Brain MetastasesCoDeB-RadNCT06466720
Measuring and Mapping Cognitive Decline After Brain Radiosurgery
An observational study of Brain Metastases and Meningiomas, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Background Stereotactic Radiosurgery (SRS) is a localised radiotherapy treatment for patients with brain metastases or other benign tumours in the brain, like meningiomas. The Investigators do not currently know if, or how much, SRS affects brain function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Meningiomas, Stereotactic Radiosurgery
- What is being tested?
- Neurocognitive testing, Quality of Life questionnaire and Stereotactic radiosurgery
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jun 2024to 30 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The population is based within the East Midlands, United Kingdom. The East Midlands Stereotactic Radiosurgery (SRS) service covers Nottinghamshire, Derbyshire, Lincolnshire and Leicestershire. Any patients that are eligible for SRS (prospective cohort) or has already been treated with SRS (retrospective cohort) and also fulfil the eligibility criteria of the study will be invited to take part in the study. Patients will be recruited through the SRS clinics taking place at City Campus, Nottingham University Hospitals NHS Trust.
Who may be able to join
- Patients will be eligible for inclusion only if ALL of the following criteria apply:
- Age: above 18 years, no upper limit
- Diagnosis of brain metastases or meningioma, where the treatment is going to be stereotactic radiosurgery
- Karnofsky Performance Status (KPS) ≥70
- Established diagnosis of cancer with absent or controllable primary disease
- Tumour volume of less than 20cc
Show all 14Show fewer
- Life expectancy of more than 6 months
- Able to give informed consent
- Patients will be eligible for inclusion only if ALL of the following criteria apply:
- Age: above 18 years, no upper limit
- Diagnosis of meningioma
- Previous SRS treatment at least 1 year prior to inclusion in the study
- Most recent MRI scan (within 1 year) shows stable appearances
- Able to give informed consent
Who cannot join
- Previous RT to the brain, including SRS
- Previous surgery to the brain
- Not willing or not able to give informed consent
- Previous RT to the brain, excluding SRS
- Previous surgery to the brain
- Not willing or not able to give informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, NG5 1 PB
About this study
Official title: Measuring and Mapping Cognitive Decline After Brain Radiosurgery: a Pilot Study
Background Stereotactic Radiosurgery (SRS) is a localised radiotherapy treatment for patients with brain metastases or other benign tumours in the brain, like meningiomas. The Investigators 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.
Read more
The Montreal Cognitive Assessment will be used to test the participants' brain function. Quality-of-life questionnaires QLQ-C30 and BN20 will also be used to assess the participants' physical and mental wellbeing . These are specific for patients with brain cancer.
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 the treatment and every 3 months for a year.
Group2: Patients will complete the MoCA and two quality-of-life questionnaires once.
The investigators will use these tests, MRI scans and the SRS treatment plan to identify areas of the brain that are responsible for any problems with the participants' 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.
Read the 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 patient's 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 the investigators 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.
- Conditions
- Brain Metastases, Meningiomas, Stereotactic Radiosurgery, Cognitive Decline, Quality of Life, SRS
- Being tested
- Neurocognitive testing, Quality of Life questionnaire, Stereotactic radiosurgery
- Keywords
- Brain metastases, Meningiomas, Stereotactic Radiosurgery, SRS, Cognitive Decline, Quality of Life
- Medical subject headings
- Brain Neoplasms, Meningioma, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurocognitive testingBehavioural
Also called Montreal Cognitive Assessment
The MoCA is a brief tool developed to screen mild cognitive impairment and has been validated in patients aged 55-85 years old. It has been tested and validated in patients with brain metastases, and its acceptability has been tested in the general brain tumour population. The paper version of the MoCA is available in nearly 100 languages. The online version is available currently in 5 languages.
Quality of Life questionnaireBehavioural
Also called QLQ-C30, QLQ-BN20
The EORTC-QLQ-C30 is a quality-of-life questionnaire that was developed by the European Organisation for Research and Treatment of Cancer (EORTC) for use in clinical trials. It is a 30-item questionnaire that incorporates the following five scales: physical, role, cognitive, emotional and social. It has also been validated and is available in more than 100 languages. The EORTC-QLQ-BN20 is a questionnaire that was developed for use specifically with patients that have brain cancer. The BN20 is a 20-item questionnaire and addresses four different scales (multi-item): future uncertainty, visual disorder, motor dysfunction and communication deficit. There are seven items that assess physical symptoms: headaches, seizures, drowsiness, hair loss, itchy skin, weakness of legs and bladder control. The questionnaire has been validated in over 15 languages. The two questionnaires are meant to complement each other when used in patients with brain cancer.
