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

Abstract

Significance: 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.

Aim: To develop a framework providing increased understanding for the PDT treatment, its parameters, and their impact on the clinical outcome.

Approach: 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.

Results: 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 = $200J/{\mathrm{cm}}^2$ at balloon wall) and assuming an initial photosensitizer concentration of $5\mu M$. Increases in treatment time and light power (light fluence = $400J/{\mathrm{cm}}^2$ 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 to $10\mu M$ and 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.

Conclusions: 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.

Keywords: Glioblastoma; Monte Carlo radiative transport; in silico; photodynamic therapy; photosensitizer protoporphyrin IX.