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
Awarded By
Lumicell Diagnostics
Role
Principal Investigator
Start Date
End Date

A Prospective Observational Study of Intraoperative Angiography for Predicting Wound Complications in Irradiated Soft Tissue Sarcoma of the Extremities

Administered By
Orthopaedics
Awarded By
Piedmont Orthopedic Foundation
Role
Co-Principal Investigator
Start Date
End Date

SCH: Overcoming the Intraoperative Data Desert: Biophotonics, Advanced Sensing, and Control for Automated Surgery

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Phase 1 Study of X-PACT (X-ray Psoralen Activated Cancer Therapy)

Administered By
Orthopaedics
Awarded By
Immunolight, LLC
Role
Principal Investigator
Start Date
End Date

Publications:

Humeral Shaft Fracture With Placement of an Intramedullary Nail Through an Unrecognized Sarcoma.

CASE: A 72-year-old man underwent intramedullary nailing of a humeral diaphysis fracture with passage through an unrecognized pathologic fracture. Four months later, a biopsy of a soft-tissue mass in the arm revealed pleomorphic undifferentiated sarcoma. Only after local recurrence and forequarter amputation was the story of a pathologic fracture through undifferentiated pleomorphic sarcomas of bone clear. The patient developed metastatic disease and died after 2 years postoperatively. DISCUSSION: Orthopaedic surgeons should consider sarcoma when assessing patients with fractures of unknown etiology and an inappropriate mechanism because the placement of an intramedullary device through a sarcoma of bone has consequences.
Authors
Cullen, MM; Okwumabua, E; Flamant, EM; Ferlauto, HR; Brigman, BE; Eward, WC
MLA Citation
Cullen, Mark M., et al. “Humeral Shaft Fracture With Placement of an Intramedullary Nail Through an Unrecognized Sarcoma.J Am Acad Orthop Surg Glob Res Rev, vol. 5, no. 2, Feb. 2021. Pubmed, doi:10.5435/JAAOSGlobal-D-20-00142.
URI
https://scholars.duke.edu/individual/pub1474547
PMID
33620175
Source
pubmed
Published In
Journal of the American Academy of Orthopaedic Surgeons. Global Research & Reviews
Volume
5
Published Date
DOI
10.5435/JAAOSGlobal-D-20-00142

Urinary Pubic Symphysis Fistula Leads to Histopathologic Osteomyelitis in Prostate Cancer Survivors.

OBJECTIVE: To assess the histologic findings in the pubic bone resected during extirpative surgery for urinary pubic symphysis fistula (UPF). The concurrent presence of osteomyelitis and the need for bone resection at time of extirpative surgery for UPF has been debated. We hypothesized that UPF results in histopathologically confirmed osteomyelitis, underscoring the importance of bone resection at the time of surgery. METHODS: An IRB-approved retrospective review of all patients undergoing surgery for UPF from 2012 to 2019 was performed. Demographic data were recorded. A single pathologist performed histopathologic examination of bone tissue in each case. Logistic regression and Fisher exact test were used to assess association of osteomyelitis with clinical factors. RESULTS: We identified 36 patients who underwent major extirpative surgery for UPF with bone pathology available for review. Bone histopathology findings confirmed presence of osteomyelitis in the majority (n = 32, 88.9%). This was characterized as chronic osteomyelitis in 15 (41.7%), acute osteomyelitis only in 1 (2.8%) and combined chronic, and acute osteomyelitis in 16 (44.4%). Osteonecrosis was seen in 11 cases (33.6%). There was no correlation between presence of osteomyelitis and age, timing from radiotherapy to diagnosis of UPF, type of radiotherapy, or history of endoscopic bladder outlet procedures. CONCLUSION: Osteomyelitis is present on histology of the pubic bone resected during surgery for UPF in the majority of cases (88.9%). Osteonecrosis is also common. These findings underscore the critical importance of pubic bone resection at time of UPF surgery to adequately treat the diseased bone.
Authors
Kahokehr, AA; Boysen, WR; Schild, MH; Nosé, BD; Huang, J; Eward, W; Peterson, AC
MLA Citation
Kahokehr, Arman A., et al. “Urinary Pubic Symphysis Fistula Leads to Histopathologic Osteomyelitis in Prostate Cancer Survivors.Urology, vol. 148, Feb. 2021, pp. 297–301. Pubmed, doi:10.1016/j.urology.2020.07.038.
URI
https://scholars.duke.edu/individual/pub1453651
PMID
32763316
Source
pubmed
Published In
Urology
Volume
148
Published Date
Start Page
297
End Page
301
DOI
10.1016/j.urology.2020.07.038

