Ignite Creation Date:
2024-07-17 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06466720
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-06-04
Brief Title:
Measuring and Mapping Cognitive Decline After Brain Radiosurgery
Sponsor:
University of Nottingham
Organization:
University of Nottingham
Study Overview
Official Title:
Measuring and Mapping Cognitive Decline After Brain Radiosurgery a Pilot Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CoDeB-Rad
Brief Summary:
Background Stereotactic Radiosurgery SRS is a localised radiotherapy treatment for patients with brain metastases or other benign tumours in the brain like meningiomas We do not currently know if or how much SRS affects brain function Patients with brain tumours do not get tested routinely for their brain function
Understanding short- and long-term side-effects is important for SRS Brain metastases patients have short life expectancies 6-months to 1-year However meningioma patients can live 10 years or more SRS is used to treat both
We will use the Montreal Cognitive Assessment MoCA to test your brain function We will use quality-of-life questionnaires QLQ-C30 and BN20 These are specific for patients with brain cancer They include questions about physical and mental wellbeing
Why is it important This study aims to identify areas in the brain that relate to changes in brain function after SRS These areas can then have the radiation dose reduced to them in future patients hoping to minimise side-effects
Research Question Which regions of the brain contribute to a decline in brain function following SRS
Study Design This is a single centre observational study with prospective and retrospective collection of data
This study will look at two groups of patients
Group1 Patients will complete the MoCA and two quality-of-life questionnaires before your treatment and every 3 months for a year
Group2 Patients will complete the MoCA and two quality-of-life questionnaires once
We will use these tests your MRI scans and your SRS treatment plan to identify areas of the brain that are responsible for any problems with your brain function
The participants for Group 1 will be recruited from the SRS Clinics at City Campus Nottingham University Hospitals NHS Trust
The participants for Group 2 will be identified through the Mosaiq Oncology Information System
This pilot study is funded by the Midlands Mental Health and Neurosciences Network
Understanding short- and long-term side-effects is important for SRS Brain metastases patients have short life expectancies 6-months to 1-year However meningioma patients can live 10 years or more SRS is used to treat both
We will use the Montreal Cognitive Assessment MoCA to test your brain function We will use quality-of-life questionnaires QLQ-C30 and BN20 These are specific for patients with brain cancer They include questions about physical and mental wellbeing
Why is it important This study aims to identify areas in the brain that relate to changes in brain function after SRS These areas can then have the radiation dose reduced to them in future patients hoping to minimise side-effects
Research Question Which regions of the brain contribute to a decline in brain function following SRS
Study Design This is a single centre observational study with prospective and retrospective collection of data
This study will look at two groups of patients
Group1 Patients will complete the MoCA and two quality-of-life questionnaires before your treatment and every 3 months for a year
Group2 Patients will complete the MoCA and two quality-of-life questionnaires once
We will use these tests your MRI scans and your SRS treatment plan to identify areas of the brain that are responsible for any problems with your brain function
The participants for Group 1 will be recruited from the SRS Clinics at City Campus Nottingham University Hospitals NHS Trust
The participants for Group 2 will be identified through the Mosaiq Oncology Information System
This pilot study is funded by the Midlands Mental Health and Neurosciences Network
Detailed Description:
Brain metastases affect roughly 20-40 of all cancer patients with a primary extracranial disease Lamba et at estimated that patients median survival without treatment is approximately one month This number increases from one month to between three and 12 months if whole brain radiotherapy WBRT is used WBRT is a radiotherapy treatment that is delivered in five to ten sessions and where the whole brain is irradiated With the advent of new systemic treatments prognosis for patients is constantly improving The widespread use of MRI imaging has also increased the number of patients being diagnosed by improving the detection of very small tumours one or two millimetres in diameter Consequently more people are referred for treatment with a curative intent for their brain metastases
