Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review

Leroy, Henri‐Arthur; Guérin, Laura; Lecomte, F.; Baert, Gregory; Vignion, Anne-Sophie; Mordon, Serge; Reyns, Nicolas

doi:10.1016/j.pdpdt.2021.102492

Cited by 33 publications

(29 citation statements)

References 34 publications

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“…According to the literature, the use of only 5-ALA for FD and PDT is generally enough to increase the time of progression-free survival for glioblastoma up to 12-14.5 months, and in patients harboring high-grade gliomas, 13% become long-term survivors (>2 years) after PDT [24,25]. Our case showed achievement of gross total resection of the tumor under fluorescence monitoring according to MRI, but a poor result of PDT with 5-ALA mono use and additional therapy.…”

Section: Discussionmentioning

confidence: 99%

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results

et al. 2022

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The treatment of glial brain tumors is an unresolved problem in neurooncology, and all existing methods (tumor resection, chemotherapy, radiotherapy, radiosurgery, fluorescence diagnostics, photodynamic therapy, etc.) are directed toward increasing progression-free survival for patients. Fluorescence diagnostics and photodynamic therapy are promising methods for achieving gross total resection and additional treatment of residual parts of the tumor. However, sometimes the use of one photosensitizer for photodynamic therapy does not help, and the time until tumor relapse barely increases. This translational case report describes the preliminary results of the first combined use of 5-ALA and chlorin e6 photosensitizers for fluorescence-guided resection and photodynamic therapy of glioblastoma, which allowed us to perform total resection of tumor tissue according to magnetic resonance and computed tomography images, remove additional tissue with increased fluorescence intensity without neurophysiological consequences, and perform additional therapy. Two months after surgery, no recurrent tumor and no contrast uptake in the tumor bed were detected. Additionally, the patient had ischemic changes in the access zone and along the periphery and cystic-glial changes in the left parietal lobe.

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Section: Discussionmentioning

confidence: 99%

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results

et al. 2022

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“…To our knowledge, all human iPDT series have used a continuous illumination pattern [35,40]. We reported in previous preclinical studies the interest of light fractionation to let the target tissue reoxygenate between illumination periods [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use

Leroy¹,

Baert²,

Guérin³

et al. 2021

Cancers

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Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients harboring inoperable GBM, due to the anatomical location of the tumor or poor general condition of the patient, the life expectancy is even worse. The challenge of managing GBM is therefore to improve the local control especially for non-surgical patients. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment relying on the interaction of light, a photosensitizer and oxygen. In the case of brain tumors, iPDT consists of introducing one or several optical fibers in the tumor area, without large craniotomy, to illuminate the photosensitized tumor cells. It induces necrosis and/or apoptosis of the tumor cells, and it can destruct the tumor vasculature and produces an acute inflammatory response that attracts leukocytes. Interstitial PDT has already been applied in the treatment of brain tumors with very promising results. However, no standardized procedure has emerged from previous studies. Herein, we propose a standardized and reproducible workflow for the clinical application of iPDT to GBM. This workflow, which involves intraoperative imaging, a dedicated treatment planning system (TPS) and robotic assistance for the implantation of stereotactic optical fibers, represents a key step in the deployment of iPDT for the treatment of GBM. This end-to-end procedure has been validated on a phantom in real operating room conditions. The thorough description of a fully integrated iPDT workflow is an essential step forward to a clinical trial to evaluate iPDT in the treatment of GBM.

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“…PDT and its output are normally composed of a photosensitizer, light and oxygen species, and furthermore, photosensitizers are only activated in a specific wavelength of light and then produce reactive oxygen species (ROS) (i.e., PDT produces excessive ROS in the site of irradiation and then inhibits the viability of disease cells) [ 6 ]. Therefore, PDT has a toxic reaction only in the site of light irradiation, which means it is able to minimize any adverse effects against normal cells or tissues [ 3 , 4 , 7 , 8 ]. For example, Leroy et al reported that 5-aminolevulinic acid (5-ALA)-based PDT for brain cancer is efficient and safe for high-grade glioma [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PDT has a toxic reaction only in the site of light irradiation, which means it is able to minimize any adverse effects against normal cells or tissues [ 3 , 4 , 7 , 8 ]. For example, Leroy et al reported that 5-aminolevulinic acid (5-ALA)-based PDT for brain cancer is efficient and safe for high-grade glioma [ 8 ]. They argued that glioma patients receiving 5-ALA PDT recorded longer survival times than those without PDT.…”

Section: Introductionmentioning

confidence: 99%

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Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

Yang

Jeong

Kook

et al. 2022

IJMS

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Folic acid-conjugated nanophotosensitizers composed of folic acid (FA), poly(ethylene glycol) (PEG) and chlorin e6 (Ce6) tetramer were synthesized using diselenide linkages for reactive oxygen species (ROS)- and folate receptor-specific delivery of photosensitizers. Ce6 was conjugated with 3-[3-(2-carboxyethoxy)-2,2-bis(2-carboxyethoxymethyl)propoxy]propanoic acid (tetra acid, or TA) to make Ce6 tetramer via selenocystamine linkages (TA-sese-Ce6 conjugates). In the carboxylic acid end group of the TA-sese-Ce6 conjugates, FA-PEG was attached again using selenocystamine linkages to make FA-PEG/TA-sese-Ce6 conjugates (abbreviated as FAPEGtaCe6 conjugates). Nanophotosensitizers were fabricated by a dialysis procedure. In the morphological observations, they showed spherical shapes with small diameters of less than 200 nm. Stability of the aqueous FAPEGtaCe6 nanophotosensitizer solution was maintained (i.e., their particle sizes were not significantly changed until 7 days later). When H2O2 was added to the nanophotosensitizer solution, the particle size distribution was changed from a monomodal pattern to a multimodal pattern. In addition, the fluorescence intensity and Ce6 release rate from the nanophotosensitizers were also increased by the addition of H2O2. These results indicated that the nanophotosensitizers had ROS-sensitive properties. In an in vitro cell culture study, an FAPEGtaCe6 nanophotosensitizer treatment against cancer cells increased the Ce6 uptake ratio, ROS generation and light-irradiated cytotoxicity (phototoxicity) compared with Ce6 alone against various cancer cells. When the folic acid was pretreated to block the folate receptors of the Y79 cells and KB cells (folate receptor-overexpressing cells), the intracellular Ce6 uptake, ROS generation and thereby phototoxicity were decreased, while the MCF-7 cells did not significantly respond to blocking of the folate receptors. These results indicated that they could be delivered by a folate receptor-mediated pathway. Furthermore, an in vivo pulmonary metastasis model using Y79 cells showed folate receptor-specific delivery of FAPEGtaCe6 nanophotosensitizers. When folic acid was pre-administered, the fluorescence intensity of the lungs was significantly decreased, indicating that the FAPEGtaCe6 nanophotosensitizers had folate receptor specificity in vitro and in vivo. We suggest that FAPEGtaCe6 nanophotosensitizers are promising candidates for a targeted photodynamic therapy (PDT) approach against cancer cells.

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Is interstitial photodynamic therapy for brain tumors ready for clinical practice? A systematic review

Cited by 33 publications

References 34 publications

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results

The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results

Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

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