Article
Surgical resection and intraoperative open photodynamic therapy of recurrent glioblastoma – a promising strategy for local tumour control
Resektion und intraoperative offene photodynamische Therapie bei rezidivierten Glioblastomen – eine vielversprechende Strategie zur lokalen Tumorkontrolle
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Authors
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Stephanie Schipmann-Miletic
- Universitätsklinik Münster, Klinik für Neurochirurgie, Münster, Deutschland
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Louise Stögbauer
- Universitätsklinik Münster, Klinik für Neurochirurgie, Münster, Deutschland
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Sebastian Zimmer
- Universitätsklinikum Münster, Institut für klinische Radiologie, Münster, Deutschland
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Nils Warneke
- Universitätsklinik Münster, Klinik für Neurochirurgie, Münster, Deutschland
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Benjamin Brokinkel
- Universitätsklinik Münster, Klinik für Neurochirurgie, Münster, Deutschland
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Oliver Grauer
- Universitätsklinikum Münster, Klinik für Neurologie, Münster, Deutschland
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Walter Stummer
- Universitätsklinik Münster, Klinik für Neurochirurgie, Münster, Deutschland
| Published: | May 8, 2019 |
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Outline
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Objective: Glioblastoma is a brain tumor with particular poor prognosis despite maximal multimodal treatment. Given the infiltrative nature of this tumor treatment options to improve local tumor control are urgently needed.
Fluorescence-guided resection with 5-aminolevulinic acid (5-ALA) is considered standard of care. Beside benefits to improve extent of resection, 5-ALA can be used as a photosensitizer for photodynamic therapy (PDT). PDT bases on a photochemical reaction activated by light, creating reactive oxygen species, leading to direct cytotoxic effects on tumor cells, destruction of vasculature, and induction of immune response. We present a method, that uses PDT, applied to the resection cavity after surgery of recurrent glioblastoma.
Methods: After 5-ALA guided resection of recurrent glioblastoma, laser diffusors are inserted into the resection cavity using neuronavigation. PDT is applied for 60 minutes (635 nm, 200 mW/cm diffusor, 1h). Cavities are continuously irrigated with ringer’s lactate to maintain clarity of optical media. The patient is ventilated with 100% oxygen during therapy. In addition to the routinely performed early postoperative MRI, further MRIs are performed after 14 days and 3 months. For MRI analysis, diffusion-tensor imaging (DTI) and T1+KM are used.
Results: Ten patients with recurrent glioblastoma have been treated with open PDT. No adverse event or new posttherapeutic neurological deficits have occurred. Early postoperative MRI revealed a cytotoxic edema along the margin of the resection cavity, appearing to be selective for remaining tumor, either from the infiltrating zone or non-resectable contrast-enhanced tumor. Follow-up MRI after 14 days demonstrated a posttherapeutic blood-brain-barrier breakdown with contrast-enhancement of the former region of the cytotoxic edema.
Conclusion: Open PDT provides a new method of further local tumor treatment. In some tumor cells fluorescence is not visible due to small concentrations of protoporphyrin IX. However, these cells are photosensitized as well and addressed by PDT. Additional open PDT to resection of macroscopic tumor enables creating a safety margin or treatment of non-resectable tumor in eloquent regions. Further prospective studies are warranted to evaluate the long-term effects regarding OS and PFS. In addition, the method might be eligible for first-line therapy as well. Immunological mechanisms triggered by this treatment strategy have to be evaluated.
