gms | German Medical Science

Objective: Pseudoprogression (PP) is an important clinical problem after radiation therapy of glioblastoma (GBM). From neuroradiological perspective, PP is defined as a new or enlarging contrast enhancement, in the absence of tumor growth. This condition subsides or stabilizes without a change in the therapy. Clinical definitions for PP are not standardized. This explains the variability in the published rates of PP with 10 to 31% after photon therapy in the first-line therapy of GBM. There is concern for higher rates of PP after proton therapy. The purpose of this study was to evaluate early magnetic resonance imaging (MRI) changes, PP, and local blood circulation after proton therapy for GBM.

Methods: Serial MRI scans of 26 patients with GBM were reviewed. Progressive disease (PD) was defined by the RANO criteria for radiographic response assessment in GBM. Cerebral blood flow (CBF) and cerebral blood volume (CBV) in the tumor area were analyzed by perfusion MRI with dynamic susceptibility contrast (DSC) technique. All patients were treated with initial tumor resection followed by combined chemo- and radiation therapy. Radiation therapy were performed in all cases with 50.0?Gy photons followed by a proton boost with 10?Gy equivalent (Gy(RBE)).

Results: MRI scans at 4 weeks after the end of radiation therapy and at 3 months were available in all patients. Perfusion MRI for the evaluation of CBF and CBV was performed in 18 patients (69.2%). Increase in contrast enhancement and progress in T2 FLAIR hyperintensity at 4 weeks and at 3 months after the end of radiation therapy were observed in 65% (N=17/26) and 34.6% (N=9/26), respectively. A PD at 4 weeks by RANO criteria was observed in 53.8% (N=14/26 of the cases. PP was observed in 57.1% of the cases with a PD at 4 weeks (N=8/14). The cumulative incidence of PP was 30.8% (N=8/26) at 3 months. DSC imaging at 4 weeks showed an absence of increased CBF and CBV at the former tumor area in 87.5% (N=7/8) of the patients with PP compared to only 16.7% (N=1/6) of the patients with PD (P=0.008). A sensitivity of 87.5% and a specificity of 83.3% for the prediction of PP by DSC imaging were calculated.

Conclusion: Early changes in MRI after proton boost therapy are common. By the RANO criteria PP rates are in the range of patients after photon therapy. MRI with DSC is very sensitive in the prediction of PP and could be helpful for early detection of PP after proton therapy.