Exploring the Diversity of the Marine Environment for New Anti-cancer Compounds

Marine ecosystems contain over 80% of the world’s biodiversity, and many of these organisms have evolved unique adaptations enabling survival in diverse and challenging environments. The biodiversity within the world’s oceans is a virtually untapped resource for the isolation and development of novel compounds, treatments, and solutions to combat human disease. In particular, while over half of our anti-cancer drugs are derived from natural sources, almost all of these are from terrestrial ecosystems. Yet, even from the limited analyses to date, a number of marine-derived anti-cancer compounds have been approved for clinical use, and several others are currently in clinical trials. Here, we review the current suite of marine-derived anti-cancer drugs, with a focus on how these compounds act upon the hallmarks of cancer. We highlight potential marine environments and species that could yield compounds with unique mechanisms. Continued exploration of marine environments, along with the characterization and screening of their inhabitants for unique bioactive chemicals, could prove fruitful in the hunt for novel anti-cancer therapies.
Authors
Dayanidhi, DL; Thomas, BC; Osterberg, JS; Vuong, M; Vargas, G; Kwartler, SK; Schmaltz, E; Dunphy-Daly, MM; Schultz, TF; Rittschof, D; Eward, WC; Roy, C; Somarelli, JA
MLA Citation
Dayanidhi, D. L., et al. “Exploring the Diversity of the Marine Environment for New Anti-cancer Compounds.” Frontiers in Marine Science, vol. 7, Jan. 2021. Scopus, doi:10.3389/fmars.2020.614766.
URI
https://scholars.duke.edu/individual/pub1472161
Source
scopus
Published In
Frontiers in Marine Science
Volume
7
Published Date
DOI
10.3389/fmars.2020.614766

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

BACKGROUND: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. METHODS: To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. RESULTS: Coupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. CONCLUSIONS: These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.
Authors
Somarelli, JA; Rupprecht, G; Altunel, E; Flamant, EM; Rao, S; Sivaraj, D; Lazarides, AL; Hoskinson, SM; Sheth, MU; Cheng, S; Kim, SY; Ware, KE; Agarwal, A; Cullen, MM; Selmic, LE; Everitt, JI; McCall, SJ; Eward, C; Eward, WC; Hsu, DS
MLA Citation
Somarelli, Jason A., et al. “A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.Cancers (Basel), vol. 12, no. 11, Nov. 2020. Pubmed, doi:10.3390/cancers12113335.
URI
https://scholars.duke.edu/individual/pub1465119
PMID
33187254
Source
pubmed
Published In
Cancers
Volume
12
Published Date
DOI
10.3390/cancers12113335

Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database.

BACKGROUND: Historically, amputation was the primary surgical treatment for osteosarcoma of the extremities; however, with advancements in surgical techniques and chemotherapies limb salvage has replaced amputation as the dominant treatment paradigm. This study assessed the type of surgical resection chosen for osteosarcoma patients in the twenty-first century. METHODS: Utilizing the largest registry of primary osteosarcoma, the National Cancer Database (NCDB), we retrospectively analyzed patients with high grade osteosarcoma of the extremities from 2004 through 2015. Differences between patients undergoing amputation and patients undergoing limb salvage are described. Unadjusted five-year overall survival between patients who received limb salvage and amputation was assessed utilizing Kaplan Meier curves. A multivariate Cox proportional hazard model and propensity matched analysis was used to determine the variables independently correlated with survival. RESULTS: From a total of 2442 patients, 1855 underwent limb salvage and 587 underwent amputation. Patients undergoing amputation were more likely to be older, male, uninsured, and live in zip codes associated with lower income. Patients undergoing amputation were also more likely to have larger tumors, more comorbid conditions, and metastatic disease at presentation. After controlling for confounders, limb salvage was associated with a significant survival benefit over amputation (HR: 0.70; p < 0.001). Although this may well reflect underlying biases impacting choice of treatment, this survival benefit remained significant after propensity matched analysis of all significantly different independent variables (HR: 0.71; p < 0.01). CONCLUSION: Among patients in the NCDB, amputation for osteosarcoma is associated with advanced age, advanced stage, larger tumors, greater comorbidities, and lower income. Limb salvage is associated with a significant survival benefit, even when controlling for significant confounding variables and differences between cohorts.
Authors
Evans, DR; Lazarides, AL; Visgauss, JD; Somarelli, JA; Blazer, DG; Brigman, BE; Eward, WC
MLA Citation
Evans, Daniel R., et al. “Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database.Bmc Cancer, vol. 20, no. 1, Oct. 2020, p. 995. Pubmed, doi:10.1186/s12885-020-07502-z.
URI
https://scholars.duke.edu/individual/pub1462949
PMID
33054722
Source
pubmed
Published In
Bmc Cancer
Volume
20
Published Date
Start Page
995
DOI
10.1186/s12885-020-07502-z