Osteoradionecrosis and Radiation Induced Bone Tumors Following Orthovoltage Radiation Therapy in Dogs

Abstract

Osteoradionecrosis and radiation-induced bone tumors are rare complications of radiation therapy. Little information regarding these complications is available in veterinary medicine. We characterized these complications and investigated risk factors in 119 dogs (122 sites) that received definitive orthovoltage radiation therapy to appendicular sites. Long-term survival was expected in all dogs. The complications of interest were osteoradionecrosis and secondary bone tumor, evaluated radiographically, histopathologically, or both. Complication rates were estimated using the Kaplan-Meier product-limit method, and Fisher's exact test or chi-square test was used to compare the complication rate. The median survival time was 1405 days, with median follow-up duration of 657 days. There were 10 radiation-induced bone tumors and five radiation-induced fractures, with two dogs developing both, for an overall complication rate of 11%. The latent period ranged from 1.2 to 6.4 years for osteoradionecrosis and from 2.6 to 8.7 years for radiation-induced bone tumor. Complications were significantly higher in the humerus (P < 0.0001), and in dogs younger than 7 years (P = 0.014). Similar assessment of complications in dogs irradiated with megavoltage photons or electrons are needed.

Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector–transduced CD34+ cells

“…[63][64][65] One canine study reported osteosarcomas developing in almost 10% of dogs followed for 1.2 to 6.4 years after high-dose radiation therapy. 66 So although we remain concerned regarding the occurrence of these tumors, the evidence so far strongly suggests they are linked to the irradiation, not the SIV gene transfer vector. The development of effective nonmyeloablative, nonmutagenic, and less toxic conditioning regimens, particularly for nonmalignant target diseases, is crucial for any wide application of gene therapy targeting HSCs.…”

Oral and maxillofacial osteosarcoma in dogs: a review

“…While the aetiology of osteosarcoma is still uncertain in dogs and humans, several contributing factors have been suggested. Factors such as ionizing radiation, genetics, bone tumour viruses, chemicals, chronic irritation due to fractures repaired by metallic implants, bone infarcts, skeletal diseases or disorders as well as body size and sex are believed to be involved in pathogenesis …”

“…While the aetiology of osteosarcoma is generally unknown in both dogs and humans, a proposed association with ionizing radiation has been reported with oral and maxillofacial osteosarcomas . Other reported possible aetiologies include genetics, pre‐existing bone disease, trauma, bone viruses and metallic bone implants …”

The bone regenerative capacity of canine mesenchymal stem cells is regulated by site-specific multilineage differentiation

“…45 Additionally, long-term use of bone antiresorptives is often complicated by jaw osteonecrosis while non-oral bones are spared. 46 Since dogs readily develop jaw osteoradionecrosis, 47, 48 it is not unlikely that they may be susceptible to the same pathological features as humans because dogs are exposed to similar external and environmental factors as humans.…”