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

Publications:

Extirpative Cultures Reveal Infectious Pubic Bone Osteomyelitis in Prostate Cancer Survivors With Urinary-Pubic Symphysis Fistulae (UPF).

OBJECTIVE: To examine the infectious features of patients with urinary pubic symphysis fistula (UPF) and their association with osteomyelitis. METHODS: We conducted a review of our quality improvement database for 36 patients with UPF undergoing bone resection and extirpative surgery from October 2012 to January 2019. An assessment of bone and urine cultures was carried out along with surgical, radiologic, and demographic data. We analyzed descriptive statistics and used Fisher Exact Tests and unpaired Welch t tests to assess for associations with positive bone cultures. RESULTS: In our cohort, 33 patients (91.7%) had positive bone cultures with the 3 most common organisms being candida (22.0%), enterococcus (18.0%), and pseudomonas (10.0%). There was a correlation between positive preoperative urine culture and positive bone culture (P <.01), with 63.0% of those with positive urine cultures growing the same organism on bone culture. CONCLUSION: In this series, 91.7% of patients undergoing extirpative surgery for UPF at our institution have positive bone cultures at time of pubic bone debridement. Additionally, we demonstrate a statistically significant correlation between positive urine cultures and positive bone cultures in these patients. This supports the need for a multidisciplinary approach including infectious disease, orthopedic surgery and reconstructive urology in order to address this complex clinical condition.
Authors
Nosé, BD; Boysen, WR; Kahokehr, AA; Inouye, BM; Eward, WC; Hendershot, EF; Peterson, AC
MLA Citation
Nosé, Brent D., et al. “Extirpative Cultures Reveal Infectious Pubic Bone Osteomyelitis in Prostate Cancer Survivors With Urinary-Pubic Symphysis Fistulae (UPF).Urology, vol. 142, Aug. 2020, pp. 221–25. Pubmed, doi:10.1016/j.urology.2020.04.095.
URI
https://scholars.duke.edu/individual/pub1441179
PMID
32389815
Source
pubmed
Published In
Urology
Volume
142
Published Date
Start Page
221
End Page
225
DOI
10.1016/j.urology.2020.04.095

Defining a textbook surgical outcome for patients undergoing surgical resection of intermediate and high-grade soft tissue sarcomas of the extremities.

BACKGROUND: Quality measures for the surgical management soft tissue sarcoma of the extremity are limited. The purpose of this study was to define a textbook surgical outcome (TO) for soft tissue sarcoma of the extremities (STS-E) and to examine its associations with hospital volume and overall survival. METHODS: All patients in the National Cancer Database undergoing resection of primary STS-E between 2004 and 2015 were identified. The primary outcome was a TO, defined as: hospital length of stay (LOS) <75th percentile, survival >90 days from the date of surgery, no readmission within 30 days of discharge, and negative surgical margins (R0 resection). RESULTS: Overall, 7658 patients met criteria for inclusion; a TO was achieved in 4291 (56%) patients. Of patients who did not achieve TOs, 51.9% (n = 1748) had an extended LOS, and 47.3% (n = 1591) did not have negative margins. Older age, more medical comorbidities, and non-white or black race were independently associated with not receiving a TO (P = .034). With respect to tumor and treatment characteristics, larger tumor size, lower extremity location and higher grade were independently associated with not receiving a TO (P < .001). Hospital volume was not associated with a TO. TOs conferred a significant survival benefit (hazrds ratio = 0.71 [0.65-0.78], P < .001). A TO was associated with a 27.5% longer survival time (P < .001). CONCLUSIONS: This study defined a TO in intermediate and high-grade STS-E and demonstrated that this outcome measure is associated with overall survival. Facility volume was not associated with a TO.
Authors
Lazarides, AL; Cerullo, M; Moris, D; Brigman, BE; Blazer, DG; Eward, WC
MLA Citation
URI
https://scholars.duke.edu/individual/pub1452264
PMID
32691847
Source
pubmed
Published In
J Surg Oncol
Published Date
DOI
10.1002/jso.26087

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, such as sarcomas, access to patient samples is limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up <1% of all human cancers, sarcomas represent 15% of cancers in dogs. Because dogs have similar immune systems, an accelerated pace of cancer progression, and a shared environment with humans, studying pet dogs with cancer is ideal for bridging gaps between mouse models and human cancers. Here, we present our cross-species personalized medicine pipeline to identify new therapies for sarcomas. We explore this process through the focused study of a pet dog, Teddy, who presented with six synchronous leiomyosarcomas. Using our pipeline we identified proteasome inhibitors as a potential therapy for Teddy. Teddy was treated with bortezomib and showed a varied response across tumors. Whole exome sequencing revealed substantial genetic heterogeneity across Teddy's recurrent tumors and metastases, suggesting that intra-patient heterogeneity and tumoral adaptation were responsible for the heterogeneous clinical response. Ubiquitin proteomics coupled with exome sequencing revealed multiple candidate driver mutations in proteins related to the proteasome pathway. Together, our results demonstrate how the comparative study of canine sarcomas offers important insights into the development of personalized medicine approaches that can lead to new treatments for sarcomas in both humans and canines.
Authors
Rao, SR; Somarelli, JA; Altunel, E; Selmic, LE; Byrum, M; Sheth, MU; Cheng, S; Ware, KE; Kim, SY; Prinz, JA; Devos, N; Corcoran, DL; Moseley, A; Soderblom, E; Hsu, SD; Eward, WC
URI
https://scholars.duke.edu/individual/pub1434058
PMID
32117764
Source
pubmed
Published In
Frontiers in Oncology
Volume
10
Published Date
Start Page
117
DOI
10.3389/fonc.2020.00117

Does facility volume influence survival in patients with primary malignant bone tumors of the vertebral column? A comparative cohort study.

