Improved Survival Associated With Postoperative Wound Infection in Dogs Treated With Limb-Salvage Surgery for Osteosarcoma

Lascelles, B. Duncan X.; Dernell, William S.; Correa, María T.; Lafferty, Mary; Devitt, Chad M.; Kuntz, Charles; Straw, Rodney C.; Withrow, Stephen J.

doi:10.1245/aso.2005.01.011

Cited by 123 publications

(158 citation statements)

References 62 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Similar findings have been detected in canine osteosarcoma studies, suggesting an immune response may inhibit osteosarcoma tumors in vivo [10]. The production of tumor-specific humoral and cellular immune responses to osteosarcoma has been previously recognized, prompting interest in the potential role of immunotherapy in osteosarcoma [11,12].…”

Section: Immunotherapysupporting

confidence: 76%

Current concepts on the surgical and medical management of osteosarcoma

Siegel

Pressey

2008

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Although advances have been made in both surgical and medical management of patients with osteosarcoma, the overall survival of patients with osteosarcoma has remained constant, with no substantial improvement in the past 15 years. Advances in imaging have had a substantial impact on surgical planning and staging. These advances have, in turn, had a major impact on the surgeon's ability to perform limb-sparing surgery. Surgical techniques have improved in terms of instrumentation, modularity of implants and availability. Limb salvage has proven to be an acceptable method of treatment both with respect to oncologic and functional outcome in those patients where a wide resection may be achieved. The use of massive allografts has been largely replaced with the use of modern oncologic endoprostheses. Biologic targets that will enable new therapies to have maximum effect on tumor cells while minimizing toxicity to the host tissues need to be identified.

show abstract

Section: Immunotherapysupporting

confidence: 76%

Current concepts on the surgical and medical management of osteosarcoma

Siegel

Pressey

2008

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

show abstract

“…Previously, nonspecific immune stimuli, such as spontaneous bacterial infections following limb sparing surgery (38,39) or liposome encapsulated muramyl tripeptides (L-MTP-PE) administered after amputation and platinum therapy have resulted in significant prolongation of metastasis-free interval (11.3 months vs. 7.6 months; control) and overall survival (14.4 months vs. 9.8 months; control) in dogs with osteosarcoma (37,38). Consequently, L-MTP-PE (mifamurtide; MEPACT) was evaluated in, and received approval for pediatric osteosarcoma in Europe in 2009.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma

Mason

Gnanandarajah

Engiles

et al. 2016

Clinical Cancer Research

148

126

View full text Add to dashboard Cite

Purpose: Recombinant Listeria vaccines induce tumor-specific T-cell responses that eliminate established tumors and prevent metastatic disease in murine cancer models. We used dogs with HER2/neu þ appendicular osteosarcoma, a well-recognized spontaneous model for pediatric osteosarcoma, to determine whether a highly attenuated, recombinant Listeria monocytogenes expressing a chimeric human HER2/neu fusion protein (ADXS31-164) could safely induce HER2/neu-specific immunity and prevent metastatic disease. Experimental Design: Eighteen dogs that underwent limb amputation or salvage surgery and adjuvant chemotherapy were enrolled in a phase I dose escalation clinical trial and received either 2 Â 10 8 , 5 Â 10 8 , 1 Â 10 9 , or 3.3 Â 10 9 CFU of ADXS31-164 intravenously every 3 weeks for 3 administrations.Results: Only low-grade, transient toxicities were observed. ADXS31-164 broke peripheral tolerance and induced antigenspecific IFNg responses against the intracellular domain of HER2/neu in 15 of 18 dogs within 6 months of treatment. Furthermore, ADXS31-164 reduced the incidence of metastatic disease and significantly increased duration of survival time and 1-, 2-, and 3-year survival rates when compared with a historical control group with HER2/neu þ appendicular osteosarcoma treated with amputation and chemotherapy alone.Conclusions: These findings demonstrate that ADXS31-164 administered in the setting of minimal residual disease can induce HER2/neu-specific immunity and may reduce the incidence of metastatic disease and prolong overall survival in a clinically relevant, spontaneous, large animal model of cancer. These findings, therefore, have important translational relevance for children with osteosarcoma and adults with other HER2/neu þ cancers.

show abstract

“…The sarcoma surgical literature has reported correlations between deep surgical infection and improved overall survival. In a study of 47 dogs with sarcoma, Lascelles et al found a correlation between survival and the clinical event of a deep surgical infection [11]. Additionally, a large study from the Royal Orthopaedic Hospital in Birmingham, England, showed a statistical (p=0.017) advantage to deep surgical infection in terms of long-term survival [12].…”

Section: Foundationsmentioning

confidence: 99%

Immunotherapy in Sarcoma: Future Horizons

et al. 2015

View full text Add to dashboard Cite

Immunologic approaches to cancer are over a century old. Over the years, the strategy has been fine-tuned from inciting infections in subjects to inhibiting negative regulatory signals from the innate immune system. Sarcomas are among the first tumors to be considered for immune interventions. From Coley's toxin to cytokine-based therapies to adoptive cell therapy, there have been numerous immunotherapeutic investigations in this patient population. A promising strategy includes adoptive T cell therapy which has been studied in small cohorts of synovial sarcoma, a subtype that is known to widely express the cancer testis antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal cell carcinoma demonstrate the utility and tremendous efficacy of immune checkpoint blockade with increased rates of durable responses compared to standard therapies. Responses in traditionally "non-immunogenic" tumors, such as lung and bladder cancers, provide ample rationale for the study of immune checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses in sarcomas, further research will help clarify optimal patient selection for future clinical trials and new combinatorial immunotherapeutic strategies.

show abstract

Improved Survival Associated With Postoperative Wound Infection in Dogs Treated With Limb-Salvage Surgery for Osteosarcoma

Abstract: In dogs with osteosarcoma treated with limb-salvage surgery, infection has a positive influence on survival, as does a smaller initial length of radius involved and lower body weight.

Cited by 123 publications

References 62 publications

Current concepts on the surgical and medical management of osteosarcoma

Current concepts on the surgical and medical management of osteosarcoma

Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma

Immunotherapy in Sarcoma: Future Horizons

Contact Info

Product

Resources

About