Beyond bisphosphonates: photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue.
Breast cancer patients commonly develop metastases in the spine, which compromises its mechanical stability and can lead to skeletal related events. The current clinical standard of treatment includes the administration of systemic bisphosphonates (BP) to reduce metastatically induced bone destruction. However, response to BPs can vary both within and between patients, which motivates the need for additional treatment options for spinal metastasis. Photodynamic therapy (PDT) has been shown to be effective at treating metastatic lesions secondary to breast cancer in an athymic rat model, and is proposed as a treatment for spinal metastasis. The objective of this study was to determine the effect of PDT, alone or in combination with previously administered systemic BPs, on the structural and mechanical integrity of both healthy and metastatically involved vertebrae. Human breast carcinoma cells (MT-1) were inoculated into athymic rats (day 0). At 14 days, a single PDT treatment was administered, with and without previous BP treatment at day 7. In addition to causing tumor necrosis in metastatically involved vertebrae, PDT significantly reduced bone loss, resulting in strengthening of the vertebrae compared to untreated controls. Combined treatment with BP + PDT further enhanced bone architecture and strength in both metastatically involved and healthy bone. Overall, the ability of PDT to both ablate malignant tissue and improve the structural integrity of vertebral bone motivates its consideration as a local minimally invasive treatment for spinal metastasis secondary to breast cancer.
Won
Emily
E
Orthopaedic Biomechanics Laboratory, Division of Orthopaedic Surgery, Sunnybrook Health Sciences Centre, Room UB-19, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.
Wise-Milestone
Lisa
L
Akens
Margarete K
MK
Burch
Shane
S
Yee
Albert J M
AJ
Wilson
Brian C
BC
Whyne
Cari M
CM
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009336:Necrosis; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D011923:Rats, Nude; D013125:Spinal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D000077362:Verteporfin; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D000077211:Zoledronic Acid