Impact of Reirradiation Utilizing Fractionated Stereotactic Radiotherapy for Recurrent Glioblastoma.

BACKGROUND: Patients with recurrent glioblastoma (GBM) have limited treatment options. This study determined whether patients with recurrent GBM treated with initial radiation/temozolomide (TMZ) and reirradiation using fractionated stereotactic radiotherapy (FSRT) had improved outcomes. MATERIALS AND METHODS: We identified 95 patients with recurrent GBM, 50 of whom underwent FSRT at recurrence and 45 who had systemic treatment only (control). The median total FSRT dose at the time of GBM recurrence was 30 Gy in five fractions of the gadolinium-enhanced tumor only. RESULTS: With a median follow-up of 18 months, the progression-free survival (PFS) and overall survival (OS) following initial GBM diagnosis were longer in the reirradiation group compared to the control group (13.5 vs. 7.5 months [p=0.001] and 24.6 vs. 12.6 months [p<0.001], respectively). For patients who underwent reirradiation, the median time interval between the end of the initial radiation and reirradiation was 15.2 months. The median OS after GBM recurrence was longer in the reirradiation group versus the control group (9.9 vs. 3.5 months [p<0.001]), with a one-year OS survival rate of 22%. The hazard ratio for death of patients in the reirradiation group was 0.31 [0.19-0.50]. The reirradiation group had a higher percentage of patients who received bevacizumab (BEV, 62.0% vs. 28.9%, p=0.002) and a lower percentage of patients whose TMZ was discontinued due to toxicity (8.0% vs. 28.9%, p=0.017) compared to the control group. CONCLUSIONS: Reirradiation utilizing FSRT was associated with improved PFS and OS after GBM recurrence compared to the control group who did not receive additional irradiation.

Assessing cellulose microfibrillar structure changes due to cellulase action.

There is a need to understand how cellulose structural properties impact productive cellulase-cellulose interactions toward solving the mechanisms of the heterogeneous reaction. We coupled biochemical studies of cellulose hydrolysis by a purified Trichoderma reesei Cel7A (TrCel7A) cellobiohydrolase with atomic force microscopy (AFM) to study the impact of the cellulolytic activity on the fibrillar structure of cellulose. Bacterial cellulose (BC) fibrils were hydrolyzed by TrCel7A then immobilized by hydrophobic interactions on glass for AFM imaging. Commonly used methods to culture and isolate cellulose fibrils resulted in significant oxidation of the reducing-ends but minimal oxidation along the fibrils. We observed extensive fibrillation of BC fibrils to ∼3 nm microfibrils during the course of hydrolysis by TrCel7A, leaving thinned un-fibrillated recalcitrant fibrils at >80% hydrolysis extents. Additionally, this remaining fraction appeared to be segmented along the fibril length.