BONE SCINTIGRAPHY FOR METASTASIS DETECTION IN CANINE OSTEOSARCOMA

The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma.     

SCINTIGRAPHIC DETECTION OF SUBCUTANEOUS METASTASIS IN A DOG WITH APPENDICULAR OSTEOSARCOMA

This report describes the detection of subclinical soft tissue metastasis of an appendicular osteosarcoma in a dog using bone scintigraphy. A 7-year-old spayed female Rottweiler was presented with a biopsy confirmed diagnosis of osteosarcoma. Initial radiographs revealed an aggressive bone lesion of the left distal radius. At presentation, there was no clinical or radiographic evidence of metastasis; however, a nuclear bone scan showed the primary bone lesion of the distal left radius and numerous soft tissue lesions consistent with diffuse soft tissue metastases. A left foreleg amputation was performed and cisplatin chemotherapy was given post-operatively. A second bone scan performed one month following initial presentation showed progression in size and number of soft tissue masses. Many of the lesions had become apparent on physical exam and survey radiographs. Excisional biopsy was performed on one of the soft tissue masses and a diagnosis of metastatic osteosarcoma was made. The dog was euthanized 2 months after initial presentation at the owners request due to deterioration of the animals physical condition.     

A RETROSPECTIVE EVALUATION OF THE RADIOGRAPHIC EVIDENCE OF PULMONARY METASTATIC DISEASE ON INITIAL PRESENTATION IN THE DOG

Thoracic radiographs of 346 dogs, diagnosed as having primary neoplasms, were reviewed for radiographic changes associated with pulmonary metastatic disease at the time of initial presentation. Dogs having radiographic changes of single or multiple interstitial nodular opacities, in the absence of concurrent intrathoracic disease, were considered to have pulmonary metastatic disease. The frequency of metastasis associated with each histologic tumor type was compared by chi-squared analysis. Dogs having primary thyroid carcinomas and transitional cell carcinomas demonstrated the greatest frequency of radiographic changes, 62.5% and 26% respectively. In dogs having a variety of other neoplasms, including nasal adenocarcinomas and cutaneous neoplasms, thoracic radiography proved useful in delineating intercurrent disease and staging, as well as the extent of neoplastic involvement. These results indicate early radiographic evaluation of the thorax should be performed on all dogs with confirmed or suspected primary neoplasms.     

Comparison of concurrent imaging modalities for staging of dogs with appendicular primary bone tumours

This study assessed the use of whole body computed tomography (CT) for the evaluation of metastasis in dogs with primary appendicular bone tumours compared to long bone survey radiography, bone scintigraphy and thoracic radiographs. Fifteen dogs were included in this pilot study. A construct reference standard was used for detection of bone metastasis, and negative thoracic radiographs were compared against CT. Definitive lesions were only identified on bone scintigraphy. Not all lesions agreed with the construct reference standard. No definitive lesions were identified on survey radiographs or CT. Lesions were identified on thoracic CT that were not visible radiographically. Equivocal ground glass pulmonary lesions progressed in three of four cases. Whole body CT was not a suitable alternative to bone scintigraphy; however, it was useful as an adjunctive diagnostic modality. Pulmonary lesions were visible on CT that were not seen radiographically and ground glass pulmonary lesions in dogs should be considered suspicious for metastasis.     

Bone scintigraphy in the initial evaluation of dogs with primary bone tumors

Bone scintigraphy was performed as part of an initial diagnostic evaluation of 70 dogs admitted with primary bone tumors during a 2-year period. Tumors involved major long bones of the appendicular skeleton and included 62 osteosarcomas, 6 fibrosarcomas, and 2 chondrosarcomas. All dogs were free of radiographically detectable pulmonary metastases. Bone scintigraphy was not of value in distinguishing among various types of primary tumors. One dog with an ulnar chondrosarcoma had a scintigraphically detectable occult osseous metastasis or synchronous primary tumor, and 1 dog with osteosarcoma had a scintigraphically detectable lymph node metastasis. Pulmonary metastases were not detected scintigraphically. Of the 70 dogs, 44.3% had areas of increased isotope uptake associated with nonneoplastic disease processes.     

Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985-2004)

OBJECTIVE-To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival. DESIGN-Retrospective case series. ANIMALS-90 dogs with stage III osteosarcoma. PROCEDURES-Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis. RESULTS-Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases. CONCLUSIONS AND CLINICAL RELEVANCE-Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.     

Retropective Evaluation of Survival Time of Dogs with Stage III Osteosarcoma that Undergo Treatment

Introduction:  Stage III osteosarcoma generally carries a grave prognosis. Despite this, some owners elect to treat using palliative or curative intent protocols. The purpose of this study was to determine the survival times for dogs with stage III osteosarcoma that undergo treatment and to evaluate the variables that affect survival time.
Methods:  Retrospective study using the CSU Animal Cancer Center osteosarcoma data base. Search criteria included dogs diagnosed with osteosarcoma 1985–2004 with metastasis at the time of presentation. Dogs were excluded if they were euthanized at the time of diagnosis (13 dogs) or lost to follow‐up (10 dogs). There were 90 cases for analysis. The survival times were compared based on the primary tumor site, site of metastasis, treatment given, age, sex and breed.
Results:  Survival times in days ranged from 0 to 1583 days. The overall median survival time was 76 days. The one‐year, two‐year and three‐year percent survival were 7%, 4.7% and 3.5%, respectively. Treatment included various combinations of chemotherapy, surgery, radiation therapy, bisphosphonates and NSAIDs. Findings included an increased survival time with surgery and adjuvant therapy compared with surgery alone and a decreased survival time with metastasis to the lung or lymph node.
Conclusions:  Treatment of dogs with stage III osteosarcoma can result in variable survival times. Multimodality therapy appears to result in longer survival times. Metastasis to the lung or lymph node correlated with a decreased survival time.     

Canine Osteosarcoma

Osteosarcoma was diagnosed in 38 dogs. Thirty-six tumors originated from the appendicular skeleton and two from the axial skeleton. Nineteen of the dogs were treated with amputation alone, and 19 were treated with amputation and adjuvant chemotherapy consisting of doxorubicin and cisplatin. The 36 dogs with appendicular osteosarcoma had complete amputation of the affected limb, whereas the two dogs with osteosarcoma of the axial skeleton had an en bloc resection. The mean survival of the 19 dogs treated with amputation alone was 218 days (median, 175 days). Ten dogs were alive at 6 months and four survived 1 year. None of the dogs survived longer than 16 months. Radiographic lesions consistent with metastatic osteosarcoma were seen after surgery in the nine dogs in which radiographs were taken. The mean survival of the 19 dogs treated with amputation and chemotherapy was 415 days (median, 300 days). Drug toxicity was not observed. Fifteen dogs were alive at 6 months, seven dogs were alive at 1 year, 5 dogs were alive at 2 years, and two dogs were alive at 3 years or longer. One dog is alive and well at 25 months. Radiographic lesions suggestive of metastatic osteosarcoma developed in the other 18 dogs. The 19 dogs treated with amputation and chemotherapy had significantly longer survival times than the dogs treated with amputation alone.     

Pathologic fracture in dogs with suspected or confirmed osteosarcoma

Objective: To evaluate clinical presentation of pathologic fractures associated with suspected or confirmed osteosarcoma in dogs and to assess treatment and survival times. Study design: Case series. Animals: Dogs (n=25) appendicular pathologic fracture. Methods: Medical records (January 1997–May 2008) of dogs with pathologic fracture associated with a suspected or confirmed osteosarcoma were reviewed. Dogs were included if they had radiographic evidence of a pathologic fracture and a presumptive or definitive diagnosis of osteosarcoma. Radiographic details, histopathology, and/or cytology findings were recorded. Overall median survival time (MST) and MST of treated dogs were calculated. Age, sex, breed, and other concurrent treatment were evaluated. Results: Rottweilers, Irish Wolfhounds, and Greyhounds were the most common breeds represented. Most dogs had minor trauma and 60% had lameness preceding the fracture. Most commonly, fractures were nondisplaced with minimal comminution. None of the dogs had radiographic evidence of pulmonary metastases at admission. Immediate (13 dogs; 52%) and delayed (4; 16%) euthanasia were performed. One dog was not treated and died 90 days after diagnosis. Three dogs (12%) were treated by amputation alone, 1 (4%) with amputation and chemotherapy, and 3 (12%) with internal fixation using an interlocking nail. Overall MST was 1 day (range, 0–623 days) and MST of treated dogs was 406.5 days. Histologic confirmation of osteosarcoma was available in all treated dogs and 6 euthanatized dogs. Conclusions: Treatment of pathologic fracture associated with presumptive osteosarcoma should be considered as an option to amputation or euthanasia if owners desire other options.     

