Rationale: Patients with IDH-wildtype glioblastoma or grade IV IDH-mutant astrocytoma
have a very poor prognosis despite standard treatment consisting of surgery,
radiotherapy, and chemotherapy. Diffuse infiltration of the brain by the tumor is thought
to be one of the main causes of this therapy-resistance. In order to improve the surgical
treatment, tumor regions with lower infiltration percentages need to be identified and
resected during surgery, a so-called supramarginal resection. Currently, pre-operative T1
contrast enhanced weighted (T1c) MRI is used to identify the tumor for resection. We
recently found the combination of apparent diffusion coefficient MRI and O-(2-[
18F]fluoroethyl-)-L-tyrosine positron emission tomography (ADC/FET) to be significantly
more accurate than T1c MRI alone in the detection of tumor infiltration. This makes
ADC/FET a suitable candidate to guide supramarginal resection. Since FET PET is not as
accessible and widely available as MRI, identification of an MRI based alternative could
result in a more widespread implementation. Amide proton transfer chemical exchange
saturation transfer (APT-CEST) MRI is a novel potential alternative for FET PET, since
both measures are related to protein content.
Objective: In this project we aim to develop a safe and effective technique for ADC/FET
guided resection of IDH-wildtype glioblastoma and grade IV IDH-mutant astrocytoma. The
safety concerns neurological deficits and time to start of adjuvant therapy, while the
effectiveness is aimed at the extent of resection. Our secondary aim is to evaluate the
diagnostic accuracy of APT-CEST MRI and to assess whether APT-CEST MRI can serve as an
alternative for FET PET for the detection of tumor infiltration.
Study design: prospective observational intervention study
Study population: 30 patients with clinical and radiological diagnosis of an untreated
high grade glioma (suspected for glioblastoma (IDH wildtype) or grade IV astrocytoma (IDH
mutant)), who are eligible for a supramarginal surgical resection and adjuvant treatment
according two neurosurgeons in consensus and who are in relatively good condition
(Karnofsky Performance Score (KPS) ≥70).
Intervention (if applicable): supramarginal ADC/FET-guided resection. To make sure that
the standard treatment is always guaranteed, T1c MRI abnormalities will be included in
the surgical target.
Main study parameters/endpoints: the main study endpoint is the optimization of
ADC/FET-guided resection. Volumetric and percentual extent of resection, as measured with
MRI and PET imaging, combined with surgery-induced morbidity will be used as outcome
parameters. The secondary study parameters will be the histopathology-based diagnostic
accuracy of APT-CEST MRI in comparison with FET PET, cognitive performance over time and
progression free survival.
Nature and extent of the burden and risks associated with participation, benefit and
group relatedness: participants will undergo pre- and postoperative MRI scanning. This is
also part of regular clinical care, except there are additional MRI sequences including
APT CEST in the pre-operative and pre-radiotherapy MRI. There are no risks associated
with MRI acquisition after MRI safety screening. Participants will furthermore undergo a
pre- and postoperative FET PET. The risks associated with PET scanning are limited, and
the radiation burden will remain below 10 mSv (ICRP62 category intermediate risk (level
IIb)). During surgery, biopsies are performed from areas that will be resected, so these
biopsies will not introduce any extra risk. A potential benefit is the possibility of the
removal of more tumor tissue. A potential risk is the additional removal of healthy brain
tissue with the risk of neurological damage, which is controlled by pre- and
intraoperative techniques such as visualization of white matter tracts and mapping (both
asleep and awake) of critical functions such as language and control of strength.