Abstract
Introduction
Glioblastoma (GB) is the most common primary malignant brain tumor in adults. The standard of care consists of maximal possible surgical resection with concomitant radiation therapy (RT) and temozolomide (TMZ). Currently the target volume delineation for RT is based on CT and MRI. In this study we investigated the feasibility of incorporating PET for guiding RT and the impact on treatment outcome by applying subvolume boosting to a [18F]-FAZA or [18F]-FET defined tumor part.
Methods
F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (CE-T1w) MRI. After tumor growth, a 30 min [18F]-FAZA (2h p.i.) or [18F]-FET (30min p.i.) PET was acquired. Subsequently, a treatment planning CT was obtained on the small animal radiation research platform (SARRP). After manual coregistration of CE-T1w-MRI, CT and PET images, a dose of 20 Gy was delivered to the target volume based on the CE-T1w-MRI (group 1–3). In group 2 and 3 an additional radiation boost of 5 Gy (1x1 mm) was delivered to the region with maximal PET probe uptake. On five consecutive days, TMZ (5 mg i.p.) was administered in groups 1–3. Group 4 was used as a sham group, receiving injections with saline. Tumor volumes on follow-up MRI were determined by drawing volumes of interest around the tumor on CE-T1w-MRI (PMOD).
Results
CE-T1w-MRI showed a heterogeneous tumor, enabling to select the MRI target volume. Both [18F]-FAZA and [18F]-FET exhibited an increased tumor uptake. Using three non-coplanar arcs, the dose delivered to the normal surrounding brain tissue was minimized. Significant differences in tumor volumes were found between the therapy and control groups (from day 2 onwards). No significant differences were observed between the different therapy groups (p-value range 0.082 - 1 for [18F]-FET; 0.327–1 for [18F]-FAZA PET).
Conclusions
Despite being very labor-intensive, MRI guided irradiation with PET subvolume boosting is feasible. Based on tumor growth, a significant difference was found between therapy and no therapy. Unfortunately, no significant difference could be observed between the treatment groups. Additional information from molecular imaging techniques enables the visualization of metabolically highly active regions. GB are highly heterogeneous solid tumors, hence the concept of biological target volume and multidimensional conformal RT seems promising.