Severe lameness caused by metastatic renal adenocarcinoma of the third phalanx in a Warmblood mare

Malignant osseous neoplasia has been extremely rarely reported in the horse and, therefore, it is not commonly considered as a differential diagnosis for acute lameness. In the present report, a 19‐year‐old Warmblood mare in poor body condition and with a history of chronic haematuria, presumably attributable to renal neoplasia, was referred with acute, progressive, unilateral right forelimb lameness with marked unilateral digital pulsation and metacarpal oedema. No hoof abscess was found. Radiographic examination revealed a well defined osteolytic area in the dorsomedial half of the third phalanx. Dermal laminae at the dorsomedial aspect of the hoof showed a dark red appearance with poor vascularisation. Thoracic radiographs revealed pulmonary nodules. As osseous metastasis of the third phalanx was suspected, the mare was subjected to euthanasia. Post mortem histopathological examination confirmed the diagnosis of primary renal adenocarcinoma with metastasis to the lungs, myocardium, along the perirenal lymphatic tract and to the third phalanx, with extensive osteolysis in the latter location. Post mortem computed tomography of the hoof provided excellent visualisation of the osseous metastasis. The rare possibility of osseous metastatic neoplasia should be included in the differential diagnosis of severe lameness, especially in aged horses with a history of chronic renal disease.     

P‐62 Dermal and subcutaneous extraskeletal osteosarcomas in eight dogs,two cats,and one ferret

Osteosarcoma is a malignant mesenchymal neoplasm characterized by the formation of osteoid tissue. It is the most frequent primary bone tumour in dogs, accounting for nearly 80–85% of all reported long bone appendicular osteosarcomas. Conversely, in cats and other species, osteosarcoma is rare at any site. Extraskeletal osteosarcoma (EOS) is a malignant, osteoid‐producing neoplasm without primary periosteal or bone involvement. These tumours have been described less frequently and occur mainly in the mammary glands of female dogs. Case material was obtained from biopsy records of the Pathology Service at the Veterinary School, Universidad Nacional. The diagnosis of these tumours was based on the absence of clinical, radiological, or pathological evidence of primary bone or glandular involvement. Samples were processed for histopathological examination and stained with H&E. In two cases, immunohistochemistry was performed. Eleven cases were diagnosed with EOS located in two histological locations. The dermal group consisted of three female dogs (two Rottweillers and one Fila Brasileiro), one male German shepherd (mean age of dogs: 5.5 years), two female cats (mixed‐breed and Siamese) of 5 and 11 years of age, respectively, and one 4‐year‐old female ferret. The subcutaneous group consisted of four dogs, two female pit bull terriers and two male dogs (boxer and mixed‐breed), with a mean age of 5 years. The subcutaneous EOS tumours were more aggressive. Three dogs were euthanized due to lung metastasis and the remaining dog was lost to follow‐up. Funding: Self‐funded.     