Stereotactic radiosurgeryRadiation
Also called SRS
This is a Standard of Care treatment for all the patients that will be recruited in both cohorts. Stereotactic radiosurgery will be delivered to one or more sites and in the prospective cohort can be delivered more than once.
| Study group | Role | What they receive |
|---|---|---|
| Prospective | Patients with brain metastases and meningiomas that are eligible for SRS treatment will be included in the prospective arm of the trial. The patients will have neurocognitive testing in the form of the Montreal Cognitive Assessment (MoCA) and will answer two Quality of Life questionnaires (QLQs) by EORTC QLQ-C30 and BN20). The baseline visit will happen before they start their SRS treatment.
The patients will be seen an additional 4 times, at 3, 6, 9 and 12 months after radiotherapy treatment. During each visit they will complete the MoCA and the QLQs.
During the first follow up appointment they will also be asked to think back to before they had the treatment and answer the QLQs based on that. Receives: Behavioral: Neurocognitive testing; Behavioral: Quality of Life questionnaire; Radiation: Stereotactic radiosurgery | |
| Retrospective | Patients with meningiomas that have received SRS treatment more than a year ago will be included in the retrospective arm of the trial. The patients will have neurocognitive testing in the form of the Montreal Cognitive Assessment (MoCA) and will answer two Quality of Life questionnaires (QLQs) by EORTC QLQ-C30 and BN20) once. They will also be asked to think back to before they had the treatment and answer the QLQs based on that. Receives: Behavioral: Neurocognitive testing; Behavioral: Quality of Life questionnaire; Radiation: Stereotactic radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline to neurocognitive function and Quality of Life at 6 months
Significant changes in neurocognitive function and Quality of Life at 6 months compared to baseline.The scale ranges from 0-100 with 0 signifying a worse quality of life and 100 signifying excellent quality of life for the participants. The cognitive function scale ranges from 0-30 with 30 signifying non-impaired cognitive function.
Measured: 6 months
Doses related to neurocognitive symptoms
- Doses above which the lesion symptom mapping identifies areas of the brain relevant to neurocognitive symptoms at 6 months.
Measured: 6 months
Secondary outcomes (2)
Recruitment feasibility
The number of patients screened versus the number of patients recruited will be recorded along with any reasons for non-participation
Measured: 1.5 years
Patient reported symptoms vs symptoms identified by neurocognitive testing
- Do patient reported symptoms relate to those identified from neurocognitive testing.
Measured: At baseline and every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2024
- Study start21 Jun 2024
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Sponsor
- Investigators
- Paul S Morgan, Professor of Medical Physics, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06466720
- Sponsor's protocol ID
- 24016
- Acronym
- CoDeB-Rad
- Status last verified
- Apr 2026
- First submitted
- 4 Jun 2024
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lamba N, Muskens IS, DiRisio AC, Meijer L, Briceno V, Edrees H, Aslam B, Minhas S, Verhoeff JJC, Kleynen CE, Smith TR, Mekary RA, Broekman ML. Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis. Radiat Oncol. 2017 Jun 24;12(1):106. doi: 10.1186/s13014-017-0840-x.
PubMed 28646895Lippitz B, Lindquist C, Paddick I, Peterson D, O'Neill K, Beaney R. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treat Rev. 2014 Feb;40(1):48-59. doi: 10.1016/j.ctrv.2013.05.002. Epub 2013 Jun 27.
PubMed 23810288Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF. Voxel-based lesion-symptom mapping. Nat Neurosci. 2003 May;6(5):448-50. doi: 10.1038/nn1050. No abstract available.
PubMed 12704393Glascher J, Tranel D, Paul LK, Rudrauf D, Rorden C, Hornaday A, Grabowski T, Damasio H, Adolphs R. Lesion mapping of cognitive abilities linked to intelligence. Neuron. 2009 Mar 12;61(5):681-91. doi: 10.1016/j.neuron.2009.01.026.
PubMed 19285465Geva S, Baron JC, Jones PS, Price CJ, Warburton EA. A comparison of VLSM and VBM in a cohort of patients with post-stroke aphasia. Neuroimage Clin. 2012 Aug 30;1(1):37-47. doi: 10.1016/j.nicl.2012.08.003. eCollection 2012.