Patients with brain metastases can be treated with surgery WBRT Stereotactic Radiosurgery SRS or a combination of the above SRS is the treatment of choice for single or multiple metastases unless there is a large mass more than 3 cm in diameter when surgery would be the preferred option This is due to the invasiveness of the surgery SRS is non or minimally invasive and the associated risks of having a surgical resection SRS is a highly focused treatment that makes use of stereotactic localisation techniques to deliver a high radiation dose to an outlined area of the brain The treatment is usually delivered in a single radiotherapy treatment In prospective randomised controlled trials it was shown that Stereotactic Radiosurgery is as effective as whole brain radiotherapy in terms of local tumour control but the burden of cognitive decline for the patients is less The primary tumours can vary but the majority of the patients have a lung breast melanoma kidney or colon primary
Radiation damages the brain with different areas being more or less susceptible to radiation The main organs used to optimise radiotherapy treatment plans by reducing the dose delivered to these include the eyes optic nerves chiasma brainstem cochleas lenses and lacrimal glands These are organs that affect physical functions Currently during radiotherapy treatment planning no consideration is given to areas of the brain that affect cognitive function such as the hippocampus basal ganglia insula and corpus callosum to name a few
The effects of radiotherapy in the brain are well documented but this is mostly for WBRT The effects of focal radiotherapy such as SRS on cognition have not been studied in detail This pilot study will be using voxel-based lesion symptom mapping VLSM to correlate the treatment planning dose maps with clinical outcomes on neurocognitive function
Voxel-based lesion symptom mapping is a technique where the relationship between damage to certain locations of the brain can be corelated with symptoms that affect cognitive function This is done on a voxel-by-voxel basis A voxel is a volume in a three-dimensional structure VLSM has been used extensively in the past in stroke patients but the literature is scarce for patients with brain metastases Individual MR images of the brain will be used along with the dose maps from each patients SRS treatment plan The dose maps will be overlayed and correlated with results from neurocognitive testing The identified areas of the brain will then be outlined and the dose level of significance the level of dose at which cognitive change becomes quantifiable will be assessed
Benefits
The identification of areas in the brain and associated doses with cognitive changes will help advise future guidelines on volumetric dose constraints for those areas in the brain As lesion location will be correlated with clinical outcomes from neurocognitive testing a better understanding of the side-effects of the radiotherapy treatment may be gained This will allow the optimisation of future radiotherapy treatments to spare these areas thereby minimising the side-effects of the radiotherapy treatment
Finally with the acquired knowledge consultants will be better placed to inform patients about the effects that their treatment will have Patients will therefore be able to make informed decisions about their treatment This is especially important in this population as the majority of patients treated with SRS do not have a very long life-expectancy
Methods Magnetic Resonance Imaging or MRI is a medical imaging technique that uses magnetic fields and radio waves to generate detailed images of the inside of the body MRI is the preferred imaging method used to diagnose tumours in the brain both benign and malignant due to its ability to provide high contrast for these tissues Tumours as small as 2 mm can be easily visualised with the aid of an MRI scanner
The methodology that will be used to analyse the data VLSM is well established and has been used extensively in patients with stroke lesions It uses a regression model that is univariate and can associate the cognitive performance of patients to whether or not a lesion is present in each voxel In this pilot study instead of using lesions we will be using the dose maps of the radiotherapy treatment plans
The structural MRI scans of the patients will be spatially normalised to a common coordinate system the Montreal Neurological Institute MNI space The transformations will then be used to fit the dose maps to the same coordinate system The data will then be smoothed The voxel-based lesion symptom mapping analysis will involve the use of a Matlab statistical parametric mapping toolbox For each voxel a group comparison between patients will be undertaken with the use of the dose maps from the radiotherapy treatment plans The t statistic will be computed based on the results from the neurocognitive testing A corresponding t-map of the brain will be created showing all the voxels related to the relevant cognitive deficits A correction for multiple comparisons needs to be carried out to ensure that the rate of false positives will be minimised