Comparison of thoracic radiographs and single breath-hold helical CT for detection of pulmonary nodules in dogs with metastatic neoplasia

Imaging studies in people indicate that x-ray computed tomography (CT) is a more sensitive technique than thoracic radiography for the detection of pulmonary metastasic neoplasia. Systematic studies comparing CT and thoracic radiographic techniques in veterinary patients have not been performed. The present retrospective study was designed to directly compare the efficacy of these 2 techniques in detecting pulmonary nodules in dogs. Eighteen dogs with histologically confirmed pulmonary metastatic neoplasia had contemporaneous thoracic radiographs and pulmonary CT scans compared. Quantitative analyses included estimation of pulmonary nodule size, number, and lobar distribution on thoracic radiographs and CT images. Only 9% of CT-detected pulmonary nodules were identified on thoracic radiographs (P < .003). The lower size threshold was approximately 1 mm to detect pulmonary nodules on CT images and 7-9 mm to reliably detect nodules on radiographs (P < .0001). Additionally, pulmonary nodules were detected in a significantly greater number of lung lobes using CT as compared with thoracic radiographs (P < .0001). These data indicate that CT is significantly more sensitive than thoracic radiography for detecting soft-tissue nodules in dogs. As such, thoracic CT should be considered in any patient with neoplasia that has potential for pulmonary metastasis to more reliably stage the disease, particularly when accurate characterization of the extent and distribution of pulmonary metastatic disease affects therapeutic planning.     

Results of Partial Mandibulectomy for the Treatment of Oral Tumors in 142 Dogs

Partial mandibulectomy was performed for the treatment of benign or malignant oral tumors in 142 dogs. Forty-two dogs with a benign tumor (ameloblastoma) had a 22.5 month (range, 6 to 74 months) median disease-free interval, with a 97% 1-year survival rate; there was local recurrence in one dog. Twenty-four dogs with squamous cell carcinoma had a disease-free interval of 26 months (range, 6 to 84 months), with a 91% 1-year survival rate; recurrence and metastasis developed in two dogs and metastatic disease in one dog. Based on survival curves, 37 dogs with a melanoma had a median survival time of 9.9 months (range, 1 to 36 months), with a 21% 1-year survival rate; 20 dogs died or were euthanatized for recurrent or metastatic disease. Twenty dogs with osteosarcoma had a median survival time of 13.6 months (range, 3 to 28 months), with a 35% 1-year survival rate; nine dogs died or were euthanatized for recurrent or metastatic disease. Nineteen dogs with fibrosarcoma had median survival time of 10.6 months (range, 3 to 32 months), with a 50% 1-year survival rate; 12 dogs died or were euthanatized for recurrent or metastatic disease. Results of this and previous studies demonstrated that partial mandibulectomy was effective in prolonging survival and decreasing recurrence for squamous cell carcinoma and ameloblastoma. Progressive disease and corresponding low survival times were common in dogs with melanoma, osteosarcoma, and fibrosarcoma. There were no differences in survival times or the progression of disease among five partial hemimandibulectomy procedures. The high rates of recurrence and metastasis in dogs with these tumors suggest a need for evaluation of ancillary chemotherapy and local radiation therapy to decrease the prevalence of progressive disease.     

Incidence and prognostic importance of lymph node metastases in dogs with appendicular osteosarcoma: 228 cases (1986-2003)

OBJECTIVE: To determine the incidence of regional lymph node metastasis in dogs with appendicular osteosarcoma and determine whether regional lymph node metastasis was associated with shortened disease-free interval or survival time. DESIGN: Retrospective study. ANIMALS: 228 dogs with appendicular osteosarcoma in which regional lymph nodes were examined histologically at the time of limb amputation. PROCEDURE: Information collected from the medical records included signalment; affected site; initial serum alkaline phosphatase activity; whether treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents administered and number of treatments; disease-free interval; and survival time. RESULTS: 10 (4.4%) dogs had histologic evidence of regional lymph node metastasis at the time of amputation. Median disease-free interval for dogs without regional lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node metastasis (318 days; range, 20 to 1,711 days) was significantly longer than median survival time for dogs with lymph node metastasis (59 days; range, 19 to 365 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that regional lymph node metastasis is rare in dogs with appendicular osteosarcoma but that dogs with lymph node metastasis have a poorer prognosis than do dogs without.     

