Radiotherapy prior to cortical allograft limb sparing in dogs with osteosarcoma: A dose response assay

Thrall, Donald E.; Withrow, Stephen J.; Powers, Barbara E.; Straw, Rodney C.; Page, Rodney L.; Heidner, Greta L.; Richardson, Daniel C.; Bissonnette, Kevin; Betts, C. W.; DeYoung, David J.; Wrigley, Robert; Sim, Dalice; Richter, Swetlana; LaRue, Susan M.; Gillette, Edward L.

doi:10.1016/0360-3016(90)90308-7

Cited by 42 publications

(34 citation statements)

References 17 publications

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“…For example, while the soft tissue component of appendicular osteosarcomas may shrink after irradiation, it would be uncommon for the bony matrix of these tumours to completely regress. In fact, increased tumour mineral density is common after irradiation of canine appendicular osteosarcoma, and that phenomenon has even been associated with improved clinical outcomes . This pattern of incomplete bone tumour regression seems logical, since at a cellular level, even with radiation‐induced neoplastic cell death, resorption of the tumour's extracellular matrix may be incomplete.…”

Section: Discussionmentioning

confidence: 99%

Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases

Sweet

Nolan

Yoshikawa

et al. 2019

Vet Comparative Oncology

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Radiotherapy is often considered in the management of canine multilobular osteochondrosarcoma (MLO), but its efficacy against bulky MLO tumours is poorly described. This retrospective case series describes the clinical outcomes of pet dogs with MLO treated with a stereotactic radiation therapy (SRT) prescription of 30 Gy in three consecutive daily 10 Gy fractions. Dogs with an imaging (via computed tomography [CT] scan) and/or pathologic diagnosis of MLO were included. Patient demographics, tumour characteristics, radiation plan dosimetry, toxicity and outcome data were obtained retrospectively from the records. The median progression‐free survival time (MPFST) and median overall survival time (MST) were calculated using a LOGLOG test. Eight dogs were included. None had evidence of metastasis at the time of SRT. Clinical signs associated with the MLO included a mass noted by owner, stertor, vestibular signs, exophthalmos and abnormal mentation. Of the five dogs that had CT scans performed 3 to 9 months after SRT, tumour volume decreased by 26% to 87% in four dogs and increased by 32% in one dog. Late radiation toxicity was documented in three dogs (VRTOG Grade 1 skin and/or ocular, n = 2; Grade 3 central nervous system, n = 1). Confirmed local disease progression (n = 3; two were treated with a second course of SRT) and suspected pulmonary metastasis (n = 2) occurred 90 to 315 days after SRT. The MPFST was 223 days (interquartile range [IQR]: 144.5‐276.5 days). The MST was 329 days (IQR: 241.5‐408 days). This protocol was well‐tolerated, but the duration of response was short‐lived.

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Section: Discussionmentioning

confidence: 99%

Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases

Sweet

Nolan

Yoshikawa

et al. 2019

Vet Comparative Oncology

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“…48 The percent tumor necrosis was the strongest predictor of local tumor control. Dogs with a high (greater than 75%) percent tumor necrosis had fewer local recurrences than those with less than 75% tumor necrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Alternately, it was easier to perfuse the radius and ulna evenly versus the proximal humerus with chemotherapy. In a previous canine osteosarcoma study using preoperative radiation alone (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52), the percent tumor necrosis did not vary with the dose nor did it predict local r e c u r r e n~e .~~ This may have been the result of the fact that the radiation dose in the previous study was generally higher than in this trial (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). The high-dose groups in the previous study may have exceeded the minimal dose required to achieve 75% tumor necrosis.…”

Section: Discussionmentioning

confidence: 99%

Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma

Withrow

Thrall

Straw

et al. 1993

Cancer

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“…In the late 19th century, William Coley utilized bacterial immunotherapy to treat sarcomas . Surgical site infections after limb‐salvage surgery are associated with improved survival in both canine and human OS patients . Additionally, a murine study demonstrated induction of anti‐OS activity in tumour‐bearing mice with concurrent bacterial osteomyelitis, and demonstrated that one of the key players in the anti‐tumour response is the macrophage .…”

Section: Introductionmentioning

confidence: 99%

Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF‐β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma

Tuohy

Somarelli

Borst

et al. 2019

Vet Comparative Oncology

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Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti‐tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co‐cultured with osteosarcoma and S. aureus exhibited increased IFN‐γ, TNF‐α and IL‐12p70 cytokine secretion, decreased TGF‐β cytokine secretion and increased mRNA expression of TNF‐α when compared with macrophages co‐cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN‐γ and TNF‐α cytokine secretion, decreased TGF‐β cytokine secretion, increased mRNA expression of TNF‐α and increased surface receptor expression of CD80 when co‐cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma‐induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti‐osteosarcoma macrophage response.

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Radiotherapy prior to cortical allograft limb sparing in dogs with osteosarcoma: A dose response assay

Cited by 42 publications

References 17 publications

Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases

Stereotactic radiation therapy for canine multilobular osteochondrosarcoma: Eight cases

Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma

Immune dysregulation and osteosarcoma: Staphylococcus aureus downregulates TGF‐β and heightens the inflammatory signature in human and canine macrophages suppressed by osteosarcoma

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