Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Abstract

The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with μCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation.