Treatment of Canine Osseous Tumors with Photodynamic Therapy: A Pilot Study

Photodynamic therapy uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. Owing to the limitations of light penetration, it is unknown whether photodynamic therapy can treat large osseous tumors. We determined whether photodynamic therapy can induce necrosis in large osseous tumors, and if so, to quantify the volume of treated tissue. In a pilot study we treated seven dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with MRI before and 48 hours after treatment, and the volumes of hypointense regions were compared. The treated limbs were amputated immediately after imaging at 48 hours and sectioned corresponding to the MR axial images. We identified tumor necrosis histologically; the regions of necrosis corresponded anatomically to hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after photodynamic therapy was 21,305 mm3 compared with a pretreatment volume of 6108 mm3. These pilot data suggest photodynamic therapy penetrates relatively large canine osseous tumors and may be a useful adjunct for treatment of bone tumors

Repeated freeze–thaw cycles reduce the survival rate of osteocytes in bone-tendon constructs without affecting the mechanical properties of tendons

Frozen bone-patellar tendon bone allografts are useful in anterior cruciate ligament reconstruction as the freezing procedure kills tissue cells, thereby reducing immunogenicity of the grafts. However, a small portion of cells in human femoral heads treated by standard bone-bank freezing procedures survive, thus limiting the effectiveness of allografts. Here, we characterized the survival rates and mechanisms of cells isolated from rat bones and tendons that were subjected to freeze–thaw treatments, and evaluated the influence of these treatments on the mechanical properties of tendons. After a single freeze–thaw cycle, most cells isolated from frozen bone appeared morphologically as osteocytes and expressed both osteoblast- and osteocyte-related genes. Transmission electron microscopic observation of frozen cells using freeze-substitution revealed that a small number of osteocytes maintained large nuclei with intact double membranes, indicating that these osteocytes in bone matrix were resistant to ice crystal formation. We found that tendon cells were completely killed by a single freeze–thaw cycle, whereas bone cells exhibited a relatively high survival rate, although survival was significantly reduced after three freeze–thaw cycles. In patella tendons, the ultimate stress, Young’s modulus, and strain at failure showed no significant differences between untreated tendons and those subjected to five freeze–thaw cycles. In conclusion, we identified that cells surviving after freeze–thaw treatment of rat bones were predominantly osteocytes. We propose that repeated freeze–thaw cycles could be applied for processing bone-tendon constructs prior to grafting as the treatment did not affect the mechanical property of tendons and drastically reduced surviving osteocytes, thereby potentially decreasing allograft immunogenecity

Clinical effectiveness of Enneking appropriate versus Enneking inappropriate procedure in patients with primary osteosarcoma of the spine: a systematic review with meta-analysis

Purpose Primary osteosarcoma of the spine is a rare osseous tumour. En bloc resection, in contrast to intralesional resection, is the only procedure able to provide Enneking appropriate (EA) margins, which has improved local control and survival of patients with primary osteosarcoma of the spine. The objective of this study is to compare the risk of local recurrence, metastases development and survival in patients with primary osteosarcoma of the spine submitted to Enneking appropriate (EA) and Enneking inappropriate (EI) procedures. Methods A systematic search was performed on EBSCO, PubMed and Web of Science, between 1966 and 2018, to identify studies evaluating patients submitted to resection of primary osteosarcoma of the spine. Two reviewers independently assessed all reports. The outcomes were local recurrence, metastases development and survival at 12, 24 and 60 months. Results Five studies (108 patients) were included for systematic review. These studies support the conclusion that EA procedure has a lower local recurrence rate (RR 0.33, 95% CI 0.17-0.66), a lower metastases development rate (RR 0.39, 95% CI 0.17-0.89) and a higher survival rate at 24 months (RR 1.78, 95% CI 1.24-2.55) and 60 months (RR 1.97, 95% CI 1.14-3.42) of follow-up; however, at 12 months, there is a non-significant difference. Conclusions EA procedure increases the ratio of remission and survival after 24 months of follow-up. Multidisciplinary oncologic groups should weigh the morbidity of an en bloc resection, knowing that in the first year the probability of survival is the same for EA and EI procedures. Graphic abstract These slides can be retrieved under Electronic Supplementary Material

Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years

Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m(2)), cisplatin (90 mg/m(2)), and doxorubicin (75 mg/m(2)). 3 cycles were administered post-operatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m(2)) as a salvage strategy. Results With a median follow-up of 77 months for survivors, the estimated metastasis-free and sarcoma-related survival at 5 years was 70% and 76%, respectively. 53 patients were treated with limb salvage surgery or rotationplasty and 2 patients experienced a local recurrence. 3 toxic deaths were recorded, all related to acute toxicity from chemotherapy. The 5-year metastasis-free survival of poor histological responders receiving add-on treatment with ifosfamide was 47%, as compared to 89% for good histological responders. Interpretation Outcome from the SSG XIV protocol compares favorably with the results of previous SSG trials and other published osteosarcoma trials. However, salvage therapy given to poor responders did not improve outcome to a similar degree as for good responders. In a multi-institutional setting, more than four-fifths of the patients were operated with limb salvage surgery or rotationplasty, with few local recurrences