To non-invasively measure metabolic alterations in GBM with 31P MRS at 7T and CEST MRI at 3T and 7T before and after radiotherapy (after the first session and after the whole treatment), and compare these results with Cx30 levels obtained from pre-…
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Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The study endpoint will be the amount of ATP, protein level and pH change in
GBM before and after single dose and complete course of radiotherapy with
respect to background levels. Reproducibility is assessed in controls assuming
no alteration in metabolite levels. In addition, the correlation between Cx30
and ATP as well as Cx30 and pH and protein level will be assessed.
Secondary outcome
NA
Background summary
Resistance to radiotherapy is a common problem in patients with glioblastoma
multiforme (GBM), one of the most common primary brain tumors in the adult
population. In this study, molecular information from tumor tissue, e.g. level
of Connexin30 (Cx30), will be used to predict radiotherapy efficacy and tumor
recurrence. Overexpression of Cx30 inhibits proliferation of tumor cells but
also renders them resistant to radiotherapy . Currently, there is no reliable
method to predict resistance to radiotherapy in a non-invasive way. To this
end, this study will be using non-invasive molecular profiling techniques at
ultra-high field 7T.
In stress situations, e.g. shear stress, hypotonia, and hypoxia, cells release
ATP (detectable non-invasively) into the extracellular space (ES). ATP
possesses anti-tumor activity and can regulate proliferation of cancer cells.
In addition, ATP can also act as a radio-protector. The similarity between Cx30
and ATP in the physiological effect exerted on the cells makes us hypothesize
that ATP as measured by 31P magnetic resonance spectroscopy (MRS) may be a
surrogate for Cx30, and therefore a marker of GBM resistance that can be
measured non-invasively. A second potential method to detect the physiological
response of tumor tissue to irradiation will be Chemical Exchange Saturation
Transfer (CEST) MR imaging. CEST MRI can probe tumor microenvironment, e.g. pH
and protein content with high spatial resolution and recently it has been shown
to be able to distinguish radiation necrosis from tumor recurrence. Changes in
tumor physiology in response to radiotherapy will translate to changes in pH
and/or protein content.
The primary aim of this study is to assess the feasibility of 31P magnetic
resonance spectroscopy (MRS) to quantify changes of ATP levels in brain tumors
in vivo before and after the first radiotherapy treatment. Our secondary aim is
to investigate the correlation between MRS-based ATP measurements and CEST
measurements before and after radiotherapy (after the first session and after
the whole treatment course) with Cx30 levels from the pre-treatment biopsy
samples measured by immunohistochemistry (IHC).
Study objective
To non-invasively measure metabolic alterations in GBM with 31P MRS at 7T and
CEST MRI at 3T and 7T before and after radiotherapy (after the first session
and after the whole treatment), and compare these results with Cx30 levels
obtained from pre-treatment biopsy.
Study design
The study is designed as a single-center pilot study. A total of 20 brain tumor
patients will be scanned with each patient being scanned three times (before
biopsy, immediate after the first radiation dose and immediately after the
whole radiotherapy treatment). In addition, a total of 20 healthy controls will
be scanned twice to to establish normal values.
Study burden and risks
The subjects participating in this study will not benefit from the results of
the study, since the primary aim of this investigation is to collect
feasibility data for a comparison between 31P MRS and CEST MRI and biopsy Cx30
values for patients treated for GBM. However, our ultimate aim is to use MRI to
predict radiotherapy response without the need for a biopsy. Three visits to
the 7T MRI facility will be required for each patient, before biopsy, after the
first radiotherapy dose and after the complete course of treatment. The healthy
volunteers will be scanned twice at 7T. The risk of undergoing MRI is low.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
Main inclusion criteria for patients and healthy volunteers:
• Minimum age 18 years
Additional inclusion criteria for patients:
• Recently diagnosed with GBM using biopsy
• Scheduled for radiotherapy (no surgical resection possible or desirable)
Exclusion criteria
Main exclusion criteria for patients and healthy volunteers:
• Standard contraindications for 7T MRI scanning, including claustrophobia and
active metallic implants (see standard 7T screening form for contraindications)
• History of previously treated brain tumor
• History of previous partial or total brain radiotherapy
• Pregnancy
Additional exclusion criteria for patients:
• Altered consciousness prohibiting informed consent
• Recurrent GBM
Design
Recruitment
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 | NL56019.041.17 |