Pilot Study on the Determination of Therapy Resistant Areas Within the Tumor in Patients With High-Grade Glioma by Repeated 18F-FDG-PET-CT Scans
Patients harboring a primary intracerebral high grade tumor (WHO III- IV) have a median
survival of six to 12 months. Combined chemoradiotherapy with temozolomide is now the
standard of care since results of the joint EORTC-NCIC phase III study randomizing between
radiotherapy alone and combined radiochemotherapy with temozolomide showed a significant
improvement in 2-years survival from 8% to 24% for the combined treatment arm (Stupp 2005).
A differentiation between possible responders and non-responders before the start of
irradiation may eventual be possible by the use of 18F-FDG PET-CT. Preliminary own results
have shown that a higher metabolic activity in glioblastoma as measured on a simulation
18F-FDG PET-CT scan can be a prognosticator for shortened survival (Baumert, 2006).
Our preliminary data show that a high uptake of 18F-FDG on a PET-CT scan before radiotherapy
in glioblastoma could be a marker for reduced survival.
Popperl et al showed that dual phase FDG PET imaging is superior in differentiating
low-grade from high-grade recurrent astrocytomas (Popperl, 2006). Visual analysis of
delineation of glioma showed that the delayed images (imaged first 0-90 min and once or
twice later at 180-480 min after injection) better distinguished the high uptake in tumors
relative to uptake in gray matter. SUV comparisons also showed greater uptake in the tumors
than in gray matter, brain, or white matter at the delayed times (Spence et al).
These findings support the view that by using FDG-PET scans we could image active areas
within the tumor. Indeed, in vivo, a cancer is made up by different types of cells,
including hypoxic cells, cells that proliferate more fast, as well as by non-malignant
tissues, including inflammatory cells and vasculature.
Intra-tumor heterogeneity in malignant glioma is often observed and can be visualised also
by current PET-CT techniques.
The dynamics of the tracer uptake in the different tumor sub-volumes may give important
information about the biological characteristics as well. Indeed, the dynamics of FDG uptake
per cell are dependent on the blood flow, the uptake in the cell and the phosphorylation.
All these of these steps give information on the biology of the cancer in that particular
area of the tumor.
Observational Model: Case-Only, Time Perspective: Prospective
To determine the localisation within the primary tumour of the therapy resistant cells, before and during radiotherapy to determine the accurate boost volume. To determine changes during treatment intra- and extratumoral within the irradiated area.
after acquisition of all planned PET CTs
Brigitta Baumert, MD PhD
Maastricht Radiation Oncology
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)