A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment

Abstract

Aim: Photodynamic therapy (PDT) appears to be a valuable new treatment modality for cancer therapy. Studies have reported successful application of PDT for glioblastoma. Here, we introduce a new device dedicated to intraoperative PDT delivered early after fluoro-guided resection combined with a transfer function that determines the treatment time based on the size of the surgical resection cavity. Materials & methods: First, we describe the device, which is composed of a trocar, a balloon filled with a diffusing solution, and a fiber guide in which a cylindrical light diffuser is inserted. Ex vivo experiments were performed to measure the fluence rate inside biological tissues. A calibration factor was defined to convert power measurements into fluence rate values. Calf brains were used to simulate light propagation in human brain tissue, and the photosensitizer administration effect on optical properties was discussed. The temperature elevation during illumination was evaluated. Results: Light power was measured in tissues surrounding the device during ex vivo experiments. Using the previously characterized calibration factor, power measurements were converted to fluence rate values to obtain the transfer function. No thermal elevation was observed during a 2-h temperature test, and the impact of protoporphyrin IX on brain optical properties was considered negligible. Conclusion: A discussion of experimental precision is presented. The light duration determined by the abacus had a standard deviation of <1 min. This value is weak compared with the total illumination time necessary to treat one patient. The main advantage of our device lies in its straightforward implementation of intraoperative PDT for neurosurgery with acceptable dosimetry and easy treatment time.

Age differences in photodynamic therapy‐mediated opening of the blood‐brain barrier through the optical clearing skull window in mice

“…In this work, another important approach for minimizing negative consequences of PDT effects to the brain vasculature and tissues is the application of the skull optical clearing technique [32,52,53]. Generally, PDT performance requires a craniotomy in both clinical and fundamental studies due to the high scattering property of the skull, which leads to low light penetration into the brain [7,9,10,[54][55][56]. However, the craniotomy leads to brain swelling, increasing in intracranial pressure and cortical inflammation [10].…”

Parallelized Monte-Carlo dosimetry using graphics processing units to model cylindrical diffusers used in photodynamic therapy: From implementation to validation

“…After assessing the Monte-Carlo algorithm in a homogeneous medium, evaluation in a more realistic environment was necessary. Thus, the Monte-Carlo model proposed here was used to confirm experimental ex-vivo measurements made by a specific device described in a previous study [43,44]. This device has been designed for intraoperative PDT treatment of brain tumors (see figure 3a) and is already being assessed in a phase I clinical study [45].…”

“…This factor is the combination of a calibration factor determined in air CF air and four other corrective coefficients. This methodology has also been described in a previous study [43].…”

INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial

“…Indeed, even if no fluorescence is observed after FGR, remaining tumor cells around and deeper in the cavity are still present and take up PpIX at a concentration, limiting their visualization through the microscope. These remaining cells that are not microscopically visible are the main target of the PDT treatment that is delivered by means of a new, recently designed lighting device 25 .…”

“…Discussion The main difficulty of this clinical trial relies on the use of a new medical device simultaneously with the evaluation of a drug repurposed for this condition. This issue was raised due to a comprehensive assessment of this new medical device 25 . Thus, once the safety of the medical laser system combined with the medical device was evaluated in a preclinical stage, a risk management procedure was delivered to an institutional review board for ethical consideration and to the French National Medicine Agency for legal consideration.…”