Photodynamic therapy outcome modelling for patients with spinal metastases: a simulation-based study

Abstract

Spinal metastases often occur in the advanced stages of breast, lung or prostate cancer, resulting in a significant impact on the patient’s quality of life. Current treatment modalities for spinal metastases include both systemic and localized treatments that aim to decrease pain, improve mobility and structural stability, and control tumour growth. With the development of non-toxic photosensitizer drugs, photodynamic therapy (PDT) has shown promise as a minimally invasive non-thermal alternative in oncology, including for spinal metastases. To apply PDT to spinal metastases, predictive algorithms that optimize tumour treatment and minimize the risk of spinal cord damage are needed to assess the feasibility of the treatment and encourage a broad acceptance of PDT in clinical trials. This work presents a framework for PDT modelling and planning, and simulates the feasibility of using a BPD-MA mediated PDT to treat bone metastases at two different wavelengths (690 nm and 565 nm). An open-source software for PDT planning, PDT-SPACE, is used to evaluate different configurations of light diffusers (cut-end and cylindrical) fibres with optimized power allocation in order to minimize the damage to spinal cord or maximize tumour destruction. The work is simulated on three CT images of metastatically involved vertebrae acquired from three patients with spinal metastases secondary to colorectal or lung cancer. Simulation results show that PDT at a 565 nm wavelength has the ability to treat 90% of the metastatic lesion with less than 17% damage to the spinal cord. However, the energy required, and hence treatment time, to achieve this outcome with the 565 nm is infeasible. The energy required and treatment time for the longer wavelength of 690 nm is feasible ($${\sim }\,40$$ ∼ 40 min), but treatment aimed at 90% of the metastatic lesion would severely damage the proximal spinal cord. PDT-SPACE provides a simulation platform that can be used to optimize PDT delivery in the metastatic spine. While this work serves as a prospective methodology to analyze the feasibility of PDT for tumour ablation in the spine, preclinical studies in an animal model are ongoing to elucidate the spinal cord damage extent as a function of PDT dose, and the resulting short and long term functional impairments. These will be required before there can be any consideration of clinical trials.

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

“…An optical scanning method represents a low-cost and effective alternative to CT and MRI for the construction of a model of organ walls [142,143]. For example, the results of PDT modeling using an individual 3D model of metastatically affected vertebrae obtained from three patients demonstrated the potential for the treatment of 90% of metastatic lesions with less than 17% spinal cord damage [113]. The integration of machine learning algorithms in the PDT planning system enables the prediction of changes in tissue optical properties with an error rate of less than 6%, thereby enhancing the reliability of the predicted PDT outcome by significantly reducing the discrepancy between the predicted and ideal plan outcomes [144].…”

“…The requisite energy and treatment time for the longer wavelength of 690 nm are attainable, but treatment targeting 90% of the metastatic lesion could result in significant damage to the proximal spinal cord. PDT-SPACE has provided a modeling platform that can be utilized to optimize PDT of metastatic spinal lesions [113].…”

First Clinical Report of the Intraoperative Macro- and Micro-Photodiagnosis and Photodynamic Therapy Using Talaporfin Sodium for a Patient with Disseminated Lumbar Medulloblastoma

“…When we search articles in PubMed using the key words “Spinal tumor”, “Spinal cord tumor” and “PDT”, most of the identified articles reported the efficacy and safety of PDT for spinal “vertebral” metastatic tumors as preclinical and clinical research [ 13 , 14 , 15 , 16 , 17 ]. However, there were no articles analyzing the efficacy of PDT for spinal “cord” tumors.…”

The Value of 320-Slice Spiral Computed Tomography Perfusion Imaging in Staging and Long-Term Dynamic Evaluation of Breast Cancer

“…Most breast adenocarcinoma patients will undergo CT examination before surgery, which can not only be used to assess the extent of breast adenocarcinoma lesions. In addition, it can also detect the presence of metastases in many organs and bone masses such as distant skin, chest wall, regional lymph nodes (axillary, internal mammary, and supraclavicular lymph nodes), so as to make systematic preoperative clinical staging and arrange follow-up treatment plans [ 16 ]. 320-slice spiral CT is an auxiliary diagnostic imaging tool, which has strong clinical value in the preoperative evaluation of breast adenocarcinoma.…”