William Eward

Overview:

I am an Orthopaedic Oncologist, with dual clinical degrees (MD and DVM).  I treat complex sarcomas in people and animals.  My laboratory studies comparative oncology - discoveries we can make about cancer by analyses across different species.

Positions:

Associate Professor of Orthopaedic Surgery

Orthopaedics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2006

University of Vermont College of Medicine

Grants:

Bortezomib: A novel treatment to improve outcomes in dogs with osteosarcoma

Administered By
Orthopaedics
Awarded By
Orthopaedic Research and Education Foundation
Role
Co-Principal Investigator
Start Date
End Date

Intraoperative detection and ablation of microscopic residual cancer in the tumor bed

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

Publications:

The Therapeutic Benefit of Radiotherapy for Chordoma Patients with Positive Surgical Margins

Authors
Dial, BL; Kerr, DL; Lazarides, AL; Catanzano, AA; Green, CL; Blazer, DG; Goodwin, R; Brigman, B; Eward, WC; Kirsch, D; Mendoza-Lattes, S
URI
https://scholars.duke.edu/individual/pub1409824
Source
ssrn

Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population.

Osteosarcoma, a malignant primary bone tumor most commonly diagnosed in children and adolescents, has a poorly understood genetic etiology. Genome-wide association studies (GWAS) and candidate-gene analyses have identified putative risk variants in subjects of European ancestry. However, despite higher incidence among African-American and Hispanic children, little is known regarding common heritable variation that contributes to osteosarcoma incidence and clinical presentation across racial/ethnic groups. In a multi-ethnic sample of non-Hispanic white, Hispanic, African-American and Asian/Pacific Islander children (537 cases, 2165 controls), we performed association analyses assessing previously-reported loci for osteosarcoma risk and metastasis, including meta-analysis across racial/ethnic groups. We also assessed a previously described association between genetic predisposition to longer leukocyte telomere length (LTL) and osteosarcoma risk in this independent multi-ethnic dataset. In our sample, we were unable to replicate previously-reported loci for osteosarcoma risk or metastasis detected in GWAS of European-ancestry individuals in either ethnicity-stratified analyses or meta-analysis across ethnic groups. Our analyses did confirm that genetic predisposition to longer LTL is a risk factor for osteosarcoma (ORmeta: 1.22; 95% CI: 1.09-1.36; P = 3.8 × 10-4), and the strongest effect was seen in Hispanic subjects (OR: 1.32; 95% CI: 1.12-1.54, P = 6.2 × 10-4). Our findings shed light on the replicability of osteosarcoma risk loci across ethnicities and motivate further characterization of these genetic factors in diverse clinical cohorts.
Authors
Zhang, C; Hansen, HM; Semmes, EC; Gonzalez-Maya, J; Morimoto, L; Wei, Q; Eward, WC; DeWitt, SB; Hurst, JH; Metayer, C; de Smith, AJ; Wiemels, JL; Walsh, KM
MLA Citation
Zhang, Chenan, et al. “Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population..” Bone, vol. 130, Jan. 2020. Pubmed, doi:10.1016/j.bone.2019.115070.
URI
https://scholars.duke.edu/individual/pub1411824
PMID
31525475
Source
pubmed
Published In
Bone
Volume
130
Published Date
Start Page
115070
DOI
10.1016/j.bone.2019.115070

