Brain Tumor, Primary
Conditions
Brief summary
This is a pilot study to assess the changes in white matter, in the brain, in response to radiation therapy and correlate these changes with later declines in cognitive function.
Interventions
RADIATIONCranial Radiotherapy
Standard cranial radiotherapy administered dependent upon patient and brain tumor type.
DEVICEMRI with Diffusion Tensor Imaging (DTI)
Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI)
BEHAVIORALNeuro-cognitive Testing (CogState)
CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Pediatric patients (age 6-21) who will receive cranial radiotherapy for brian tumors. This could include but is not limited to: low grade glioma, high grade glioma (to include grade III but not grade IV glioma), germ cell tumors, primitive neuroectodermal tumors, craniopharyngioma, or medulloblastoma. * Patients should, in the estimate of the treating physician, be anticipated to have a median survival of greater than 1 year.
Exclusion criteria
* Patients with previous Central Nervous System (CNS) radiation or or CNS tumors that, in the judgement of the investigators, are likely to undergo progression during or shortly after radiotherapy are excluded. * Patients with glioblastoma, multiforme, gliosarcoma, diffuse pontine glioma, or other tumors presumed to have expected median survival per the investigators of less than 1 year. * Patients who require sedation for Magnetic Resonance Imagining (MRI)are excluded. * Patients at risk for nephrogenic systemic sclerosis will be excluded as a safety precaution due to the contrast used in the scans.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Change From Baseline in Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging (DTI) at 3 Weeks and at 6 Weeks Post Radiation Therapy. | Baseline, 3 weeks, and 6 weeks | Descriptive statistics and plots will be used to determine Diffusion Tensor Imaging (DTI) parameters for various regions in the brain. The mean (across subject) change in DTI parameter for a given region, at a given time, will be used to assess white matter injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Correlation Between Global COGState Scores and the Perpendicular Diffusivity of Water by Diffusion Tensor Imaging at Baseline, 3 Weeks, and 6 Weeks Into Treatment. | Baseline, 3 weeks, and 6 weeks | Determine the change in cognitive test scores from baseline to time-points early during radiation therapy (3 and 6 weeks) using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will be measurable even in this acute setting and will correlate with global response as measured on COGState with the sub-domains on executive function anticipated to be most highly correlated. |
| Evaluate the Correlation Between Global COGState Scores, Radiation Dose, and the Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging at 6 Months | 6 months | Determine the change in cognitive test scores from baseline, at 6 months using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints (Baseline and 6 months) using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis based upon results in adults treated with radiation therapy is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will correlate with changes in global response as measured on COGState with the sub-domains on executive function most highly correlated. In addition, these regional changes in DTI will be directly related to the radiation doses received in these regions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Primary Brain Tumor Patients receiving standard cranial radiotherapy will undergo (1) Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI) and (2) Neuro-cognitive testing (CogState-a computerized software testing system that offers various cognitive assessments based on traditional expansive neurocognitive tests) at four timepoints (Baseline, 3 weeks, 6 weeks and 6 months).
Cranial Radiotherapy: Standard cranial radiotherapy administered dependent upon patient and brain tumor type.
MRI with Diffusion Tensor Imaging (DTI): Magnetic Resonance Imaging (MRI) with Diffusion Tensor Imaging (DTI)
Neuro-cognitive Testing (CogState): CogState is a computerized software testing system that offers various cognitive assessments based traditional expansive neurocognitive tests. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Primary Brain Tumor |
|---|---|
| Age, Continuous | 14 years |
| Gender Female | 2 Participants |
| Gender Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Evaluate the Change From Baseline in Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging (DTI) at 3 Weeks and at 6 Weeks Post Radiation Therapy.
Descriptive statistics and plots will be used to determine Diffusion Tensor Imaging (DTI) parameters for various regions in the brain. The mean (across subject) change in DTI parameter for a given region, at a given time, will be used to assess white matter injury.
Time frame: Baseline, 3 weeks, and 6 weeks
Population: Because the outcome measure was CHANGE FROM BASELINE to 3 and 6 weeks, and data were not able to be collected at 3 and 6 weeks, the outcome measure could not be analyzed
Secondary
Evaluate the Correlation Between Global COGState Scores and the Perpendicular Diffusivity of Water by Diffusion Tensor Imaging at Baseline, 3 Weeks, and 6 Weeks Into Treatment.
Determine the change in cognitive test scores from baseline to time-points early during radiation therapy (3 and 6 weeks) using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will be measurable even in this acute setting and will correlate with global response as measured on COGState with the sub-domains on executive function anticipated to be most highly correlated.
Time frame: Baseline, 3 weeks, and 6 weeks
Population: Data can not be accessed due to technical difficulties with the COGState server.
Secondary
Evaluate the Correlation Between Global COGState Scores, Radiation Dose, and the Perpendicular Diffusivity of Water as Measured by Diffusion Tensor Imaging at 6 Months
Determine the change in cognitive test scores from baseline, at 6 months using CogState (a computerized software testing system that offers various cognitive assessments based on expansive neurocognitive tests). Correlate test scores from COGState with changes in Diffusion Tensor Imaging (DTI) at the same timepoints (Baseline and 6 months) using scatter plots with Pearson and Spearman's correlation coefficients. As a pilot study multiple comparisons will be assessed; however, the working hypothesis based upon results in adults treated with radiation therapy is that DTI changes as measured by an increase in diffusivity of water perpendicular to the direction of axonal transport will correlate with changes in global response as measured on COGState with the sub-domains on executive function most highly correlated. In addition, these regional changes in DTI will be directly related to the radiation doses received in these regions.
Time frame: 6 months
Population: Data can not be accessed due to technical difficulties with the COGState server.