PubMed 24179735Taphoorn MJ, Claassens L, Aaronson NK, Coens C, Mauer M, Osoba D, Stupp R, Mirimanoff RO, van den Bent MJ, Bottomley A; EORTC Quality of Life Group, and Brain Cancer, NCIC and Radiotherapy Groups. An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. Eur J Cancer. 2010 Apr;46(6):1033-40. doi: 10.1016/j.ejca.2010.01.012. Epub 2010 Feb 22.
PubMed 20181476Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
PubMed 15817019Meyer S, Kessner SS, Cheng B, Bonstrup M, Schulz R, Hummel FC, De Bruyn N, Peeters A, Van Pesch V, Duprez T, Sunaert S, Schrooten M, Feys H, Gerloff C, Thomalla G, Thijs V, Verheyden G. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits. Neuroimage Clin. 2015 Dec 11;10:257-66. doi: 10.1016/j.nicl.2015.12.005. eCollection 2016.
PubMed 26900565Renovanz M, Reitzug L, Messing L, Scheurich A, Gruninger S, Ringel F, Coburger J. Patient reported feasibility and acceptance of Montreal Cognitive Assessment (MoCA) screening pre- and postoperatively in brain tumour patients. J Clin Neurosci. 2018 Jul;53:79-84. doi: 10.1016/j.jocn.2018.04.034. Epub 2018 Apr 20.
PubMed 29685411Olson RA, Iverson GL, Carolan H, Parkinson M, Brooks BL, McKenzie M. Prospective comparison of two cognitive screening tests: diagnostic accuracy and correlation with community integration and quality of life. J Neurooncol. 2011 Nov;105(2):337-44. doi: 10.1007/s11060-011-0595-4. Epub 2011 Apr 26.
PubMed 21520004Olson RA, Chhanabhai T, McKenzie M. Feasibility study of the Montreal Cognitive Assessment (MoCA) in patients with brain metastases. Support Care Cancer. 2008 Nov;16(11):1273-8. doi: 10.1007/s00520-008-0431-3. Epub 2008 Mar 12.
PubMed 18335256Yang Y, Tompkins CA, Meigh KM, Prat CS. Voxel-Based Lesion Symptom Mapping of Coarse Coding and Suppression Deficits in Patients With Right Hemisphere Damage. Am J Speech Lang Pathol. 2015 Nov;24(4):S939-52. doi: 10.1044/2015_AJSLP-14-0149.
PubMed 26425785Baldo JV, Schwartz S, Wilkins D, Dronkers NF. Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping. J Int Neuropsychol Soc. 2006 Nov;12(6):896-900. doi: 10.1017/S1355617706061078.
PubMed 17064451DeMarco AT, Turkeltaub PE. A multivariate lesion symptom mapping toolbox and examination of lesion-volume biases and correction methods in lesion-symptom mapping. Hum Brain Mapp. 2018 Nov;39(11):4169-4182. doi: 10.1002/hbm.24289. Epub 2018 Jul 4.
PubMed 29972618Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, Maor MH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Nov;10(11):1037-44. doi: 10.1016/S1470-2045(09)70263-3. Epub 2009 Oct 2.
PubMed 19801201
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measuring and Mapping Cognitive Decline After Brain Radiosurgery: a Pilot Study
- ClinicalTrials.gov ID
- NCT06466720
- Acronym / sponsor ID
- CoDeB-Rad / 24016
- Conditions
- Brain Metastases, Meningiomas, Stereotactic Radiosurgery, Cognitive Decline, Quality of Life, SRS
- Keywords
- Brain metastases, Meningiomas, Stereotactic Radiosurgery, SRS, Cognitive Decline, Quality of Life
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- 21 Jun 2024 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 20 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background Stereotactic Radiosurgery (SRS) is a localised radiotherapy treatment for patients with brain metastases or other benign tumours in the brain, like meningiomas. The Investigators 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.
The Montreal Cognitive Assessment will be used to test the participants' brain function. Quality-of-life questionnaires QLQ-C30 and BN20 will also be used to assess the participants' physical and mental wellbeing . These are specific for patients with brain cancer.
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 the treatment and every 3 months for a year.
Group2: Patients will complete the MoCA and two quality-of-life questionnaires once.
