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

Abstract

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.

Photodynamic therapy for malignant brain tumors in children and young adolescents

“…This will allow visual confirmation of the position and laser irradiation with pinpoint accuracy, even in areas where the brain parenchyma covers and obscures the resection cavity. In addition, as described previously, a new methodological concept of interstitial PDT was recently introduced, and the development of methods or devices for more effective PD irradiation is expected to continue in the future ( 16 , 17 ). The third unresolved issue is that PDT irradiation takes additional time; one shot of PDT takes 3 min.…”

“…Conversely, the disadvantage of PDT, particularly that utilized in the present study, is that the depth of the light is limited to 2.0 to 4.0 mm; therefore, maximum surgical resection is mandatory to achieve optimal effects ( 6 , 10 , 13 ). Recently, the methodological concept of interstitial PDT was introduced, and it is expected that various new methods will be developed to enable the delivery of the PD laser to the target location with equal or better efficacy in the future ( 16 , 17 ). This will also allow the expansion of the indications of PDT treatment for children and young adolescents, a new age group.…”

Bibliometric Analysis of Global Research on Cancer Photodynamic Therapy: Focus on Nano-Related Research

“…As shown in Figure 7A , all of them could be classified into four categories. We could find that current research directions for CPDT mainly focus on studies on nanomaterial technology ( Eisenbrey et al, 2018 ; Hu et al, 2019 ; Xavierselvan et al, 2021 ), clinical applications ( Leroy et al, 2021 ; Yano et al, 2021 ), mechanism ( Juarranz et al, 2008 ; Robertson et al, 2009 ), and photosensitizers ( Zhang, et al, 2018 ). Besides that, in the overlay visualization map of keywords co-occurrence analysis, VOSviewer could impart keywords with different colors according to their AAY.…”

Exploring Monocytes-Macrophages in Immune Microenvironment of Glioblastoma for the Design of Novel Therapeutic Strategies

“…When glioma cells absorb a molecule called photosensitizer (PS), exposure to high intensity laser light will be able to kill tumor cells by light activable reactive oxygen species (ROS) reactions in the photodynamic therapy (PDT) [ 113 , 114 ]. Clinical trials with classical PS have been conducted in a few countries such as Australia, France, and Japan, where results in newly diagnosed HGG patients indicate greater success (NCT01966809, NCT01148966, NCT04391062, JMA-IIA00026) [ 115 , 116 ]. PDT approach not only involves direct tumor cell destruction, but also the mechanisms of ROS-mediated activation can promote other antitumoral effects such as the activation of immune response [ 117 ], a vascular supply reduction [ 118 ], and also the opening of the BBB to enhance drug permeability into brain tissue [ 111 ].…”