Glioblastoma imaging for the detection of tumor progression using amide proton transfer weighted chemical exchange saturation transfer MRI

A major issue with glioblastoma treatment is the occurrence of contrast
enhancement after treatment with radiotherapy or chemoradiotherapy. This
enhancement can be due to more tumor growth; called true progression. It can
also be due to treatment-related effects; called pseudoprogression. Amide
proton transfer weighted (APTw) chemical exchange saturation transfer (CEST)
magnetic resonance imaging (MRI) is a technique that indirectly images
pro-teins and peptides in a tissue. Because these molecules are overexpressed
in tumor tissue, APTw-CEST MRI has been shown to be good at distinguishing
between true progression and pseudoprogression, which is important as they
require vastly different responses.

This technique shows promise to become an important biomarker in glioblastoma
treatment, how-ever it currently lacks standardization, as studies are
generally done in one center on MRI machines of one vendor.

This multi-center study will make APTw-CEST MRI a clinically usable biomarker
for the de-tection of tumor progression in glioblastoma patients by providing
acquisition and post-pro-cessing recommendations, as well as a threshold on
APTw-CEST images that would allow a
clinician to accurately distinguish between pseudoprogression and true
progression, regard-less of where the images were acquired and with which
system.

The underlying processes that make APTw-CEST a reliable biomarker for
glioblastoma treat-ment response evaluation are not clearly known. Using other
advanced MRI techniques (dif-fusion, perfusion) and
O-(2-[18F]fluoroethyl-)-L-tyrosine Positron Emission Tomography
(FET-PET), and correlating these images with the APTw-CEST images will give a
better in-sight into these processes.

Primary Objective:
Determine the optimal threshold on APTw-CEST images in a multi-center (4
academic insti-tutes) multi-vendor (Philips, Siemens and GE) clinical trial, to
distinguish tumor progression from treatment-related effects.

Secondary Objective(s):
* Correlate APTw-CEST MRI to complimentary, advanced imaging parameters such as
FET-PET, diffusion and perfusion MRI, and Response Assessment for
Neuro-Oncol-ogy (RANO) criteria.
* Provide recommendations for the acquisition and post-processing of APTw-CEST
MRI.

In this prospective cohort study, all clinical MRI scans will be extended with
the APTw-CEST protocol. The patient receives their standard care and decisions
will be made based on standard-of-care imaging.

The APTw-CEST images and diagnosis from standard follow-up will be used to
determine the threshold on APTw-CEST images that would most accurately
distinguish between pseudoprogression and true progression early after
treatment.

Additional advanced imaging (diffusion, perfusion, FET-PET) taken during the
treatment and follow-up of the patient will be used to correlate areas of high
APTw signal with other signals.

:The clinical care of the patient group will not be altered. The APTw-CEST
images will not be used to make any clinical decision. Patients will not have
personal benefit from this study, and will have the burden of a prolonged scan
time of 10-15 minutes.

All further imaging used in this study; perfusion, diffusion and FET-PET will
not be taken specifically for this study and will only be taken when clinically
indicated, except in LUMC where the FET-PET will be added to standard-of-care.

The addition of FET-PET in the patient group in LUMC is warranted as the
long-term risks are negligible for this patient
group, due to the median survival of 12-14 months.