The investigators will use these tests, MRI scans and the SRS treatment plan to identify areas of the brain that are responsible for any problems with the participants' 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 patient's 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 the investigators 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 design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospective | – | Behavioral: Neurocognitive testing, Behavioral: Quality of Life questionnaire, Radiation: Stereotactic radiosurgeryPatients with brain metastases and meningiomas that are eligible for SRS treatment will be included in the prospective arm of the trial. The patients will have neurocognitive testing in the form of the Montreal Cognitive Assessment (MoCA) and will answer two Quality of Life questionnaires (QLQs) by EORTC QLQ-C30 and BN20). The baseline visit will happen before they start their SRS treatment. The patients will be seen an additional 4 times, at 3, 6, 9 and 12 months after radiotherapy treatment. During each visit they will complete the MoCA and the QLQs. During the first follow up appointment they will also be asked to think back to before they had the treatment and answer the QLQs based on that. |
| Retrospective | – | Behavioral: Neurocognitive testing, Behavioral: Quality of Life questionnaire, Radiation: Stereotactic radiosurgeryPatients with meningiomas that have received SRS treatment more than a year ago will be included in the retrospective arm of the trial. The patients will have neurocognitive testing in the form of the Montreal Cognitive Assessment (MoCA) and will answer two Quality of Life questionnaires (QLQs) by EORTC QLQ-C30 and BN20) once. They will also be asked to think back to before they had the treatment and answer the QLQs based on that. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The population is based within the East Midlands, United Kingdom. The East Midlands Stereotactic Radiosurgery (SRS) service covers Nottinghamshire, Derbyshire, Lincolnshire and Leicestershire. Any patients that are eligible for SRS (prospective cohort) or has already been treated with SRS (retrospective cohort) and also fulfil the eligibility criteria of the study will be invited to take part in the study. Patients will be recruited through the SRS clinics taking place at City Campus, Nottingham University Hospitals NHS Trust.
Key inclusion criteria (14 listed)
- Age: above 18 years, no upper limit
- Diagnosis of brain metastases or meningioma, where the treatment is going to be stereotactic radiosurgery
- Karnofsky Performance Status (KPS) ≥70
- Established diagnosis of cancer with absent or controllable primary disease
- Tumour volume of less than 20cc
Key exclusion criteria (6 listed)
- Previous RT to the brain, including SRS
- Previous surgery to the brain
- Not willing or not able to give informed consent
- Previous RT to the brain, excluding SRS
- Previous surgery to the brain
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurocognitive testingAlso: Montreal Cognitive AssessmentThe MoCA is a brief tool developed to screen mild cognitive impairment and has been validated in patients aged 55-85 years old. It has been tested and validated in patients with brain metastases, and its acceptability has been tested in the general brain tumour population. The paper version of the MoCA is available in nearly 100 languages. The online version is available currently in 5 languages. | Behavioural | Prospective, Retrospective |
| Quality of Life questionnaireAlso: QLQ-C30, QLQ-BN20The EORTC-QLQ-C30 is a quality-of-life questionnaire that was developed by the European Organisation for Research and Treatment of Cancer (EORTC) for use in clinical trials. It is a 30-item questionnaire that incorporates the following five scales: physical, role, cognitive, emotional and social. It has also been validated and is available in more than 100 languages. The EORTC-QLQ-BN20 is a questionnaire that was developed for use specifically with patients that have brain cancer. The BN20 is a 20-item questionnaire and addresses four different scales (multi-item): future uncertainty, visual disorder, motor dysfunction and communication deficit. There are seven items that assess physical symptoms: headaches, seizures, drowsiness, hair loss, itchy skin, weakness of legs and bladder control. The questionnaire has been validated in over 15 languages. The two questionnaires are meant to complement each other when used in patients with brain cancer. | Behavioural | Prospective, Retrospective |
| Stereotactic radiosurgeryAlso: SRSThis is a Standard of Care treatment for all the patients that will be recruited in both cohorts. Stereotactic radiosurgery will be delivered to one or more sites and in the prospective cohort can be delivered more than once. | Radiation | Prospective, Retrospective |
Primary outcome
Change from Baseline to neurocognitive function and Quality of Life at 6 months
Time frame: 6 months
Significant changes in neurocognitive function and Quality of Life at 6 months compared to baseline.The scale ranges from 0-100 with 0 signifying a worse quality of life and 100 signifying excellent quality of life for the participants. The cognitive function scale ranges from 0-30 with 30 signifying non-impaired cognitive function.
Doses related to neurocognitive symptoms
Time frame: 6 months
• Doses above which the lesion symptom mapping identifies areas of the brain relevant to neurocognitive symptoms at 6 months.
