Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control

Stephanie Schipmann, Michael Müther, Louise Stögbauer, Sebastian Zimmer, Benjamin Brokinkel, Markus Holling, Oliver Grauer, Eric Suero Molina, Nils Warneke, Walter Stummer

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

OBJECTIVE High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.

METHODS After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.

RESULTS Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4–5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8–7.2 months).

CONCLUSIONS Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.
Original languageEnglish
Pages (from-to)426-436
Number of pages11
JournalJournal of Neurosurgery
Volume134
Issue number2
Early online date24 Jan 2020
DOIs
Publication statusPublished - 1 Feb 2021
Externally publishedYes

Keywords

  • protoporphyrin IX
  • 5-ALA
  • photosensitizing agents
  • photochemotherapy
  • photodynamic therapy
  • glioma
  • oncology

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