Treatment of Canine Appendicular Osteosarcoma Using Cobalt 60 Radiation and Intraarterial Cisplatin

Twelve dogs with appendicular osteosarcoma were treated with 24–40 Gy of cobalt 60 radiation and two doses of intraarterial cisplatin. Improvement in limb function occurred in four dogs, and three dogs, which had only mild initial lameness, had no worsening of their lameness post-treatment. In nine dogs in which local control was evaluable, eight had local failure, with the median (95% CI) duration of local control being 5.9 (4.6, 6.7) months. Two dogs had metastatic disease before therapy, and an additional nine dogs had metastatic disease at a median time of 6.4 months. Pathologic fracture was present in four dogs; two fractures occurred before treatment and two were documented at the time of tumor recurrence. Median (95% CI) survival time for all 12 dogs was 4.9 (3.4, 6.8) months. Excluding the two dogs with preexisting metastatic disease, median survival time was 6.7 months. Three dogs survived longer than 1 year. This mode of therapy was well tolerated and may be considered an alternative to amputation or limb-sparing surgical procedures in selected dogs with appendicular osteosarcoma.     

Treatment of canine appendicular osteosarcoma using cobalt 60 radiation and intraarterial cisplatin.

Twelve dogs with appendicular osteosarcoma were treated with 24-40 Gy of cobalt 60 radiation and two doses of intraarterial cisplatin. Improvement in limb function occurred in four dogs, and three dogs, which had only mild initial lameness, had no worsening of their lameness post-treatment. In nine dogs in which local control was evaluable, eight had local failure, with the median (95% CI) duration of local control being 5.9 (4.6, 6.7) months. Two dogs had metastatic disease before therapy, and an additional nine dogs had metastatic disease at a median time of 6.4 months. Pathologic fracture was present in four dogs; two fractures occurred before treatment and two were documented at the time of tumor recurrence. Median (95% CI) survival time for all 12 dogs was 4.9 (3.4, 6.8) months. Excluding the two dogs with preexisting metastatic disease, median survival time was 6.7 months. Three dogs survived longer than 1 year. This mode of therapy was well tolerated and may be considered an alternative to amputation or limb-sparing surgical procedures in selected dogs with appendicular osteosarcoma.     

A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9–15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.     

Nuclear medical bone imaging and targeted radiography for evaluation of skeletal neoplasms in 23 dogs

Nuclear medical bone imaging was used in combination with targeted radiography to detect metastatic or multicentric lesions in 23 dogs with skeletal neoplasms. Each dog with a radiographically diagnosed skeletal neoplasm was injected with Technetium-99m labeled methylene diphosphonate (99mTc-MDP) (15.0 mCi intravenously) for whole body imaging. All areas with increased uptake of 99mTc-MDP were radiographed. In 19 dogs, the amount of bone shaft involvement in primary sites indicated by bone imaging was larger than the amount indicated by radiography. Eighteen dogs had secondary areas of increased 99mTc-MDP uptake, six of which had secondary areas that were suspected radiographically to be neoplastic. Four dogs had lesions characterized histologically as neoplasia, one as bone infarction and one as normal cortical bone. Positive predictive value for this strategy was 66.7%. Results of this study suggest that nuclear medical bone imaging with targeted radiography is a quick, noninvasive technique with a good positive predictive value for evaluation of the skeleton for metastatic or multicentric sites of neoplasia.     

Detection of synchronous primary tumours and previously undetected metastases in 736 dogs with neoplasia undergoing CT scans for diagnostic,staging and/or radiation treatment planning purposes

The purpose of our study was to describe synchronous primary tumours and previously undetected metastases in 736 dogs with confirmed neoplasia in which computed tomography (CT) scans were performed for diagnostic, staging and/or radiation treatment planning purposes. All CTs were reviewed by a radiologist. Tumour‐associated CT abnormalities were detected in 38/736 (5%), including confirmed or suspected synchronous primary neoplasms (n = 24), metastases of the primary tumour (n = 9) or both (n = 3). In lymph nodes (LN) that were considered abnormal on CT scan and were aspirated, 23% contained metastasis, and 6% of ‘normal’ appearing LN that were aspirated contained metastasis. Thorough evaluation of CTs and routine aspiration of regional LN are critical because results affect recommendations to perform additional staging tests and treatment for the primary and secondary tumour(s).