ALA and Malignant Glioma: Fluorescence-Guided Resection and Photodynamic Treatment

Background: Oral application of 20 mg/kg body weight of 5-aminolevulinic acid (ALA) leads to a highly specific accumulation of fluorescent Protoporphyrin IX (PPIX) in malignant glioma tissue. In the past few years, we have participated in several clinical studies designed to investigate fluorescence guided resection (FGR) and photodynamic therapy (PDT). Methods: PPIX selectivity and PPIX bleaching during PDT were assessed with spectroscopic measurements. FGR was performed in 18 clinics in Germany (ALA-Glioma Study Group, participants see end of paper) in a phase III trial comprising an ALA group and a white-light group. PDT was performed with microlens fibers or cylindrical diffusers postsurgically to the resection bed. Additionally, a protocol for the interstitial stereotactic placement of cylindrical diffusers was established and applied on patients with recurrent, inoperable glioblastoma. Results: Compared to normal cortex, mean PPIX fluorescence in vital tumor was found more than 100-fold increased. During PDT, the PPIX fluorescence bleached to 8%, 16%, and 1% of the initial intensity for the 100, 150, and 200 J/cm2 groups (median values). FGR: Contrast-enhancing tumor was completely resected in 65% of patients in the ALA group compared to 36% in the white-light group (p < 0.0001). Progression-free survival was superior in the ALA group compared to white-light patients with cumulative 6 months progression-free survival rates of 41% and 21% (p = 0.0003), respectively. Interstitial PDT can be performed with multiple radial diffusers approximately 10 mm apart, 200 mW/cm, and an irradiation time of one hour.