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:
Frank H. Bassett III, M. D. Associate Professor of Orthopaedic Surgery
Orthopaedic Surgery
School of Medicine
Associate Professor of Orthopaedic Surgery
Orthopaedic Surgery
School of Medicine
Associate Professor of Pathology
Pathology
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:
Engineered imaging nanoparticles for real-time detection of cancer in the tumor bed
Administered By
Orthopaedic Surgery
Awarded By
Lumicell Diagnostics
Role
Investigator
Start Date
End Date
Bortezomib: A novel treatment to improve outcomes in dogs with osteosarcoma
Administered By
Orthopaedic Surgery
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
Orthopaedic Surgery
Awarded By
Lumicell Diagnostics
Role
Principal Investigator
Start Date
End Date
Intraoperative detection and ablation of microscopic residual cancer in the tumor bed
Administered By
Orthopaedic Surgery
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
Orthopaedic Surgery
Awarded By
Piedmont Orthopedic Foundation
Role
Co-Principal Investigator
Start Date
End Date
Publications:
Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.
ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a primary mouse model of soft tissue sarcoma and showed that Atrx-deleted tumors were more sensitive to radiation therapy and to oncolytic herpesvirus. In the absence of Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. Our work also showed that Atrx deletion resulted in downregulation of the CGAS/STING signaling pathway at multiple points in the pathway and was not driven by mutations or transcriptional downregulation of the CGAS/STING pathway components. We found that both human and mouse models of Atrx-deleted sarcoma had a reduced adaptive immune response, markedly impaired CGAS/STING signaling, and increased sensitivity to TVEC, an oncolytic herpesvirus that is currently FDA approved for the treatment of aggressive melanomas. Translation of these results to patients with ATRX-mutant cancers could enable genomically guided cancer therapy approaches to improve patient outcomes.
Authors
Floyd, W; Pierpoint, M; Su, C; Patel, R; Luo, L; Deland, K; Wisdom, AJ; Zhu, D; Ma, Y; DeWitt, SB; Williams, NT; Lazarides, AL; Somarelli, JA; Corcoran, DL; Eward, WC; Cardona, DM; Kirsch, DG
MLA Citation
Floyd, Warren, et al. “Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.” J Clin Invest, vol. 133, no. 13, July 2023. Pubmed, doi:10.1172/JCI149310.
URI
https://scholars.duke.edu/individual/pub1578433
PMID
37200088
Source
pubmed
Published In
J Clin Invest
Volume
133
Published Date
DOI
10.1172/JCI149310
Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.
BACKGROUND: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables. METHODS: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS). RESULTS: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS. CONCLUSIONS: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.
Authors
Lazarides, AL; Abar, B; Leckey, B; Martin, JT; Kliassov, EG; Brigman, BE; Eward, WC; Cardona, DM; Visgauss, JD
MLA Citation
Lazarides, Alexander L., et al. “Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.” Bmc Cancer, vol. 23, no. 1, June 2023, p. 579. Pubmed, doi:10.1186/s12885-023-11022-x.
URI
https://scholars.duke.edu/individual/pub1586263
PMID
37353743
Source
pubmed
Published In
Bmc Cancer
Volume
23
Published Date
Start Page
579
DOI
10.1186/s12885-023-11022-x
Regional anesthesia is associated with improved metastasis free survival after surgical resection of bone sarcomas.
There is increasing evidence that perioperative factors, including type of anesthesia, may be an important consideration regarding oncological disease progression. Previous studies have suggested that regional anesthesia can improve oncological outcomes by reducing the surgical stress response that occurs during tumor resection surgery and that may promote metastatic progression. The purpose of this study is to provide the first robust investigation of the impact of adding regional anesthesia to general anesthesia on oncological outcomes following sarcoma resection. One hundred patients with bone sarcoma were retrospectively analyzed in this study. After adjusting for confounding variables such as age and grade of the tumor, patients with bone sarcoma receiving regional anesthesia in addition to general anesthesia during resection had improved metastasis free survival (multivariate hazard ratio of 0.47 and p = 0.034). Future studies are needed to confer the beneficial effect of regional anesthesia, and to further investigate the potential mechanism. Clinical significance: The results from this study provide evidence that regional anesthesia may be advantageous in the setting of bone sarcoma resection surgery, reducing pain while also improving oncological outcomes and should be considered when clinically appropriate.
