Brian Brigman

Positions:

Associate Professor of Orthopaedic Surgery

Orthopaedics
School of Medicine

Associate Professor of Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1994

University of North Carolina - Chapel Hill

Intern, Surgery

University of Nebraska, Lincoln

Resident, Orthopaedic Surgery

University of Nebraska, Lincoln

Fellow, Orthopaedic Oncology

Boston University

Grants:

Fresh Tissue Lab Agreement

Administered By
Orthopaedics
Awarded By
DePuy Synthes Companies
Role
Principal Investigator
Start Date
End Date

Protocol Number: 14-03-PATHOLHUM-02

Administered By
Orthopaedics
Awarded By
IlluminOss Medical, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

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

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

A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults.

OBJECTIVE: Lumbar punctures (LPs) are important for obtaining CSF in neurology studies but are associated with adverse events and feared by many patients. We determined adverse event rates and pain scores in patients prospectively enrolled in two cohort studies who underwent LPs using a standardized protocol and 25 g needle. METHODS: Eight hundred and nine LPs performed in 262 patients age ≥ 60 years in the MADCO-PC and INTUIT studies were analyzed. Medical records were monitored for LP-related adverse events, and patients were queried about subjective complaints. We analyzed adverse event rates, including headaches and pain scores. RESULTS: There were 22 adverse events among 809 LPs performed, a rate of 2.72% (95% CI 1.71-4.09%). Patient hospital stay did not increase due to adverse events. Four patients (0.49%) developed a post-lumbar puncture headache (PLPH). Twelve patients (1.48%) developed nausea, vasovagal responses, or headaches that did not meet PLPH criteria. Six patients (0.74%) reported lower back pain at the LP site not associated with muscular weakness or paresthesia. The median pain score was 1 [0, 3]; the mode was 0 out of 10. CONCLUSIONS: The LP protocol described herein may reduce adverse event rates and improve patient comfort in future studies.
Authors
Nobuhara, CK; Bullock, WM; Bunning, T; Colin, B; Cooter, M; Devinney, MJ; Ferrandino, MN; Gadsden, J; Garrigues, G; Habib, AS; Moretti, E; Moul, J; Ohlendorf, B; Sandler, A; Scheri, R; Sharma, B; Thomas, JP; Young, C; Mathew, JP; Berger, M; MADCO-PC and INTUIT Investigators Teams,
MLA Citation
Nobuhara, Chloe K., et al. “A protocol to reduce self-reported pain scores and adverse events following lumbar punctures in older adults.J Neurol, vol. 267, no. 7, July 2020, pp. 2002–06. Pubmed, doi:10.1007/s00415-020-09797-1.
URI
https://scholars.duke.edu/individual/pub1434663
PMID
32198714
Source
pubmed
Published In
J Neurol
Volume
267
Published Date
Start Page
2002
End Page
2006
DOI
10.1007/s00415-020-09797-1

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

The Role of Radiotherapy for Chordoma Patients Managed With Surgery: Analysis of the National Cancer Database.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine if adjuvant radiation therapy (RT) improves overall survival (OS) following surgical resection of chordomas. SUMMARY OF BACKGROUND DATA: The role of RT for the treatment of chordomas remains incompletely described. Previous studies have not found adjuvant RT to improve OS, but these studies did not group patients based on surgical margin status or radiation dose or modality. We used the National Cancer Database to investigate the role of RT in chordomas following surgical resection. METHODS: Patients were stratified based on surgical margin status (positive vs. negative). Utilizing the Kaplan-Meier method, OS was compared between treatment modalities (surgical resection alone, therapeutic RT alone, and surgical resection plus therapeutic RT). OS was subsequently compared between patients treated with palliative dose (<40 Gy), low dose (40-65 Gy), and high dose (>65 Gy) RT. Similarly, OS was compared between advanced RT modalities including proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and external beam radiation therapy (EBRT). A multivariable model was used to determine adjusted variables predictive of mortality. RESULTS: One thousand four hundred seventy eight chordoma patients were identified; skull base (n = 567), sacral (n = 551), and mobile spine (n = 360). Surgical resection and therapeutic adjuvant RT improved 5-year survival in patients with positive surgical margins (82% vs. 71%, P = 0.03). No clear survival benefit was observed with the addition of adjuvant RT in patients with negative surgical margins. High dose RT was associated with improved OS compared with palliative and low dose RT (P < 0.001). Advanced RT techniques and SRS were associated with improved OS compared with EBRT. In the multivariate analysis high dose advanced RT (>65 Gy) was superior to EBRT. CONCLUSION: Patients with positive surgical margins benefit from adjuvant RT. Optimal OS is associated with adjuvant RT administered with advanced techniques and cumulative dose more than 65 Gy. LEVEL OF EVIDENCE: 4.
Authors
Dial, BL; Kerr, DL; Lazarides, AL; Catanzano, AA; Green, CL; Risoli, T; Blazer, DG; Goodwin, RC; Brigman, BE; Eward, WC; Larrier, NA; Kirsch, DG; Mendoza-Lattes, SA
MLA Citation
Dial, Brian L., et al. “The Role of Radiotherapy for Chordoma Patients Managed With Surgery: Analysis of the National Cancer Database.Spine (Phila Pa 1976), vol. 45, no. 12, June 2020, pp. E742–51. Pubmed, doi:10.1097/BRS.0000000000003406.
URI
https://scholars.duke.edu/individual/pub1431138
PMID
32032324
Source
pubmed
Published In
Spine (Phila Pa 1976)
Volume
45
Published Date
Start Page
E742
End Page
E751
DOI
10.1097/BRS.0000000000003406