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1.
Sci Rep ; 11(1): 17871, 2021 09 09.
Article in English | MEDLINE | ID: mdl-34504208

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 ([Formula: see text] 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.


Subject(s)
Neoplasm Metastasis/pathology , Photochemotherapy , Photosensitizing Agents/therapeutic use , Spinal Neoplasms/therapy , Humans , Photochemotherapy/methods , Prospective Studies , Quality of Life , Spinal Neoplasms/secondary , Spine/pathology , Verteporfin/therapeutic use
2.
Curr Osteoporos Rep ; 18(6): 705-715, 2020 12.
Article in English | MEDLINE | ID: mdl-33074529

ABSTRACT

PURPOSE OF REVIEW: Skeletal metastasis involves the uncoupling of physiologic bone remodeling resulting in abnormal bone turnover and radical changes in bony architecture, density, and quality. Bone strength assessment and fracture risk prediction are critical in clinical treatment decision-making. This review focuses on bone tissue and structural mechanisms altered by osteolytic metastasis and the resulting changes to its material and mechanical behavior. RECENT FINDINGS: Both organic and mineral phases of bone tissue are altered by osteolytic metastatic disease, with diminished bone quality evident at multiple length-scales. The mechanical performance of bone with osteolytic lesions is influenced by a combination of tissue-level and structural changes. This review considers the effects of osteolytic metastasis on bone biomechanics demonstrating its negative impact at tissue and structural levels. Future studies need to assess the cumulative impact of cancer treatments on metastatically involved bone quality, and its utility in directing multimodal treatment planning.


Subject(s)
Bone Neoplasms/physiopathology , Bone Neoplasms/secondary , Osteolysis/physiopathology , Animals , Biomechanical Phenomena , Humans
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