Trial Information

Observational Study of Impact of [11C]-Methionine PET/MRI as a Tool for Individual Tailoring Postoperative Radiochemotherapy for Patients With Glioblastoma Multiforme

The current study aims to investigate the association of high [11C]MET tracer uptake before
postoperative radiochemotherapy and concurrent temozolomide (TMZ) with time to recurrence in
patients with glioblastoma multiforme (GBM).

[11C]MET-PET is expected to provide diagnostic (quantitative and spatial information) as
well as prognostic information, to monitor treatment, to help stratification of patients for
radiotherapeutic interventions such as dose-painting in order to optimize clinical
applications and potentially improve the treatment outcome.

This study aims to provide the basis (e.g. optimal threshold value, sensitivity, specificity
of MET uptake) for later intervention trials for treatment intensification, e.g. proton
boost irradiation based on specific biomarkers.

The trial is a one-arm single-center, non-randomized observational (biomarker) study. After
resection or biopsy, patients with newly diagnosed glioblastoma multiforme will receive a
[11C]MET-PET/MRI scan before start of concurrent radiochemotherapy (~1-4 weeks after
surgery). A fusion with the planning CT for irradiation treatment planning will be
performed. Postoperative radiotherapy will be applied in daily fractions of 2 Gy given 5
days per week for 6 weeks, for a total dose of 60 Gy (50 Gy and a boost of 10 Gy), with
concomitant administration of daily Temozolomide (75 mg/m2 p.o.) from the 1st day to the
last day of radiotherapy. Follow up with [11C]MET-PET/MRI will be performed every 3 months
until recurrence or until death of the patient.

The uptake of [11C]MET-PET (as standard uptake value - SUV) in tumour and in normal
contralateral grey matter before start of concurrent radiochemotherapy will be determined.
For each tumour, the ratio between tracer uptake in the tumor and contralateral gray matter
will be calculated (lesion-to-gray matter ratio [l/g]).

Primary end point will be time to recurrence (TTR) as function of [11C]MET uptake before
chemoradiotherapy. Secondary endpoints will be overall survival; toxicity; C-Index/ROC curve
(sensitivity, specificity, optimal threshold for normal/tumour tissue index), necrosis rate;
site of recurrence.

The primary analysis will use the Cox proportional hazard model to establish the linear
association between [11C]-MET and time-to-recurrence using a one-sided alpha = 0.1.

Parallel translational studies with orthotopic GBM xenografts (generated from the patients
material in the trial) in nude mice will be performed in our laboratory to evaluate
[11C]MET-PET as a tool for tailoring high precision radiotherapy. Histological, biological
and genetic studies are planned to validate the imaging finding and to explore the
underlying mechanisms.