Tumors of the Skeletal System

Canine appendicular osteosarcoma is commonly treated with limb amputation; however, limb‐sparing options are frequently desired or necessary for a subset of patients. We evaluated 123 patients and 130 sites treated with stereotactic body radiation therapy (SBRT). Eighty‐two out of 98 dogs (84%) had maximum lameness improvement at a median of 3 weeks for a median of 6 months duration. Histopathologic evaluation of available samples from amputation or necropsy revealed >80% tumor necrosis in 50% of limbs consistent with local disease control. Of evaluable patients, 41% fractured and 21% pursued an amputation after treatment. Fine needle aspirate (n = 52) and needle core biopsy (n = 28) did not result in increased fracture risk compared to those without tumor sampling (n = 50). Median survival time (MST) was 233 days and time to first event was 143 days. Gross tumor volume and planned target volume were significantly inversely associated with survival and tumor location was significantly associated with survival. Dogs with salvage amputation had a significantly longer MST compared to those without (346 vs 202 days; P = .04). The presence of metastatic disease at the time of treatment in 15 dogs did not significantly impact survival time (200 vs 237 days without metastasis; P = .58). Skin side effects correlated significantly with dose with 33% of patients with acute grade 3 effects developing consequential late grade 3 effects. While SBRT improves lameness in most patients, further investigation is needed to identify candidates with minimal early fracture risk prior to initiating therapy.

Section: Introductionmentioning

confidence: 99%

Outcome and prognosis for canine appendicular osteosarcoma treated with stereotactic body radiation therapy in 123 dogs

Martin

Griffin

Custis

et al. 2021

“…With an estimated incidence of >10 000 new cases per year, osteosarcoma (OS) is the most common primary bone tumour in dogs 1 . Despite aggressive treatment involving limb amputation and systemic chemotherapy, 90% of dogs succumb to chemotherapeutic resistant metastatic disease 2 .…”

Section: Introductionmentioning

confidence: 99%

The selective inhibitor of nuclear export (SINE) verdinexor exhibits biologic activity against canine osteosarcoma cell lines

Breitbach

Louke

Tobin

et al. 2021

Verdinexor (KPT‐335) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) compound that inhibits the function of the nuclear export protein Exportin 1 (XPO1/CRM1). In the present study, we sought to characterize the expression of XPO1 in primary canine osteosarcoma (OS) tumour samples, OS cell lines and normal osteoblasts and evaluate the in vitro activity of verdinexor alone or in combination with doxorubicin. Canine OS cell lines and a subset of primary OS tumours showed increased XPO1 transcript and protein expression as compared with normal canine osteoblast cells. All canine OS cell lines exhibited dose‐dependent growth inhibition and increased caspase 3,7 activity in response to low nanomolar concentrations of verdinexor (IC50 concentrations ranging from 21 to 74 nM). Notably, growth inhibition of normal canine osteoblast cell lines treated with verdinexor was observed at high micromolar concentrations (IC50 = 21 μM). The combination of verdinexor and doxorubicin resulted in potent inhibition of cell viability and demonstrated synergetic activity in three canine OS cell lines. Concordantly, OS cell lines showed increased γH2A.X foci following treatment with doxorubicin and recovery in verdinexor compared with cells treated with doxorubicin and recovered in normal media for 24 hours. These findings demonstrate that verdinexor has biologic activity against canine OS cell lines at physiologically relevant doses and suggest that XPO1 inhibition in combination with standard doxorubicin treatment offers promising potential for chemotherapeutic intervention in canine OS.

“…Osteosarcoma (OSA) affects over 10 000 dogs each year in the United States. 1 In Sweden, the incidence rate is 27.2 dogs per 100 000 each year 2 and in Poland the percentage of dogs diagnosed with OSA in two clinics was estimated to be 2.7% to 10.7%, depending on breed. 3 The distal radius is one of the most common anatomic sites for appendicular OSA.…”

Section: Introductionmentioning

confidence: 99%

“…3 The distal radius is one of the most common anatomic sites for appendicular OSA. 1 While amputation arguably remains the standard of care for treating the primary tumour, some dogs are not good candidates because of concurrent orthopaedic or neurologic disease. Amputation can also lead to some negative sequelae.…”

Section: Introductionmentioning

confidence: 99%

Limb‐sparing in dogs using patient‐specific, three‐dimensional‐printed endoprosthesis for distal radial osteosarcoma: A pilot study

Séguin¹,

Pinard²,

Lussier

et al. 2019

Limb‐sparing for distal radial osteosarcoma has a high rate of complications. Using personalized three‐dimensional (3D)‐printed implants might improve outcome. The goals of this study were to optimize use of patient‐specific, 3D‐printed endoprostheses for limb‐sparing in dogs in the clinical environment and to report the outcome. This was a pilot study where five client‐owned dogs were enrolled. Computed tomography (CT) of the thoracic limbs was performed, which was used to create patient‐specific endoprostheses and cutting guides, and repeated on the day of surgery. Intra‐arterial (IA) carboplatin was introduced in the clinical management. Limb‐sparing was performed. Outcome measures were time required to produce the endoprosthesis and cutting guide, fit between cutting guide and endoprosthesis with host bones, gait analysis, size of the tumour, percent tumour necrosis, complications, disease‐free interval (DFI) and survival time (ST). Four dogs received IA carboplatin. Excessive tumour growth between planning CT and surgery did not occur in any dog. The interval between the CT and surgery ranged from 14 to 70 days. Fit between the cutting‐guide and endoprosthesis with the host bones was good to excellent. At least one complication occurred in all dogs. Two dogs were euthanized with STs of 192 and 531 days. The other dogs were alive with a follow up of 534 to 575 days. IA chemotherapy is a promising strategy to minimize the risk of excessive tumour growth while waiting for the endoprosthesis and cutting‐guide to be made. The design of the cutting‐guide was critical for best fit of the endoprosthesis with host bones.