Sumeyye TOYGA(1), Evrim EGEDEN(2), Funda YILDIRIM(3), E. Handan ZEREN(4), Zuleyha AKGUN(5)
(1)Istanbul University-Cerrahpasa, Faculty of Veterinary Medicine, Graduate School of Education, Department of Pathology, Buyukcekmece, 34500, Istanbul, Turkey
(2)Ada Veterinary Clinic, Besiktas, 34330 Istanbul, Turkey
(3)Istanbul University-Cerrahpasa Faculty of Veterinary Medicine, Department of Pathology, Buyukcekmece, 34500 Istanbul, Turkey
(4)Acibadem Mehmet Ali Aydinlar University, Faculty of Medicine, Department of Pathology, Atasehir, 34758 Istanbul, Turkey
(5)Istanbul Bilgi University, Department of Radiation Oncology, Sisli, 34060, Istanbul, Turkey
E-Mail: toygasumeyye@gmail.com
INTRODUCTION Osteosarcoma is responsible for 85% of malignant bone tumors in dogs and approximately 70% in cats. Although the age range of osteosarcoma in dogs is wide, the average age of occurrence is 7 years and it is reported that it develops more frequently in giant breeds. Even if the diagnosis appears to be early when the primary mass is small, the outcome is almost always fatal due to its rapid metastasizing character. Clinical signs reflect the location of the lesion, with lameness being the earliest symptom in most cases. Radiological examinations are helpful in diagnosis[1]. Various prognostic factors have been reported, including elevated serum alkaline phosphatase (ALP), location of the affected bone, age, and weight. The diagnostic gold standard for osteosarcoma is histopathological examination. In the treatment of osteosarcoma, surgery (limb amputation or limb sparing surgery), radiotherapy and chemotherapy methods are used alone or usually in combination. In addition, bisphosphonates are known to inhibit osteoclast function to reduce bone resorption and have direct anti- tumor effects, including inhibiting tumor cell proliferation, adhesion, and invasion[2]. For dogs that are poor candidates for amputation or limb-sparing procedures, stereotactic radiation therapy has been considered an advanced treatment technique. Stereotactic radiation therapy involves delivering high-dose radiation fractions (20 to 30 Gy) to the target area using an external beam of radiation, sparing surrounding tissues with submillimeter accuracy. It was aimed to present the treatment with stereotactic radiation therapy in a patient diagnosed with appendicular osteosarcoma.
MATERIAL METHOD
The case consists of an 8-year-old female Cane Corso Italian Mastiff dog weighing 60 kg. There is no known cancer case defined in the family history of the patient who was referred to our clinic with the suspicion of osteosarcoma. Clinical examination revealed lameness, local swelling and pain in the left hind foot. Samples were taken from this area with the fine needle aspiration biopsy technique, smear preparations were prepared and stained with MayGrünwald & Giemsa and examined microscopically. With the detection of neoplastic cells in the cytological examination, a biopsy sample was taken for histopathological examination under general anesthesia. The biopsy specimen was fixed in 10% formalin solution for 24 hours. Then, the tissue sample was embedded in paraffin blocks after routine tissue follow-up procedures. Sections of 3-4 μm thickness were taken from paraffin blocks and stained with Hematoxylin-Eosin. The histopathological diagnosis of osteosarcoma was performed and the entire skeleton, thoracic and abdominal cavity were visualized by x-ray. Computed tomography imaging performed under general anesthesia was applied to the patient who was suitable for anesthesia after cardiac and hematological examination, and radiation therapy was planned. A 36 Gy stereotactic body radiation therapy protocol was created for the case in 3 fractions. Computed tomography imaging control plan was created in 6-month periods in terms of oncological evaluation.
The case consists of an 8-year-old female Cane Corso Italian Mastiff dog weighing 60 kg. There is no known cancer case defined in the family history of the patient who was referred to our clinic with the suspicion of osteosarcoma. Clinical examination revealed lameness, local swelling and pain in the left hind foot. Samples were taken from this area with the fine needle aspiration biopsy technique, smear preparations were prepared and stained with MayGrünwald & Giemsa and examined microscopically. With the detection of neoplastic cells in the cytological examination, a biopsy sample was taken for histopathological examination under general anesthesia. The biopsy specimen was fixed in 10% formalin solution for 24 hours. Then, the tissue sample was embedded in paraffin blocks after routine tissue follow-up procedures. Sections of 3-4 μm thickness were taken from paraffin blocks and stained with Hematoxylin-Eosin. The histopathological diagnosis of osteosarcoma was performed and the entire skeleton, thoracic and abdominal cavity were visualized by x-ray. Computed tomography imaging performed under general anesthesia was applied to the patient who was suitable for anesthesia after cardiac and hematological examination, and radiation therapy was planned. A 36 Gy stereotactic body radiation therapy protocol was created for the case in 3 fractions. Computed tomography imaging control plan was created in 6-month periods in terms of oncological evaluation.
FINDINGS
While osteolysis was detected in the left femur distal in the radiographic examination, no macro finding of pulmonary metastasis was found in the thorax radiography (FIGURE 1).
While osteolysis was detected in the left femur distal in the radiographic examination, no macro finding of pulmonary metastasis was found in the thorax radiography (FIGURE 1).
In the examination of the samples taken by needle biopsy, an inflammatory process consisting of erythrocytes, neutrophils, eosinophils, leukocytes and macrophages is accompanied by necrotic debris in places, proteinous and granular smears, few and usually isolated, ovoid, flaking in only one area. Neoplastic cells of mesenchymal origin with round or round nuclei, prominent nucleoli, bare nuclei or extensive pale basophilic cytoplasm were observed (FIGURE 2 AND 3).
