Amino-acid PET Versus MRI Guided Re-irradiation in Patients With Recurrent Glioblastoma Multiforme - a Randomised Phase II Trial
The higher sensitivity and specificity of amino-acids (L-[methyl-11C]-methionine, MET and
O-(2-(1)-Fluoroethyl)-L-tyrosine, FET) positron emission tomography (AA-PET) in the
diagnosis of gliomas in comparison to computed tomography (CT) and magnetic resonance
imaging (MRI) was demonstrated in many studies and is the rationale for using them in target
volume delineation of these tumors. Several clinical trials have demonstrated the
significant differences between AA-PET and standard MRI in gross tumor volume (GTV)
delineation for treatment planning.
A small prospective study in patients with recurrent high grade gliomas treated with
stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival
when AA-PET or single photon emission tomography (AA-SPECT) were integrated in target volume
delineation, in comparison to patients treated using CT/MRI alone (Grosu et al. 2005).
However, there are no randomized studies demonstrating the impact of AA-PET based
irradiation treatment on the clinical follow-up in comparison to a traditional MRI/CT based
The goal of this study is to evaluate the impact of radiotherapy target volume delineation
based on AA-PET (new strategy) on the clinical outcome of patients with recurrent
glioblastoma (GBM) compared to target volume delineation based on contrast enhanced T1
weighted MRI (T1Gd-MRI) (traditional, established strategy). Concerning therapeutic safety,
the topography of recurrence outside the primary target volume as well as the localization
of necrosis after the re-irradiation will be determined. All side effects will be assessed
by CTCAE version 4.0 and the safety analyses will present the worst grade of acute and late
side effect by treatment arm for the whole study period (treatment and follow up). Patients
will be asked to complete a quality of life (QoL) questionnaire (as assessed by the E-ORTC
QLQ-C15 PAL) in regular time intervals.
This will be the first phase II randomized study evaluating the impact of molecular imaging
on outcome after radiotherapy in brain tumor patients.
Another goal of the technical part of this study is the development of a standardized
physical-technical methodology for the integration of AA-PET and other imaging biomarkers in
tumor volume delineation in radiation therapy.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression Free Survival (PFS)
6 months after randomization
Anca-Ligia Grosu, Prof. Dr. med.
Department of Radiotherapy, University Hospital Freiburg
Germany: Ethics Commission
AG NUK/RT 2010-1