PMC

Tumor size was calculated by semi-automated contouring of tumor borders on each T1 weighted-slice (post gadolinium) in cm³, and additionally maximum 2D diameter in mm.

Sagittal MR T1-weighted images post gadolinium images of Patient No. 3 in whom the O₂-O₃ treatment was started following the initial surgery and diagnosis of (A) GB. Six months later, some contrast enhancement was still visible (B), that was not apparent four years following diagnosis (C).

Sagittal and transverse MR T1-weighted images post gadolinium images of Patient No. 1 (illustrative case) at diagnosis (A), at progression six months after the initial biopsy and standard radio-chemotherapy (B), and following tumor resection and implantation of the reservoir for the intra-tumoral O₂-O₃ treatment (C).

(A) The initial stereotactic biopsy showed a pleomorphic astrocytic tumor with focal necrosis (insert) corresponding to glioblastoma (WHO grade IV). (B) Also in the first recurrence (six months later) pleomorphic astrocytic tumor cells were present. Additionally, tumor vessels exhibited fibroid changes most likely as a therapy-induced alteration. (C) The first resection after application of O₂-O₃ showed CNS tissue with mainly reactive and resorptive changes. Note accumulation of macrophages (black arrowheads) that stain immunohistochemically for the CD68 (PGM1) antigen (insert). Only single scattered pleomorphic astrocytic (tumor) cells can be detected (white arrow). (D) Final resection about 3¼ years after the initial surgery presented with the histology of a full-blown cell-rich tumor recurrence. (E and F) HIF-2α staining at different time points: Note that there is markedly higher HIF-2α expression in the tissue from the first recurrence (prior to O₂-O₃) (E) than in the final resection immediately following O₂-O₃ treatment (F). HIF-2α is particularly expressed in blood vessels prior to O₂-O₃ (black arrowheads). No differences between biopsies were observed for HIF-1α immunostaining (data not shown). HIF, hypoxia-inducible factor.