Bioengineering a Future Free of Marine Plastic Waste

© Copyright © 2019 Sheth, Kwartler, Schmaltz, Hoskinson, Martz, Dunphy-Daly, Schultz, Read, Eward and Somarelli. Plastic waste has reached epidemic proportions worldwide, and the production of plastic continues to rise steadily. Plastic represents a diverse array of commonly used synthetic polymers that are extremely useful as durable, economically beneficial alternatives to other materials; however, despite the wide-ranging utility of plastic, the increasing accumulation of plastic waste in the environment has had numerous detrimental impacts. In particular, plastic marine debris can transport invasive species, entangle marine organisms, and cause toxic chemical bioaccumulation in the marine food web. The negative impacts of plastic waste have motivated research on new ways to reduce and eliminate plastic. One unique approach to tackle the plastic waste problem is to turn to nature’s solutions for degrading polymers by leveraging the biology of naturally occurring organisms to degrade plastic. Advances in metagenomics, next generation sequencing, and bioengineering have provided new insights and new opportunities to identify and optimize organisms for use in plastic bioremediation. In this review, we discuss the plastic waste problem and possible solutions, with a focus on potential mechanisms for plastic bioremediation. We pinpoint two key habitats to identify plastic-biodegrading organisms: (1) habitats with distinct enrichment of plastic waste, such as those near processing or disposal sites, and (2) habitats with naturally occurring polymers, such as cutin, lignin, and wax. Finally, we identify directions of future research for the isolation and optimization of these methods for widespread bioremediation applications.
Authors
Sheth, MU; Kwartler, SK; Schmaltz, ER; Hoskinson, SM; Martz, EJ; Dunphy-Daly, MM; Schultz, TF; Read, AJ; Eward, WC; Somarelli, JA
MLA Citation
Sheth, M. U., et al. “Bioengineering a Future Free of Marine Plastic Waste.” Frontiers in Marine Science, vol. 6, Oct. 2019. Scopus, doi:10.3389/fmars.2019.00624.
URI
https://scholars.duke.edu/individual/pub1416756
Source
scopus
Published In
Frontiers in Marine Science
Volume
6
Published Date
DOI
10.3389/fmars.2019.00624

Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study.

Background: Although chondrosarcomas (CS) are mostly considered radioresistant, advancements in radiotherapy have brought attention to its use in these patients. Using the largest registry of primary bone tumors, the National Cancer Database (NCDB), we sought to better characterize the current use of radiotherapy in CS patients and identify any potential survival benefit with higher radiation doses and advanced radiation therapies. Methods: We retrospectively analyzed CS patients in the NCDB from 2004 to 2015 who underwent radiotherapy. The Kaplan-Meier method with statistical comparisons was used to identify which individual variables related to dosage and delivery modality were associated with improved 5-year survival rates. Multivariate proportional hazards analyses were performed to determine independent predictors of survival. Results: Of 5,427 patients with a histologic diagnosis of chondrosarcoma, 680 received a form of radiation therapy (13%). The multivariate proportional hazards analysis controlling for various patient, tumor, and treatment variables, including RT dose and modality, demonstrated that while overall radiation therapy (RT) was not associated with improved survival (HR 0.96, 95% CI 0.76-1.20), when examining just the patient cohort with positive surgical margins, RT trended towards improved survival (HR 0.81, 95% CI 0.58-1.13). When comparing advanced and conventional RT modalities, advanced RT was associated with significantly decreased mortality (HR 0.55, 95% CI 0.38-0.80). However, advanced modality and high-dose RT both trended only toward improved survival compared to patients who did not receive any RT (HR 0.74, 95% CI 0.52-1.06 and HR 0.93, 95% CI 0.71-1.21, respectively). Conclusions: Despite the suggested radioresistance of CS, modern radiotherapies may present a treatment option for certain patients. Our results support a role for high-dose, advanced radiation therapies in selected high-risk CS patients with tumors in surgically challenging locations or unplanned positive margins. While there is an associated survival rate benefit, further, prospective studies are needed for validation.
Authors
Catanzano, AA; Kerr, DL; Lazarides, AL; Dial, BL; Lane, WO; Blazer, DG; Larrier, NA; Kirsch, DG; Brigman, BE; Eward, WC
MLA Citation
Catanzano, Anthony A., et al. “Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study..” Sarcoma, vol. 2019, 2019. Pubmed, doi:10.1155/2019/4878512.
URI
https://scholars.duke.edu/individual/pub1418046
PMID
31736653
Source
pubmed
Published In
Sarcoma
Volume
2019
Published Date
Start Page
4878512
DOI
10.1155/2019/4878512

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

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.
Authors
Tuohy, JL; Somarelli, JA; Borst, LB; Eward, WC; Lascelles, BDX; Fogle, JE
URI
https://scholars.duke.edu/individual/pub1404318
PMID
31420936
Source
pubmed
Published In
Vet Comp Oncol
Published Date
DOI
10.1111/vco.12529