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

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 = 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.

Depth Penetration of Light into Skin as a Function of Wavelength from 200 to 1000 nm.

An increase in the use of light-based technology and medical devices has created a demand for informative and accessible data showing the depth that light penetrates into skin and how this varies with wavelength. These data would be particularly beneficial in many areas of medical research and would support the use and development of disease-targeted light-based therapies for specific skin diseases, based on increased understanding of wavelength-dependency of cutaneous penetration effects. We have used Monte Carlo radiative transport (MCRT) to simulate light propagation through a multi-layered skin model for the wavelength range of 200-1000 nm. We further adapted the simulation to compare the effect of direct and diffuse light sources, varying incident angles and stratum corneum thickness. The lateral spread of light in skin was also investigated. As anticipated, we found that the penetration depth of light into skin varies with wavelength in accordance with the optical properties of skin. Penetration depth of ultraviolet radiation was also increased when the stratum corneum was thinner. These observations enhance understanding of the wavelength-dependency and characteristics of light penetration of skin, which has potential for clinical impact regarding optimizing light-based diagnostic and therapeutic approaches for skin disease.

Computer Modeling Indicates Dramatically Less DNA Damage from Far-UVC Krypton Chloride Lamps (222 nm) than from Sunlight Exposure.

This study aims to investigate, with computer modeling, the DNA damage (assessed by cyclobutane pyrimidine dimer (CPD) formation) from far-ultraviolet C (far-UVC) in comparison with sunlight exposure in both a temperate (Harwell, England) and Mediterranean (Thessaloniki, Greece) climate. The research utilizes the published results from Barnard et al. [Barnard, I.R.M (2020) Photodermatol. Photoimmunol. Photomed. 36, 476-477] to determine the relative CPD yield of unfiltered and filtered far-UVC and sunlight exposure. Under current American Conference of Governmental Industrial Hygienists (ACGIH) exposure limits, 10 min of sunlight at an ultraviolet (UV) Index of 4-typical throughout the day in a temperate climate from Spring to Autumn-produces equivalent numbers of CPD as 700 h of unfiltered far-UVC or more than 30 000 h of filtered far-UVC at the basal layer. At the top of the epidermis, these values are reduced to 30 and 300 h, respectively. In terms of DNA damage induction, as assessed by CPD formation, the risk from sunlight exposure greatly exceeds the risk from far-UVC. However, the photochemistry that will occur in the stratum corneum from absorption of the vast majority of the high-energy far-UVC photons is unknown, as are the consequences.