Stereotactic interstitial photodynamic therapy using 5 aminolevulinic acid is a more upcoming approach for the treatment of malignant gliomas, whose treatment is remaining a major challenge in brain tumor therapy. The therapeutic outcome of 16 patients who underwent 5-ALA iPDT for newly diagnosed glioblastomas, are presented. In addition to the basic survival analysis, MRI data was analyzed concerning image changes after iPDT and the possibility to use these changes as prognostic factor for therapy response. Overall the iPDT showed a progression-free survival (PFS) of 16.4 months and an overall survival (OS) of 28.0 months. A PFS longer than 2-years was seen for 43.8% of iPDT patients. In contrast to this complete tumor resection with consecutive chemoradiation shows 8.9% 2-year PFS. Standard MRI-related prognostic factors of the tumor resection like necrosis-tumor ratio, tumor volume and post-treatment contrast enhancement are not useful for iPDT prognosis. This shows that the MRI interpretation has to be different compared to conventional tumor therapy. The survival results showed that iPDT is a potential treatment option especially for tumors, where standard therapy is not possible. Further studies are needed.
5-aminolevulinic acid (5-ALA) mediated interstitial photodynamic therapy (iPDT) is undergoing clinical trials for the treatment of malignant gliomas. 5-ALA iPDT is based on the creation of reactive oxygen species (ROS) via excitation of 5-ALA mediated protoporphyrin IX (PpIX) in the tumor cells and causing a phototoxic reaction. After iPDT local chemo-radiation is performed as adjuvant therapy. 16 newly diagnosed glioblastomas and 44 malignant glioma recurrences treated with 5-ALA iPDT in Munich were retrospectively analyzed for treatment outcome, spectral online monitoring and changes in the MRI. iPDT for newly diagnosed glioblastomas showed a median overall survival (OS) of 28 months, 16.4 months progression free survival (PFS), respectively. 43.8% patients with newly diagnosed glioblastoma experienced a long term PFS > 24 months. In addition, the methylation of the MGMT promotor showed to be a prognostic factor for prolonged survival (p=0.04). In case of recurrent malignant gliomas PFS after iPDT was 7.1 months with 25% >24 months survival after iPDT (17.9% PFS > 24 months). Analysis of spectral online monitoring showed that a measured decrease of the laser light transmission between the cylindrical diffuser fibers, used for the irradiation, can be associated with silent hemorrhages visible in terms of T1-hyperintensity in the MRI after iPDT. Overall 5-ALA iPDT is a promising tool for the treatment of glioblastomas and other malignant gliomas with prolonged survival and minimally invasive surgery.
KEYWORDS: Magnetic resonance imaging, Absorption, Signal detection, Tumors, Photodynamic therapy, Tissue optics, Luminescence, In vitro testing, Diffusion, Data acquisition
Losses in treatment light transmission during interstitial PDT were found to correlate with T1 hyperintensity in post-therapeutic non-contrast-enhanced T1-weighted MRI. This finding might be related to iPDT-induced early formation of methemoglobin.
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