Authors
Abar, B; Gao, J; Fletcher, AN; Sachs, E; Wong, AH; Lazarides, AL; Okafor, C; Brigman, BE; Eward, WC; Jung, S-H; Kumar, AH; Visgauss, JD
MLA Citation
Abar, Bijan, et al. “Regional anesthesia is associated with improved metastasis free survival after surgical resection of bone sarcomas.” J Orthop Res, May 2023. Pubmed, doi:10.1002/jor.25597.
URI
https://scholars.duke.edu/individual/pub1575442
PMID
37151123
Source
pubmed
Published In
J Orthop Res
Published Date
DOI
10.1002/jor.25597
Giant cell tumor of bone in the pediatric population: a retrospective study highlighting cases of metaphyseal only location and increased local recurrence rates in skeletally immature patients.
OBJECTIVE: To describe the presentation of giant cell tumors (GCT) of the bone in the pediatric population to (1) improve the differential diagnosis of pediatric bone tumors and (2) identify the origin of GCT. Understanding the origin of bone tumors assists in establishing appropriate diagnoses and recommending treatment options. This is particularly important in children, where evaluating the need for invasive procedures is balanced with the desire to avoid overtreatment. GCT have historically been considered epiphyseal lesions with potential metaphyseal extension. Therefore, GCT may be inappropriately excluded from the differential diagnosis of metaphyseal lesions in the skeletally immature. MATERIALS AND METHODS: We identified 14 patients from 1981 to 2021 at a single institution who had histologic confirmation of GCT and were less than 18 years old at diagnosis. Patient characteristics, tumor location, surgical treatment, and local recurrence rates were collected. RESULTS AND CONCLUSIONS: Ten (71%) patients were female. Eleven (78.6%) were epiphysiometaphyseal (1 epiphyseal, 4 metaphyseal, 6 epiphysiometaphyseal). Five patients had an open adjacent physis, of which three (60%) had tumors confined solely to the metaphysis. Of the five patients with open physis, four (80%) developed local recurrence while only one patient (11%) with a closed physis had local recurrence (p value = 0.0023). Our results illustrate that for the skeletally immature, GCT can (and in our results more commonly did) occur in the metaphyseal location. These findings suggest that GCT should be included in the differential diagnosis of primary metaphyseal-only lesions in the skeletally immature.
Authors
Tabarestani, TQ; Levine, N; Sachs, E; Scholl, A; Colglazier, R; French, R; Al-Rohil, R; Brigman, B; Eward, W; Visgauss, J
MLA Citation
Tabarestani, Troy Q., et al. “Giant cell tumor of bone in the pediatric population: a retrospective study highlighting cases of metaphyseal only location and increased local recurrence rates in skeletally immature patients.” Skeletal Radiol, May 2023. Pubmed, doi:10.1007/s00256-023-04359-8.
URI
https://scholars.duke.edu/individual/pub1575443
PMID
37154873
Source
pubmed
Published In
Skeletal Radiol
Published Date
DOI
10.1007/s00256-023-04359-8
Hydropneumodissection-Assisted Cryoablation of Recurrent Sarcoma Adjacent to the Sciatic Nerve as a Limb-Sparing Alternative to Hindquarter Amputation.
Authors
MLA Citation
Sag, Alan A., et al. “Hydropneumodissection-Assisted Cryoablation of Recurrent Sarcoma Adjacent to the Sciatic Nerve as a Limb-Sparing Alternative to Hindquarter Amputation.” J Vasc Interv Radiol, vol. 34, no. 5, May 2023, pp. 923-926.e1. Pubmed, doi:10.1016/j.jvir.2022.12.469.
URI
https://scholars.duke.edu/individual/pub1561049
PMID
36584809
Source
pubmed
Published In
J Vasc Interv Radiol
Volume
34
Published Date
Start Page
923
End Page
926.e1
DOI
10.1016/j.jvir.2022.12.469

Frank H. Bassett III, M. D. Associate Professor of Orthopaedic Surgery
Contact:
Box 3312 DUMC, Durham, NC 27710
Dept. of Orthopaedic Surgery, Durham, NC 27710