Prediction of the photodynamic therapy effect using digital breast phantoms from patients with breast cancer via Monte Carlo simulations.

Significance: Photodynamic therapy (PDT) agents activated by near-infrared (NIR) light have demonstrated effectiveness in animal studies. However, clinical trials in humans are lacking due to biocompatibility concerns. We evaluate the feasibility of NIR-PDT using newly developed upconversion nanoparticles-quantum dots-Rose Bengal (UCQRs) through Monte Carlo simulations.

Aim: Surgery, the primary treatment mode for breast cancer, often reduces the quality of life due to scarring, necessitating a less invasive alternative. Herein, we propose an NIR-PDT approach using UCQRs to treat patients with early-stage breast cancer. The treatment can be performed on patients in the prone position using light irradiation alone, significantly reducing the burden on patients. In NIR-PDT using UCQR, a treatment depth of 3 to 4 cm can be expected based on the penetration depth of the 808-nm excitation light.

Approach: We created 150 digital breast phantoms by reconstructing breast slice images from breast computed tomography scans. These phantoms were classified by breast density and tumor depth, and simulations were performed on representative models. The therapeutic effect of NIR-PDT was assessed based on the amount of singlet oxygen generated, calculated from the fluence in the tumor voxels.

Results: The simulations indicated that tumor depth had a greater impact on the therapeutic outcomes compared with breast contour or structure. In all phantoms where tumors with a 7-mm diameter were embedded at depths of 15 to 25 mm, the generated singlet oxygen exceeded the cell death threshold across all tumor voxels. Shallow tumors between 15 and 20 mm can be treated with 15 or fewer irradiations, whereas deep tumors between 20 and 25 mm are estimated to require up to 45 irradiations.

Conclusions: This virtual clinical trial using 150 digital phantoms suggests that NIR-PDT with UCQRs offers a promising, minimally invasive alternative for treating breast cancer.