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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
Open accessAbstract
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 cm 3 ). 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.
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“The use of ALA-PpIX as a fluorescent theranostic agent is well illustrated in a clinical trial where patients with recurrent glioblastoma underwent PpIX fluorescence-guided resection first followed immediately by PDT all after a single dose of ALA administration [165].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [165]
In the citing paper
“Selective ALA-induced PpIX disposition in tumors made it possible for maximum safe resection of glioblastoma as well as targeting infiltrating tumor cells and unresectable tumor tissues in eloquent regions by PDT, resulting in promising progression-free survival in a disease with dismal prognosis.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [165]
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Metadata
- Authors
- Schipmann, S., Müther, M., Stögbauer, L., Zimmer, S., Brokinkel, B., Holling, M., Grauer, O., Suero Molina, E., Warneke, N., & Stummer, W.
- Affiliations
- Department of Neurosurgery,
- Research Institute of Radiology (BY)
- University Hospital Münster (DE)
- Corresponding author
- Schipmann, Stephanie
- ORCID
- Venue
- Journal of Neurosurgery
- Published
- 2021-02
- Volume
- 134
- Issue
- 2
- Pages
- 426-436
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- OpenAlex
- W3001797168
- Cited by
- 121
- References
- 42
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 29 · 2023: 20 · 2022: 22 · 2021: 15
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of neurosurgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Westfälische Wilhelms-Universität Münster
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- recurrent glioblastoma, 5-aminolevulinic acid, fluorescence-guided resection, photodynamic therapy, porphyrins, local tumor control, cytotoxic edema, progression-free survival, high-grade glioma
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