Multimodal image-guided resection of IDH-wildtype glioblastoma and grade IV IDH-mutant astrocytoma

Patients with IDH-wildtype glioblastoma or gade 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.

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.

Prospective observational intervention study

Supramarginal resection will be guided by ADC/FET. To make sure that the
standard treatment is always guaranteed, T1c MRI abnormalities will be included
in the surgical target.

Participants will undergo a pre- and postoperative MRI. This is also part of
regular clinical care, except there are additional MRI sequences in the
preoperative MRI including APT-CEST. 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.