Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

Advances in veterinary radiation therapy: targeting tumors and improving patient comfort.

Newer technology, such as intensity-modulated radiation therapy, can dramatically decrease acute radiation side effects, making patients more comfortable during and after treatment. Stereotactic radiation therapy for definitive treatment can be delivered in 1 to 5 fractions, with minimal radiation-associated effects. Image-guided radiation therapy can be used to direct treatment in locations previously not amenable to radiation therapy. Traditional fractionated radiation therapy remains the most commonly available type in veterinary medicine and is the standard of care for many tumors. This article discusses the role of advancements in the treatment of veterinary cancer patients and reviews more traditional radiation treatment.

Stereotactic body radiation therapy for treatment of injection-site sarcomas in cats: 11 cases (2008-2012).

OBJECTIVE: To evaluate outcomes of stereotactic body radiation therapy (SBRT) in cats with injection-site sarcomas (ISS) via assessment of local responses and recurrences, survival times, and complications. DESIGN: Retrospective case series. ANIMALS: 11 cats with ISS. PROCEDURES: Medical records of cats that were treated with SBRT for ISS between June 2008 and July 2012 were reviewed; information on patient demographics (age, sex, and breed), oncological histories (including prior treatment and histologic grade), details of SBRT plans (tumor volume, treatment field sizes, and prescription), response to treatment (including toxicoses), progression-free intervals, and survival times were extracted. RESULTS: Acute radiation-associated toxicoses were infrequent and limited to mild, self-limiting dermatitis and colitis in 2 and 1 of the 11 cats, respectively. No late radiation-associated toxicoses were observed. The objective response rate was 8 of 11 cats; these patients either had a partial or complete response as determined on the basis of CT or physical examination findings. The median progression-free interval was 242 days, and the median overall survival time was 301 days; median follow-up time of censored subjects was 173 days. CONCLUSIONS AND CLINICAL RELEVANCE: SBRT was completed in 3 to 5 days and was well tolerated when used to treat cats with ISS. Measurable tumor responses were achieved in most cats in this study. Stereotactic body radiation therapy provided a means for palliation of ISS; further investigation is required to determine whether SBRT is a valid treatment option for downstaging disease prior to definitive surgery.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

OBJECTIVE: To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. ANIMALS: 26 athymic nude rats. PROCEDURES: 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. RESULTS: Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Repeatability of a planning target volume expansion protocol for radiation therapy of regional lymph nodes in canine and feline patients with head tumors.

For canine and feline patients with head tumors, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study was to assess the repeatability of a planning target volume (PTV) expansion protocol for these LNs. Two CT image sets from 44 dogs and 37 cats that underwent radiation therapy for head tumors were compared to determine LN repositioning accuracy and precision; planning-CT (for radiation therapy planning) and cone-beam CT (at the time of actual treatment sessions). Eleven percent of dogs and 65% of cats received treatment to their LNs. In dogs, the mandibular LNs were positioned more caudally (P = 0.0002) and the right mandibular and right retropharyngeal LNs were positioned more to the left side of the patient (P = 0.00015 and P = 0.003, respectively). In cats, left mandibular LN was positioned higher (toward roof) than the planning-CT (P = 0.028). In conclusion, when the patient immobilization devices and bony anatomy matching are used to align the primary head target and these LNs are treated simultaneously, an asymmetrical PTV expansion that ranges 4-9 mm (dogs) and 2-4 mm (cats), depending on the directions of couch movement, should be used to include the LNs within the PTV at least 95% of the time.