Patients with brain metastases can be treated with surgery WBRT Stereotactic Radiosurgery SRS or a combination of the above SRS is the treatment of choice for single or multiple metastases unless there is a large mass more than 3 cm in diameter when surgery would be the preferred option This is due to the invasiveness of the surgery SRS is non or minimally invasive and the associated risks of having a surgical resection SRS is a highly focused treatment that makes use of stereotactic localisation techniques to deliver a high radiation dose to an outlined area of the brain The treatment is usually delivered in a single radiotherapy treatment In prospective randomised controlled trials it was shown that Stereotactic Radiosurgery is as effective as whole brain radiotherapy in terms of local tumour control but the burden of cognitive decline for the patients is less The primary tumours can vary but the majority of the patients have a lung breast melanoma kidney or colon primary
Radiation damages the brain with different areas being more or less susceptible to radiation The main organs used to optimise radiotherapy treatment plans by reducing the dose delivered to these include the eyes optic nerves chiasma brainstem cochleas lenses and lacrimal glands These are organs that affect physical functions Currently during radiotherapy treatment planning no consideration is given to areas of the brain that affect cognitive function such as the hippocampus basal ganglia insula and corpus callosum to name a few
The effects of radiotherapy in the brain are well documented but this is mostly for WBRT The effects of focal radiotherapy such as SRS on cognition have not been studied in detail This pilot study will be using voxel-based lesion symptom mapping VLSM to correlate the treatment planning dose maps with clinical outcomes on neurocognitive function
Voxel-based lesion symptom mapping is a technique where the relationship between damage to certain locations of the brain can be corelated with symptoms that affect cognitive function This is done on a voxel-by-voxel basis A voxel is a volume in a three-dimensional structure VLSM has been used extensively in the past in stroke patients but the literature is scarce for patients with brain metastases Individual MR images of the brain will be used along with the dose maps from each patients SRS treatment plan The dose maps will be overlayed and correlated with results from neurocognitive testing The identified areas of the brain will then be outlined and the dose level of significance the level of dose at which cognitive change becomes quantifiable will be assessed
Benefits
The identification of areas in the brain and associated doses with cognitive changes will help advise future guidelines on volumetric dose constraints for those areas in the brain As lesion location will be correlated with clinical outcomes from neurocognitive testing a better understanding of the side-effects of the radiotherapy treatment may be gained This will allow the optimisation of future radiotherapy treatments to spare these areas thereby minimising the side-effects of the radiotherapy treatment
Finally with the acquired knowledge consultants will be better placed to inform patients about the effects that their treatment will have Patients will therefore be able to make informed decisions about their treatment This is especially important in this population as the majority of patients treated with SRS do not have a very long life-expectancy
Methods Magnetic Resonance Imaging or MRI is a medical imaging technique that uses magnetic fields and radio waves to generate detailed images of the inside of the body MRI is the preferred imaging method used to diagnose tumours in the brain both benign and malignant due to its ability to provide high contrast for these tissues Tumours as small as 2 mm can be easily visualised with the aid of an MRI scanner
The methodology that will be used to analyse the data VLSM is well established and has been used extensively in patients with stroke lesions It uses a regression model that is univariate and can associate the cognitive performance of patients to whether or not a lesion is present in each voxel In this pilot study instead of using lesions we will be using the dose maps of the radiotherapy treatment plans
The structural MRI scans of the patients will be spatially normalised to a common coordinate system the Montreal Neurological Institute MNI space The transformations will then be used to fit the dose maps to the same coordinate system The data will then be smoothed The voxel-based lesion symptom mapping analysis will involve the use of a Matlab statistical parametric mapping toolbox For each voxel a group comparison between patients will be undertaken with the use of the dose maps from the radiotherapy treatment plans The t statistic will be computed based on the results from the neurocognitive testing A corresponding t-map of the brain will be created showing all the voxels related to the relevant cognitive deficits A correction for multiple comparisons needs to be carried out to ensure that the rate of false positives will be minimised
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None