive data, the normal control data are needed to construct the Reliable Change
Index (RCI) referenced below in the Statistics Section. Also, a comparison to normal is
important for estimating the magnitude of any change observed in the patients, to determine
if it has clinical relevance. For the neuroimaging data, the normal controls are needed to
provide a reference or comparison point to quantify the degree to which the brain-imaging
map (referred to as a Statistical Parametric Map, SPM) at each point in time (baseline,
post-treatment) deviates from normal. By comparing the patient groups to normals, fMRI
activation related to ancillary or idiosyncratic factors during the scan cancel out, leaving
only the activation directly related to the cognitive task. Also, determining the presence
of new, atypical brain activation sites, lost activation sites, or deactivations, can only
be achieved by have a normal SPM brain map for comparison. This applies equally for the
task-driven fMRI and the resting state functional connectivity data.
To analyze within-subject analyses with the neuroimaging data, we will examine the
neuroimaging data on a within-subject but that will not be the primary quantitative approach
to the imaging data, as such within-subject comparisons can be prone to methodologic
problems. There is a phenomenon known in the neuroimaging literature as "double dipping"
which concerns the ability to distinguish real versus random variation over time. Double
dipping refers to the use of test findings at one point in time to constrain or bias the
data outcomes and changes registered at a second point in time. More concretely, differences
seen in the imaging data may reflect changes in the error, artifactual activations, not
change in true-task related activation. To avoid this problem we operationalize change by
comparing each patient's imaging data with an index of their deviation from healthy normals
at each point in time (pre-surgery/baseline, and post-surgery). This procedure provides a
systematic means of quantifying and then comparing the typicality of both pre and
postsurgical neurocognitive activations and network organization, a procedure that
alleviates concern about "double dipping". This "double dipping" phenomenon and the remedy
we propose applies equally for the task-driven fMRI, the resting state functional
connectivity data, and the DTI data.
In essence, the methodology proposed minimizes reliance on random, session-specific
fluctuations as part of the reference or comparison point for determining change. Our method
quantifies the deviation of our patients from normal, examining the relative difference in
those deviations as our index of change. In so doing, we avoid the use of our pre-treatment
neuroimaging results as the template for comparing and determining change, minimizing
concerns of double dipping.
There is no risk associated with the scanning procedure so long as there is no metal in the
body. The study of normal volunteers also allows for determination of the stability of the
activation findings over time; this allows for verification of the reliability of the fMRI
tasks and other procedures over time. Without an understanding of the potential normal
change that can occur in brain activation and structure over time, it is impossible to
determine if a pathologic change has occurred. This group of normal subjects will be studied
in advance in order to validate the fMRI tasks. Furthermore, normal control subjects will be
yoked or linked to matched patients and return for additional scanning sessions at the same
time points as their matched patient.
in patients with brain metastases that are to undergo either WBRT or SRS treatment at Thomas
Jefferson University Hospital. Eligible patients will be referred through the department of
Neurosurgery and Radiation-oncology. The patients will complete the informed consent for
both the pre- and post-treatment (4 month after WBRT or SRS is completed) fMRI scanning and
pre- and post-treatment (4 and 12 months after WBRT or SRS is completed) neuropsychological
testing sessions and be told that participation in either the fMRI scans and the
neuropsychological testing is voluntary. Patients will also be told that the data will be
collected for observational research purposes only and will not directly affect their
clinical care. Patients and their insurers will not be additionally billed as a consequence
of this study aside from the clinical billing that is consistent with current clinical
practice.
The fMRI study will be added on to the pre-existing treatment planning and follow up MRI
scan that would be obtained out of clinical necessity without the study.
