Simulating photodynamic therapy for the treatment of glioblastoma using Monte Carlo radiative transport.

in Journal of biomedical optics by Louise Finlayson, Lewis McMillan, Szabolcs Suveges, Douglas Steele, Raluca Eftimie, Dumitru Trucu, Christian Thomas A Brown, Ewan Eadie, Kismet Hossain-Ibrahim, Kenneth Wood

TLDR

  • The study simulates a clinical trial that treats a rare and deadly form of brain tumor called Glioblastoma (GBM) with photodynamic therapy (PDT) via a laser coupled balloon device. The simulation uses a computational brain model containing a GBM to simulate light path and PDT effects. The study considers treatment parameters such as laser power, photosensitizer concentration, and irradiation time, as well as PDT's impact on brain tissue temperature. The simulation suggests that the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. The study's findings could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

Abstract

Glioblastoma (GBM) is a rare but deadly form of brain tumor with a low median survival rate of 14.6 months, due to its resistance to treatment. An independent simulation of the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial aiming to treat the GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device, is demonstrated. To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome. We use Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. Treatment parameters (laser power, photosensitizer concentration, and irradiation time) are considered, as well as PDT's impact on brain tissue temperature. The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence =at balloon wall) and assuming an initial photosensitizer concentration of. Increases in treatment time and light power (light fluence =at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the p hotosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration toand keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. To improve treatment outcome, focus should be placed on improving the photosensitizer. With further development and optimization, the simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM.

Overview

  • The study aims to simulate the INtraoperative photoDYnamic therapy for GliOblastoma (INDYGO) trial, a clinical trial that treats GBM resection cavity with photodynamic therapy (PDT) via a laser coupled balloon device. The simulation uses Monte Carlo radiative transport techniques within a computational brain model containing a GBM to simulate light path and PDT effects. The study considers treatment parameters such as laser power, photosensitizer concentration, and irradiation time, as well as PDT's impact on brain tissue temperature. The primary objective is to understand the PDT treatment parameters and their impact on the clinical outcome.

Comparative Analysis & Findings

  • The simulation suggests that 39% of post-resection GBM cells are killed at the end of treatment when using the standard INDYGO trial protocol (light fluence =at balloon wall) and assuming an initial photosensitizer concentration of. Increases in treatment time and light power (light fluence =at balloon wall) result in further cell kill but increase brain cell temperature, which potentially affects treatment safety. Increasing the photosensitizer concentration produces the most significant increase in cell kill, with 61% of GBM cells killed when doubling concentration toand keeping the treatment time and power the same. According to these simulations, the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature.

Implications and Future Directions

  • The study's findings suggest that the standard trial protocol is reasonably well optimized with improvements in cell kill difficult to achieve without potentially dangerous increases in temperature. The simulation could have potential clinical benefit and be used to help plan and optimize intraoperative PDT treatment for GBM. Future research should focus on improving the photosensitizer concentration and developing new PDT techniques to improve treatment outcomes while minimizing potential risks.
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