2 secondary outcomes
Recruitment feasibility
Time frame: 1.5 years
Patient reported symptoms vs symptoms identified by neurocognitive testing
Time frame: At baseline and every 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 28646895Lamba N, Muskens IS, DiRisio AC, Meijer L, Briceno V, Edrees H, Aslam B, Minhas S, Verhoeff JJC, Kleynen CE, Smith TR, Mekary RA, Broekman ML. Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis. Radiat Oncol. 2017 Jun 24;12(1):106. doi: 10.1186/s13014-017-0840-x.
- Background: PubMed 23810288Lippitz B, Lindquist C, Paddick I, Peterson D, O'Neill K, Beaney R. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treat Rev. 2014 Feb;40(1):48-59. doi: 10.1016/j.ctrv.2013.05.002. Epub 2013 Jun 27.
- Background: PubMed 12704393Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF. Voxel-based lesion-symptom mapping. Nat Neurosci. 2003 May;6(5):448-50. doi: 10.1038/nn1050. No abstract available.
- Background: PubMed 19285465Glascher J, Tranel D, Paul LK, Rudrauf D, Rorden C, Hornaday A, Grabowski T, Damasio H, Adolphs R. Lesion mapping of cognitive abilities linked to intelligence. Neuron. 2009 Mar 12;61(5):681-91. doi: 10.1016/j.neuron.2009.01.026.
- Background: PubMed 24179735Geva S, Baron JC, Jones PS, Price CJ, Warburton EA. A comparison of VLSM and VBM in a cohort of patients with post-stroke aphasia. Neuroimage Clin. 2012 Aug 30;1(1):37-47. doi: 10.1016/j.nicl.2012.08.003. eCollection 2012.
- Background: PubMed 20181476Taphoorn MJ, Claassens L, Aaronson NK, Coens C, Mauer M, Osoba D, Stupp R, Mirimanoff RO, van den Bent MJ, Bottomley A; EORTC Quality of Life Group, and Brain Cancer, NCIC and Radiotherapy Groups. An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients. Eur J Cancer. 2010 Apr;46(6):1033-40. doi: 10.1016/j.ejca.2010.01.012. Epub 2010 Feb 22.
- Background: PubMed 15817019Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.
- Background: PubMed 26900565Meyer S, Kessner SS, Cheng B, Bonstrup M, Schulz R, Hummel FC, De Bruyn N, Peeters A, Van Pesch V, Duprez T, Sunaert S, Schrooten M, Feys H, Gerloff C, Thomalla G, Thijs V, Verheyden G. Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits. Neuroimage Clin. 2015 Dec 11;10:257-66. doi: 10.1016/j.nicl.2015.12.005. eCollection 2016.
- Background: PubMed 29685411Renovanz M, Reitzug L, Messing L, Scheurich A, Gruninger S, Ringel F, Coburger J. Patient reported feasibility and acceptance of Montreal Cognitive Assessment (MoCA) screening pre- and postoperatively in brain tumour patients. J Clin Neurosci. 2018 Jul;53:79-84. doi: 10.1016/j.jocn.2018.04.034. Epub 2018 Apr 20.
- Background: PubMed 21520004Olson RA, Iverson GL, Carolan H, Parkinson M, Brooks BL, McKenzie M. Prospective comparison of two cognitive screening tests: diagnostic accuracy and correlation with community integration and quality of life. J Neurooncol. 2011 Nov;105(2):337-44. doi: 10.1007/s11060-011-0595-4. Epub 2011 Apr 26.
- Background: PubMed 18335256Olson RA, Chhanabhai T, McKenzie M. Feasibility study of the Montreal Cognitive Assessment (MoCA) in patients with brain metastases. Support Care Cancer. 2008 Nov;16(11):1273-8. doi: 10.1007/s00520-008-0431-3. Epub 2008 Mar 12.
- Background: PubMed 26425785Yang Y, Tompkins CA, Meigh KM, Prat CS. Voxel-Based Lesion Symptom Mapping of Coarse Coding and Suppression Deficits in Patients With Right Hemisphere Damage. Am J Speech Lang Pathol. 2015 Nov;24(4):S939-52. doi: 10.1044/2015_AJSLP-14-0149.
- NHS Website, MRI Scan MRI scan - NHS (www.nhs.uk) , page last visited on 12/02/2024Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul S Morgan, Professor of Medical Physics principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Metastases and Meningiomas, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline to neurocognitive function and Quality of Life at 6 months (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06466720, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.