The main goal is to identify risk factors for radiation induced cognitive changes. Therefore, cerebral hemodynamic status of the patient, measured as cerebrovascular reactivity (CVR) with magnetic resonance imaging (MRI), at the start of radiation…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoints will be the change in neurocognitive test score between pre-
and post-radiotherapy in relation to cerebrovascular reactivity as measured
with MRI before the start of radiation treatment.
Secondary outcome
1. The changes in cerebral hemodynamics (CVR and cerebral blood perfusion) in
relation to the changes in cognitive performance 3 months after radiotherapy.
2. The spatial distribution of cerebral hemodynamics in relation to change in
cerebral hemodynamics 3 months after radiotherapy.
3. The spatial relationship between dose distribution and regional cerebral
hemodynamics changes 3 months after radiotherapy.
4. The spatial relationship between dose distribution and cerebral
morphological changes 3 months after radiotherapy.
5. Relation between patient reported QoL and performance on the NCA both before
and 3 and 11 months after radiotherapy.
6. Relation between changes in brain morphology (e.g. cortical thickness or
white matter tract integrity) and changes in cerebral hemodynamics and
cognitive performance.
7. Comparison of the WBRT and SRS group regarding cognitive performance and
cerebral hemodynamics.
8. Relation of compliance with both the CST and NCA in patients receiving
radiotherapy.
Background summary
Whole brain radiotherapy (WBRT) is a common therapy for the treatment of brain
metastases, or as prophylaxis to prevent intracranial metastases. An
alternative for the treatment of brain metastases is stereotactic radiosurgery
(SRS). The median overall survival time of patients with intracranial
metastases is approximately seven months with systemic and local treatment.
After brain irradiation patients may suffer from radiation induced brain injury
and neurocognitive deficits. Since cognitive functions are essential for our
daily social, occupational and personal life, impaired cognitive functioning
consequently affects quality of life (QoL) during the remaining life span of
these patients. It is currently not possible to predict the impact of
radiotherapy on individual patients. The pathogenesis of this radiation-induced
cognitive impairment is not fully understood, but some evidence suggests that
it could be considered a type of vascular dementia. The hypothesis is that
radiation damage to cerebral vessels leads to a reduced blood supply and
subsequent damage to brain tissue. Additionally, patients with impaired
vascularisation of the brain at start of radiotherapy have less reserve to
maintain the required blood supply. A reliable method to measure the
hemodynamic status of the cerebral vessels is cerebrovascular reactivity (CVR)
as measured during the cerebrovascular stress test (CST), which uses
respiratory challenges to estimate the reserve capacity of the microvasculature
of the brain. Our findings will work towards identifying risk factors for
radiation-induced cognitive changes. In the future this knowledge could be of
value in making treatment decisions.
Study objective
The main goal is to identify risk factors for radiation induced cognitive
changes. Therefore, cerebral hemodynamic status of the patient, measured as
cerebrovascular reactivity (CVR) with magnetic resonance imaging (MRI), at the
start of radiation therapy will be studied in relation to the change in
cognitive performance before and 3 and 11 months after radiotherapy. In
addition, changes in cerebral hemodynamics, radiation dose (spatial) response
relationship and patient compliance will be studied.
Study design
A prospective study.
Study burden and risks
Subjects will have no direct benefit from participating in this study. The NCA
has no risks. The only risk of this study is the chance of a transient increase
of the intracranial pressure during the hypercapnic stimulus. Therefore,
suspected increased intracranial pressure (defined as non-prophylactic >4 mg
dexamethasone use) is an exclusion criterion. Furthermore, an independent blood
oxygen saturation and respiratory rate monitoring will be performed during the
MRI measurements with fingertip pulse oximetry and a pressure sensor for the
respiratory rate. The controlled gas breathing will be administered using the
reliable RespirAct RA-MRTM MRI UNIT which has an open breathing system.
Subjects have to breathe through a mask. The increase in end-tidal CO2 (PetCO2)
we will apply will be within physiological ranges, experienced repeatedly
during a normal day and night and also occur spontaneously in patients with
gliomas while under (local) anaesthesia before resection. Nevertheless if
subjects do experience discomfort because of high arterial CO2 levels, the
operator can switch instantly to room air when the red button on the front of
the gas blender is activated. In the MRI, subjects can squeeze the panic
button.
Before participating in this research, all subjects will receive an extensive
explanation about the device and the procedure. We will administer the entire
respiratory protocol outside of the MRI scanner first, to see how the subject
reacts to the hypercapnic stimuli. Only when we are sure the subject is
comfortable with the respiratory challenges, we will perform the test in the
MRI. Subjects will be able to practice squeezing the MR panic button once
positioned on the scanner bed. The subjects will be able to withdraw themselves
at any moment throughout the study.
Additionally, the RespirAct RA-MRTM MRI UNIT that will be used to administer
the breathing challenges is a plug-and-play device and as such does not require
special training for operation. System failsafes, and the fact that subjects
are always open to room-air ensures that there is no possibility for accidental
hypoxia. Nonetheless all staff operating the RespirAct RA-MRTM MRI UNIT has
received official training by the manufacturer (Thornhill Research). Also, the
research group performing this research (including Dr. A. Bhogal) has extensive
experience with both the device and similar breathing protocols, thereby
ensuring maximum safety for participants.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
For patients:
- Age >= 18 years;
- Expected survival >= 5 months, as determined by Graded Prognostic Assessment
(GPA) score;
- Either radiographic and/or histologic proof of metastatic brain disease
eligible for cranial irradiation;
- Eligible for brain irradiation for prophylaxis or treatment;
- Signed informed consent;
- Sufficient knowledge of the Dutch language to allow reliable use of the
standardized tests and understand the study information;
- Participation in the COIMBRA cohort, with given consent for filling in QoL
questionnaires.
For healthy volunteers:
- Age >= 18 years;
- Signed informed consent;
- Sufficient knowledge of the Dutch language to understand the study
information.
Exclusion criteria
For patients and healthy volunteers:
- Unwilling or unable to cooperate with breathing manoeuvres or keeping still;
- Medical contraindications to limited hypercapnia (known metabolic acidosis or
alkalosis);
- Standard contraindications for 3T MRI scanning;
- Standard contraindications for using the RespirAct RA-MRTM MRI UNIT;
- Noncompliance with prescribed anti-seizure medication;
- Severe current neurological or psychiatric diseases (including pre-existent
dementia or other cognitive disorders as diagnosed by a neurologist,
psychiatrist or gerontologist), not related to the primary malignancy or
cerebral metastases;
- History of cerebrovascular disease (ischaemic stroke or intracranial
haemorrhage);
- Non-prophylactic use of >4 mg dexamethasone on the day of the
cerebrovascular stress test;
- Cardiovascular disease: congestive heart failure (New York Heart Association
Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled
by conventional intervention, and myocardial infarction within past 6 months as
diagnosed by a cardiologist;
- Pulmonary disease as diagnosed by a pulmonologist: oxygen dependency at rest
or with exercise, restrictive lung disease with resting respiratory rate over
15 breaths/min;
- Concurrent severe or uncontrolled medical disease (e.g., active systemic
infection);
- History of bleomycin treatment;
- Body weight <30 kg, >100 kg;
- Pregnancy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67227.041.18 |