In order to be able to identify and distinguish normal versus abnormal brain activity
patterns associated with the various fMRI tasks and resting state imaging procedures that
are part of this study, it will be necessary to scan a subset of healthy (age, education,
gender matched) normal controls on the various cognitive and behavioral tasks. This is the
only way to determine the validity of the tasks used in terms of their activation properties
and the normal brain areas involved in the task. Specifically, the healthy age matched
controls are critical for this study as there is no other way to validate the fMRI findings
with the hippocampal and executive function activations tasks. Normal matched controls are
needed for proper analysis of both the neurocognitive and the neuroimaging data. For the
neurocognitive data, the normal control data are needed to construct the Reliable Change
Index (RCI) referenced below in the Statistics Section. Also, a comparison to normal is
important for estimating the magnitude of any change observed in the patients, to determine
if it has clinical relevance. For the neuroimaging data, the normal controls are needed to
provide a reference or comparison point to quantify the degree to which the brain-imaging
map (referred to as a Statistical Parametric Map, SPM) at each point in time (baseline,
post-treatment) deviates from normal. By comparing the patient groups to normals, fMRI
activation related to ancillary or idiosyncratic factors during the scan cancel out, leaving
only the activation directly related to the cognitive task. Also, determining the presence
of new, atypical brain activation sites, lost activation sites, or deactivations, can only
be achieved by have a normal SPM brain map for comparison. This applies equally for the
task-driven fMRI and the resting state functional connectivity data.
To analyze within-subject analyses with the neuroimaging data, we will examine the
neuroimaging data on a within-subject but that will not be the primary quantitative approach
to the imaging data, as such within-subject comparisons can be prone to methodologic
problems. There is a phenomenon known in the neuroimaging literature as "double dipping"
which concerns the ability to distinguish real versus random variation over time. Double
dipping refers to the use of test findings at one point in time to constrain or bias the
data outcomes and changes registered at a second point in time. More concretely, differences
seen in the imaging data may reflect changes in the error, artifactual activations, not
change in true-task related activation. To avoid this problem we operationalize change by
comparing each patient's imaging data with an index of their deviation from healthy normals
at each point in time (pre-surgery/baseline, and post-surgery). This procedure provides a
systematic means of quantifying and then comparing the typicality of both pre and
postsurgical neurocognitive activations and network organization, a procedure that
alleviates concern about "double dipping". This "double dipping" phenomenon and the remedy
we propose applies equally for the task-driven fMRI, the resting state functional
connectivity data, and the DTI data.
In essence, the methodology proposed minimizes reliance on random, session-specific
fluctuations as part of the reference or comparison point for determining change. Our method
quantifies the deviation of our patients from normal, examining the relative difference in
those deviations as our index of change. In so doing, we avoid the use of our pre-treatment
neuroimaging results as the template for comparing and determining change, minimizing
concerns of double dipping.
There is no risk associated with the scanning procedure so long as there is no metal in the
body. The study of normal volunteers also allows for determination of the stability of the
activation findings over time; this allows for verification of the reliability of the fMRI
tasks and other procedures over time. Without an understanding of the potential normal
change that can occur in brain activation and structure over time, it is impossible to
determine if a pathologic change has occurred. This group of normal subjects will be studied
in advance in order to validate the fMRI tasks. Furthermore, normal control subjects will be
yoked or linked to matched patients and return for additional scanning sessions at the same
time points as their matched patient.
Inclusion Criteria:
- Patients with a cumulative intracranial disease burden of up to but not exceeding
8cc.
- Patients with newly diagnosed brain metastases are undergoing WBRT or SRS as
previously determined by their oncologist and or radiation oncologist.
- Right or left hand dominance.
- Karnofsky performance status (KPS) equal to or greater than 70.
- 70 years old or younger.
- All non-hematopoietic histologies except melanoma and renal cell carcinoma.
- Brainstem lesions are acceptable.
- Normal renal function to tolerate a contrast enhanced MRI scan.
- Patients must provide study specific informed consent prior to study entry.
Exclusion Criteria:
- Age less than 18 years old.
- KPS <70.
- Pregnant female.
- Active systemic disease.
- Age greater than 70 years old.
- Patients with leptomeningeal metastases.
- Contraindication for MRI such as implanted metal devices, foreign bodies or severe
claustrophobia or axial back pain precluding a prolonged MRI study.
- Prior radiation therapy to the brain.
- Poor renal function rendering contrast enhanced MRI un-obtainable.
- Histological diagnosis of small cell lung cancer.
- Craniotomy or other major surgery within 2 weeks of start of either SRS or WBRT.
We found this trial at
1
site
Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
Click here to add this to my saved trials
