Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow‐up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20–24 Gy to the central portion of the tumor. Thirty‐two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment‐associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross‐sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330–708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.     

Stereotactic radiosurgery for treatment of osteosarcomas involving the distal portions of the limbs in dogs

Stereotactic radiosurgery (SRS) involves precise delivery of a single large dose of radiation to a designated tumor target. This report describes use of SRS in combination with a frameless stereotactic localization system to treat 11 dogs with appendicular osteosarcomas. Five dogs were treated with SRS alone; 6 were treated with a combination of SRS and chemotherapy. Overall median survival time was 363 days (range, 145 to 763 days), with 6 dogs still alive 90, 142, 234, 367, 633, and 763 days after SRS. Limb function was good or excellent in all 6 dogs that were still alive. Results in these dogs suggest that SRS may be a viable option for dogs with appendicular osteosarcoma, with the potential to provide long-term local tumor control and improvement in limb function, especially when combined with chemotherapy. Because of the destructive nature of osteosarcoma and limitations of SRS, dogs with tumors that are small and have caused minimal bone destruction would likely be the best candidates for this procedure.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

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.     

Outcome after repair of a sarcoma-related pathologic fracture in dogs: a Veterinary Society of Surgical Oncology Retrospective Study

Objective: To report outcome in dogs after internal fixation of a sarcoma‐related pathologic fracture of the appendicular skeleton. Study Design: Multi‐institutional case series. Animals: Dogs (n=16). Methods: Medical records of participating VSSO members were reviewed for dogs with pathologic fracture associated with a confirmed bone sarcoma of the appendicular skeleton repaired by external or internal fixation. Dogs were included if they had a histological diagnosis of osteosarcoma or sarcoma and excluded if they had radiation before fracture. Data collected were analyzed for signalment, fracture location, staging performed, method of fracture fixation, histopathology, adjunctive treatment and outcome. Results: Signalment and fracture location of 16 dogs that met the inclusion criteria was similar to dogs with appendicular OSA without fracture. One of 14 dogs had pulmonary metastasis and 3 of 5 dogs had bone metastasis. Bone plate or interlocking nail were used for repair in 12 dogs. Limb use immediately after surgery in 13 dogs was good (4), weight‐bearing but lame (7) and non‐weight bearing (2). Adjunctive therapy was administered in 5 dogs (chemotherapy, 3; radiation, 4; pamidronate, 3). Survival time ranged from 18 to 897 days; median survival was 166 days. Conclusions: Repair of pathologic fracture can result in palliation and prolonged survival.     

Proximal radial and distal humeral osteosarcoma in 12 dogs

Twelve dogs were diagnosed with osteosarcoma of the proximal radius or distal humerus from 1990 to 2002, representing 1.0% of all dogs diagnosed with appendicular osteosarcoma. The median body weight (29.8 kg) was significantly less than that of dogs with appendicular osteosarcoma at other sites. Ten dogs were treated with amputation and chemotherapy. These dogs had a metastatic rate of 60%, a median metastasis-free interval of 356 days, and a median survival time of 824 days. There were no significant differences in metastasis-free interval or survival time between dogs with osteosarcoma of the proximal radius or distal humerus and dogs with appendicular osteosarcoma at other sites.     

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.     

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.     

Linac‐based stereotactic radiation therapy for canine non‐lymphomatous nasal tumours: 29 cases (2013‐2016)

Twenty‐nine dogs were treated with linac‐based stereotactic radiation therapy (SRT) for non‐lymphomatous nasal tumours. Only dogs with a follow‐up time >365 days were included in this retrospective analysis. No dogs had evidence of distant metastasis at diagnosis. Treatment was planned and a total of 30 Gy in 3 daily 10 Gy fractions was delivered using intensity‐modulation, cone‐beam CT‐based image guidance and a robotic treatment couch. Clinical signs improved in all cases. Nineteen dogs had CT scans 3‐4 months post‐SRT and all had partial or complete tumour response. Minimal acute toxicities were detected. Clinically significant late toxicities included oronasal or nasocutaneous fistulas (N = 3) and biopsy‐confirmed fungal rhinitis with no evidence of tumour progression (N = 2). The median progression‐free survival (PFS) was 354 days, with 49% and 39% progression‐free at 1 and 2 years post‐SRT, respectively. The median survival time (ST) was 586 days, with 69% and 22% alive 1 and 2 years post‐SRT, respectively. Neither the clinical parameters evaluated (modified Adams’ stage, histopathology, presence of intracranial extension of the tumour) nor dosimetric data were predictive for PFS or ST. This SRT protocol appears to be well tolerated, and PFI and ST are comparable or superior to those reported in other definitive‐intent radiotherapy protocols.     

Alternating carboplatin and doxorubicin as adjunctive chemotherapy to amputation or limb-sparing surgery in the treatment of appendicular osteosarcoma in dogs

Thirty-two dogs with appendicular osteosarcoma treated by amputation or limb sparing had adjuvant chemotherapy of alternating doses of carboplatin (300 mg/m2 IV) and doxorubicin (30 mg/m2 IV) every 21 days for a total of 3 cycles. Efficacy, toxicity, and previously identified prognostic factors for osteosarcoma were evaluated. The median progression free survival was 227 days (range 180-274), and the median overall survival was 320 days (range 153-487). The 1-year survival rate was 48%, and the 2-year survival rate was 18%. Age, sex, surgical procedure, and alkaline phosphatase activity above the reference ranges were not prognostic for survival. There was minimal toxicity associated with the chemotherapy. This protocol could be useful for the adjuvant treatment of appendicular osteosarcoma of dogs.     

