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

Louise Ann Finlayson, Lewis Thomas McMillan, Szabolcs Suveges, Douglas Steele, Raluca Eftimie, Dumitru Trucu, C Tom A Brown, Ewan Eadie, Kismet Hossain-Ibrahim, Kenny Wood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 photo- dynamic 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 = 200 J∕cm2 at balloon wall) and assuming an initial photosensitizer concentration of 5 μM. Increases in treatment time and light power (light fluence = 400 J∕cm2 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 μM 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.
Original languageEnglish
Article number025001
Number of pages24
JournalJournal of Biomedical Optics
Volume29
Issue number2
DOIs
Publication statusPublished - 6 Feb 2024

Keywords

  • Glioblastoma
  • Photodynamic therapy
  • Photosensitizer protoporphyrin IX
  • Monte Carlo radiative transport
  • In silico

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