Computational Optimization of Irradiance and Fluence for Interstitial Photodynamic Therapy Treatment of Patients with Malignant Central Airway Obstruction

Abstract

There are no effective treatments for patients with extrinsic malignant central airway obstruction (MCAO). In a recent clinical study, we demonstrated that interstitial photodynamic therapy (I-PDT) is a safe and potentially effective treatment for patients with extrinsic MCAO. In previous preclinical studies, we reported that a minimum light irradiance and fluence should be maintained within a significant volume of the target tumor to obtain an effective PDT response. In this paper, we present a computational approach to personalized treatment planning of light delivery in I-PDT that simultaneously optimizes the delivered irradiance and fluence using finite element method (FEM) solvers of either Comsol Multiphysics® or Dosie™ for light propagation. The FEM simulations were validated with light dosimetry measurements in a solid phantom with tissue-like optical properties. The agreement between the treatment plans generated by two FEMs was tested using typical imaging data from four patients with extrinsic MCAO treated with I-PDT. The concordance correlation coefficient (CCC) and its 95% confidence interval (95% CI) were used to test the agreement between the simulation results and measurements, and between the two FEMs treatment plans. Dosie with CCC = 0.994 (95% CI, 0.953–0.996) and Comsol with CCC = 0.999 (95% CI, 0.985–0.999) showed excellent agreement with light measurements in the phantom. The CCC analysis showed very good agreement between Comsol and Dosie treatment plans for irradiance (95% CI, CCC: 0.996–0.999) and fluence (95% CI, CCC: 0.916–0.987) in using patients’ data. In previous preclinical work, we demonstrated that effective I-PDT is associated with a computed light dose of ≥45 J/cm2 when the irradiance is ≥8.6 mW/cm2 (i.e., the effective rate-based light dose). In this paper, we show how to use Comsol and Dosie packages to optimize rate-based light dose, and we present Dosie’s newly developed domination sub-maps method to improve the planning of the delivery of the effective rate-based light dose. We conclude that image-based treatment planning using Comsol or Dosie FEM-solvers is a valid approach to guide the light dosimetry in I-PDT of patients with MCAO.

Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends

“…The results demonstrated that The outcomes of finite element modeling were validated by the findings of experimental light dosimetry in a solid phantom with optical properties corresponding to those of biotissues. The correlation coefficient between the simulation results in the Comsol and Dosie packages and the clinical imaging results of four patients with malignant central airway obstruction demonstrated a high degree of agreement in terms of radiation fluence rate and fluence [107].…”

“…This approach simultaneously optimized fluence rate and fluence. This was achieved using the finite element method of Comsol Multiphysics 6.2 or the Dosie 0.0.3 software to study light propagation in biotissue (Figure 11) [107]. The Monte Carlo method was employed to simulate the propagation of excitation photons and PpIX fluorescence photons in a three-dimensional model of normal skin tissue, including a tumor containing PS, i.e., PpIX, with the corresponding optical properties of normal and tumor tissue.…”