BACKGROUND CONTEXT: Facility volume has been correlated with survival in many cancers. This relationship has not been established in primary malignant bone tumors of the vertebral column (BTVC). PURPOSE: To investigate whether facility patient volume is associated with overall survival in patients with primary malignant BTVCs. STUDY DESIGN: Retrospective comparative cohort. PATIENT SAMPLE: Adult patients with chordomas, chondrosarcomas, or osteosarcomas of the mobile spine. OUTCOME MEASURES: Five-year survival. METHODS: We retrospectively analyzed 733 patients with primary malignant BTVCs in the national cancer database from 2004 through 2015. Univariate and multivariate analyses were used to correlate specific outcome measures with facility volume. Volume was stratified based on cumulative martingale residuals to determine the inflection point of negative to positive impact on survival based on the patient cohort. Long-term survival was compared between patients treated at high and low volume using the Kaplan-Meier method. Only patients with malignant primary tumors were considered eligible for inclusion; patients with incomplete treatment data or benign tumors were excluded. RESULTS: Patients treated at high-volume centers (HVCs) were younger (p=.0003) and more likely to be insured (p<.0001). There were no significant differences in tumor characteristics. Patients treated at high-volume facilities had improved 5-year survival of 71% versus 58% at low-volume centers (p<.0001). Patients treated at HVCs were more likely to receive surgical treatment (91% vs. 80%, p<.0001); if surgery was performed, they were more likely to undergo an en bloc resection (48% vs. 30%, p<.0001). However, there were no differences in margin status or utilization of radiotherapy or chemotherapy between HVCs and low-volume centers. In a multivariate analysis, facility volume was independently associated with improved survival overall (HR 0.75 [0.58-0.97], p=.03). CONCLUSIONS: Primary malignant BTVCs are rare, even for HVCs. Despite this, patient survival was significantly improved when treatment was performed at HVCs.
Authors
Lazarides, AL; Kerr, DL; Dial, BL; Steele, JR; Lane, WO; Blazer, DG; Brigman, BE; Mendoza-Lattes, S; Erickson, MM; Eward, WC
MLA Citation
Lazarides, Alexander L., et al. “Does facility volume influence survival in patients with primary malignant bone tumors of the vertebral column? A comparative cohort study.Spine J, vol. 20, no. 7, July 2020, pp. 1106–13. Pubmed, doi:10.1016/j.spinee.2020.02.020.
URI
https://scholars.duke.edu/individual/pub1433959
PMID
32145357
Source
pubmed
Published In
Spine J
Volume
20
Published Date
Start Page
1106
End Page
1113
DOI
10.1016/j.spinee.2020.02.020

Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma.

Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an established anthelminthic agent, as a niclosamide stearate prodrug therapeutic (NSPT). We sought to improve the low and inefficient clinical bioavailability of oral dosing, especially for the relatively hydrophobic classes of anticancer drugs. Nanoparticles were fabricated by rapid solvent shifting and verified using dynamic light scattering and UV-vis spectrophotometry. NSPT efficacy was then studied in vitro for cell viability, cell proliferation, and intracellular signaling by Western blot analysis; ex vivo pulmonary metastatic assay model; and in vivo pharmacokinetic and lung mouse metastatic model of osteosarcoma. NSPT formulation stabilizes niclosamide stearate against hydrolysis and delays enzymolysis; increases circulation in vivo with t1/2 approximately 5 hours; reduces cell viability and cell proliferation in human and canine osteosarcoma cells in vitro at 0.2-2 μmol/L IC50; inhibits recognized growth pathways and induces apoptosis at 20 μmol/L; eliminates metastatic lesions in the ex vivo lung metastatic model; and when injected intravenously at 50 mg/kg weekly, it prevents metastatic spread in the lungs in a mouse model of osteosarcoma over 30 days. In conclusion, niclosamide was optimized for preclinical drug delivery as a unique prodrug nanoparticle injected intravenously at 50 mg/kg (1.9 mmol/L). This increased bioavailability of niclosamide in the blood stream prevented metastatic disease in the mouse. This chemotherapeutic strategy is now ready for canine trials, and if successful, will be targeted for human trials in patients with osteosarcoma.
Authors
Reddy, GB; Kerr, DL; Spasojevic, I; Tovmasyan, A; Hsu, DS; Brigman, BE; Somarelli, JA; Needham, D; Eward, WC
MLA Citation
Reddy, Gireesh B., et al. “Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma.Mol Cancer Ther, vol. 19, no. 7, July 2020, pp. 1448–61. Pubmed, doi:10.1158/1535-7163.MCT-19-0689.
URI
https://scholars.duke.edu/individual/pub1439712
PMID
32371588
Source
pubmed
Published In
Mol Cancer Ther
Volume
19
Published Date
Start Page
1448
End Page
1461
DOI
10.1158/1535-7163.MCT-19-0689