Samarium Sm 153 lexidronam for the palliative treatment of dogs with primary bone tumors: 35 cases (1999-2005)

OBJECTIVE: To evaluate survival times and palliative effects associated with the use of samarium Sm 153 lexidronam in dogs with primary bone tumors. DESIGN: Retrospective case series. ANIMALS: 35 dogs with primary appendicular (n = 32) or axial (3) bone tumors. PROCEDURES: 1 to 4 doses of samarium Sm 153 lexidronam were administered at a rate of 37 MBq/kg (16.8 MBq/lb), IV. Response to treatment, measured by lameness improvement, and survival time were determined. RESULTS: Of the 32 dogs with appendicular tumors, 20 (63%) had an improvement in the severity of lameness 2 weeks after administration of the first dose of radioactive samarium, 8 (25%) had no change in the severity of lameness, and 4 (12%) had a worsening. Overall median survival time was 100 days, with 3 dogs (8.6%) alive after 1 year. Median survival time for the 32 dogs with appendicular tumors was 93 days, with 3 (9.4%) alive after 1 year. This was not significantly different from the median survival time of 134 days for a historical cohort of 162 dogs with appendicular osteosarcoma that underwent amputation as the only treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samarium Sm 153 lexidronam may be useful in the palliation of pain in dogs with primary bone tumors that are not candidates for curative-intent treatment.     

Safety and feasibility of stereotactic radiotherapy using computed portal radiography for canine intracranial tumors

Stereotactic radiotherapy is a highly conformal treatment option for intracranial and extracranial malignancies. Stereotactic radiotherapy utilizes specialized equipment specifically designed to avoid normal tissue while delivering ablative treatments with submillimeter precision and accuracy. Linear accelerator based stereotactic radiotherapy incorporates on‐board image guidance utilizing cone beam computed tomography (CT). Many institutions lack the ability to provide image guidance with cone beam CT but delivery of highly conformal treatments with submillimeter precision and accuracy is still feasible. The purpose of this retrospective, pilot study was to describe clinical outcomes for a group of dogs with neurological disease that were treated with an stereotactic radiotherapy technique utilizing intensity modulated radiation therapy, megavoltage computed portal radiography, a bite plate, thermoplastic mold, and mask based positioning system. Twelve dogs with neurological clinical signs were included. The diagnosis of intracranial tumor was made based on advanced imaging (12/12) and confirmed via histopathology (3/12). Twelve courses of stereotactic radiotherapy, utilizing three fractions of 8.0 Gy, were delivered on alternating days. Self‐resolving neurological deterioration was observed in two patients during stereotactic radiotherapy. Neurological progression free interval and median survival time were 273 days (range: 16–692 days) and 361 days (range: 25–862 days). Stereotactic radiotherapy using computed portal radiography may be a safe treatment option for dogs with intracranial tumors.     

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.     

Bone allografts and adjuvant cisplatin for the treatment of canine appendicular osteosarcoma in 18 dogs

The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.     

Osteosarcoma in cats: 22 cases (1974-1984)

Osteosarcoma was diagnosed in 22 cats. Diagnosis was based on results of physical, radiographic, and histologic findings. Fifteen tumors arose from the appendicular skeleton, 4 from the skull, 2 from the pelvis, and 1 from a rib. Radiography revealed that in 14 of 15 cats (93%) with appendicular tumors, the lesion was metaphyseal, primarily lytic, with a "moth-eaten" appearance; absence and presence of periosteal new bone formation were associated with the tumors in 12 and 3 cats, respectively. The remaining 7 cats had axial tumors that were characterized by the presence of periosteal new bone formation in addition to bony lysis. Of the 15 cats with appendicular tumors, 12 were treated by amputation and 3 were euthanatized at the time of diagnosis. Of the cats undergoing amputation for treatment of their appendicular tumors, 6 cats were still alive 64 months after surgery (range, 13 to 64 months); the median survival time of the 5 cats (1 cat was lost to follow-up evaluation) that died was 49.2 months (range, 1 to 122 months). Four of 12 cats (33%) survived greater than or equal to 5 years after diagnosis. Of the cats with axial tumors that were not euthanatized at the time of diagnosis (6 of 7), the median survival time was 5.5 months. Based on these findings, we concluded that cats with appendicular osteosarcoma have a better prognosis than those with axial osteosarcoma, and that amputation is a viable treatment for cats with appendicular osteosarcoma.     

Long‐term survival with stereotactic radiotherapy for imaging‐diagnosed pituitary tumors in dogs

Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging‐diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009–2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226–410 days [range 1–2134 days]). Thirty‐two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221–427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2–626 days]). Twenty‐nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P = 0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.     

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.     

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceral EOS in dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceral EOS.