In the histopathological examination of tissue biopsy samples obtained from the patient, pleomorphic, hyperchromatic, neoplastic osteoblasts with prominent nucleolus were detected, forming irregular osteoid material. Primitive mesenchymal cell assemblages with rounded or ovoid nuclei and fibrous cytoplasm, which surround the osteoid material in lobular fashion and are also observed focally in some areas, were determined. Necrotic areas were observed in the middle parts of the tumoral tissue. As a result of the histopathological examination, it was concluded that the tumor was a Productive type Osteosarcoma that produced osteoid material (FIGURE 4, 5, 6 AND 7).
When the thorax and whole abdomen were examined with computed tomography imaging under general anesthesia, no pathology was found in the visceral organs. In the distal metaphyseal part of the left femur, a lesion area of approximately 6 cm in size, lytic-expansile in character, showing internal popcorn-like calcifications was observed (FIGURE 8).
In the computed tomography imaging performed at the end of the 6-month period after stereotactic radiotherapy, several lymph nodes with pathological morphology, 13×9 mm in size in the left external iliac chain, and 14×11 mm in the left popliteal fossa were observed in the pelvic region (FIGURE 9).
Pneumonia findings were determined at the end of the second 6-month follow-up period of the patient who underwent chemotherapy protocol during the clinical treatment process. In the control computed tomography examination, a 10×7 cm mass lesion with soft tissue component (FIGURE 10) was detected in the distal metaphyseal area of the left femur, with a size of 10×7 cm. A mass lesion with solid components located in the prevascular area in the upper mediastinum, displacing the upper mediastinal structures to the right, measuring approximately 12×6 cm in size after intravenous contrast agent, was found to be compatible with metastasis.
TREATMENT Both 2 mm pre-contrast and post-contrast CT scans were used for contouring and reverse treatment planning using the Varian Eclipse treatment planning system (Varian Medical Systems, Inc. At-risk organs and gross tumor volume were determined and contoured (Omnipaque 350 mg/200 ml contrast medium was injected iv (0.7-3.9 mL/kg)). Target volumes were subtracted from contours containing organs at risk to meet normal tissue optimization constraints. A 36 Gy stereotactic body radiation therapy protocol was created for the case in 3 fractions. Hematological, biochemical, and C-Reactive protein panels were reviewed regularly prior to each radiation therapy (IDEXX Catalyst Dx® Biochemical Analyzer, IDEXX ProCyte® Hematology Analyzer). For pain management, tramadol 1.5 mg/kg /8h was administered orally. The patient received 36 Gy stereotactic radiation therapy in 3 fractions on Monday, Wednesday and Friday (FIGURE 11).
A decrease in local pain and neoplastic swelling was noted shortly after the first radiation therapy sessions ended. After about 2 weeks, the lameness symptom disappeared. In the ongoing process, controlled and untreated clinical follow-up was performed. Computed tomography imaging performed at the end of the 6-month period revealed pathological formations in the left external iliac chain in the pelvic region. Pamidronate disodium (1-2 mg/kg/28 days iv over a 2-hour period) was administered. Before chemotherapy, ondansetron hydrochloride dihydrate 0.1mg/kg iv slow infusion, dexamethasone 0.5-1 mg/kg iv and cetirizine hydroclari 1 mg/kg oral administration were administered. Chemotherapy sessions were performed iv in 500 ml of saline solution at a dose of 300mg/m2 of Carboplatin. In the chemotherapy protocol created, the process was followed up with blood tests before each session and 7 days after the session. Pulmonary metastasis was observed in the computed tomography control imaging of our case, whose clinical controls continued regularly for 6 months after chemotherapy.
CONCLUSION AND DISCUSSION
It has been reported in various studies that the average survival time of osteosarcoma is 2 months after diagnosis, and it can be prolonged up to 6 months with amputation and chemotherapy. Pulmonary metastasis was detected in the clinical oncological follow-up of our patient, who survived for approximately 2 years with radiotherapy and chemotherapy. Although surgical radical amputation is solution-oriented for pain management and total tumor removal, the inevitability of micrometastasis with the onset of osteosarcoma symptoms also causes a clinical contradiction due to the negative effects of amputation surgery on the quality of life in large breed dogs. On the other hand, we aim to raise awareness with this presentation that stereotactic radiotherapy applications are a successful method recently, and that it has a positive effect on pain management, along with its management, on average survival time and quality of life.
It has been reported in various studies that the average survival time of osteosarcoma is 2 months after diagnosis, and it can be prolonged up to 6 months with amputation and chemotherapy. Pulmonary metastasis was detected in the clinical oncological follow-up of our patient, who survived for approximately 2 years with radiotherapy and chemotherapy. Although surgical radical amputation is solution-oriented for pain management and total tumor removal, the inevitability of micrometastasis with the onset of osteosarcoma symptoms also causes a clinical contradiction due to the negative effects of amputation surgery on the quality of life in large breed dogs. On the other hand, we aim to raise awareness with this presentation that stereotactic radiotherapy applications are a successful method recently, and that it has a positive effect on pain management, along with its management, on average survival time and quality of life.
REFERENCE [1] Ehrhart NP, Ryan SD, Fan TM. Tumors of the skeletal system. In: Withrow SJ, Vail DM, Page RL, eds. Withrow and MacEwen’s Small Animal Clinical Oncology. 5th ed. St Louis: Saunders Elsevier; 2013:463–503. [2] Poon C.A., Matsuyama A., Mutsaers J.A. Recent and current clinical trials in canine appendicular osteosarcoma. Can Vet J 2020;61:301–308
