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 at Chapel Hill

Intern, Surgery

University of Nebraska at Lincoln

Resident, Orthopaedic Surgery

University of Nebraska at Lincoln

Fellow, Orthopaedic Oncology

Boston University

Grants:

Fresh Tissue Lab Agreement

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

Protocol Number: 14-03-PATHOLHUM-02

Administered By
Orthopaedics
Role
Principal Investigator
Start Date
End Date

Publications:

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

Epidemiologic and survival trends in adult primary bone tumors of the spine.

BACKGROUND CONTEXT: Malignant primary spinal tumors are rare making it difficult to perform large studies comparing epidemiologic, survival, and treatment trends. We investigated the largest registry of primary bone tumors, the National Cancer Database (NCDB), to compare epidemiologic and survival trends among these tumors. PURPOSE: To use the NCDB to describe current epidemiologic trends, treatment modalities, and overall survival rates in patients with chordomas, osteosarcomas, chondrosarcomas, and Ewing sarcomas of the mobile spine. The secondary objective was to determine prognostic factors that impact overall survival rates. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 1,011 patients with primary bone tumors of the spine (377 chordomas, 223 chondrosarcomas, 278 Ewing sarcomas, and 133 osteosarcomas). OUTCOME MEASURES: Five-year survival. METHODS: We reviewed the records of 1,011 patients in the NCDB from 2004 through 2015 with histologically confirmed primary osteosarcoma, chondrosarcoma, Ewing sarcoma, or chordoma of the spine. Demographic, clinical, and outcomes data were compiled and compared using chi-squared tests and ANOVA. Long-term survival was compared using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multivariate analysis was performed to determine survival determinants. RESULTS: Surgical resection was the primary mode of treatment for chondrosarcoma (90%), chordoma (84%), and osteosarcoma (80%). The treatment for Ewing sarcoma was multimodal involving chemotherapy, radiation therapy, and surgical resection. Five-year survival rates varied significantly with chordomas and chondrosarcomas having the greatest survival (70% and 69%), osteosarcomas having the worse survival (38%), and Ewing having intermediate 5-year survival at 62% (overall log-rank p<.0001). Multivariate analysis demonstrated significantly improved 5-year survival rates with younger age at diagnosis, private insurance status, lower comorbidity score, lower tumor grade, smaller tumor size, surgical resection, and negative surgical margin. Radiation therapy only improved survival for Ewing sarcoma. CONCLUSIONS: This study provides the most comprehensive description of the epidemiologic, treatment, and survival trends of primary bone tumors of the mobile spine. Second, patient and tumor characteristics associated with improved 5-year survival were identified using a multivariate model.
Authors
Kerr, DL; Dial, BL; Lazarides, AL; Catanzano, AA; Lane, WO; Blazer, DG; Brigman, BE; Mendoza-Lattes, S; Eward, WC; Erickson, ME
MLA Citation
Kerr, David L., et al. “Epidemiologic and survival trends in adult primary bone tumors of the spine..” Spine J, vol. 19, no. 12, Dec. 2019, pp. 1941–49. Pubmed, doi:10.1016/j.spinee.2019.07.003.
URI
https://scholars.duke.edu/individual/pub1398171
PMID
31306757
Source
pubmed
Published In
Spine J
Volume
19
Published Date
Start Page
1941
End Page
1949
DOI
10.1016/j.spinee.2019.07.003

New Techniques for Diagnosis and Treatment of Musculoskeletal Tumors: Methods of Intraoperative Margin Detection

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Although frozen section analysis remains the standard for intraoperative margin detection for some cancers, there are critical limitations with using this method in the treatment of musculoskeletal tumors. Extensive work has been done to develop more accurate methods of intraoperative assessment of resection margins. Successful limb-salvage surgery requires adequate resection of tumor without excessive resection of normal tissue. Traditional imaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography scans have been adapted for use with computer navigation to provide more accurate intraoperative assessment and resection. However, these modalities are not without their own disadvantages, such as cost and availability. Newer technologies are being investigated to evaluate tumors intraoperatively at the microscopic and molecular level using spectroscopy and fluorescence imaging. Despite the promise of these intraoperative modalities, there are limited long-Term outcome studies to validate their efficacy. In this symposium, we discuss the current advances in modalities for intraoperative margin assessment and their application in treating musculoskeletal tumors. In addition, we outline the existing evidence, albeit limited, of their short, and long-Term successes.
Authors
Catanzano, AA; Ryan, SP; Lazarides, AL; Brigman, BE; Eward, WC
MLA Citation
Catanzano, A. A., et al. “New Techniques for Diagnosis and Treatment of Musculoskeletal Tumors: Methods of Intraoperative Margin Detection.” Techniques in Orthopaedics, vol. 33, no. 3, 2018, pp. 148–57. Scopus, doi:10.1097/BTO.0000000000000290.
URI
https://scholars.duke.edu/individual/pub1350801
Source
scopus
Published In
Techniques in Orthopaedics (Rockville, Md.)
Volume
33
Published Date
Start Page
148
End Page
157
DOI
10.1097/BTO.0000000000000290

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.
Authors
Whitley, MJ; Cardona, DM; Lazarides, AL; Spasojevic, I; Ferrer, JM; Cahill, J; Lee, C-L; Snuderl, M; Blazer, DG; Hwang, ES; Greenup, RA; Mosca, PJ; Mito, JK; Cuneo, KC; Larrier, NA; O'Reilly, EK; Riedel, RF; Eward, WC; Strasfeld, DB; Fukumura, D; Jain, RK; Lee, WD; Griffith, LG; Bawendi, MG; Kirsch, DG; Brigman, BE
MLA Citation
Whitley, Melodi Javid, et al. “A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer..” Sci Transl Med, vol. 8, no. 320, Jan. 2016. Pubmed, doi:10.1126/scitranslmed.aad0293.
URI
https://scholars.duke.edu/individual/pub1112634
PMID
26738797
Source
pubmed
Published In
Sci Transl Med
Volume
8
Published Date
Start Page
320ra4
DOI
10.1126/scitranslmed.aad0293

Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents.

PURPOSE: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. METHODS AND MATERIALS: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activated fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. RESULTS: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. CONCLUSIONS: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.
Authors
Cuneo, KC; Mito, JK; Javid, MP; Ferrer, JM; Kim, Y; Lee, WD; Bawendi, MG; Brigman, BE; Kirsch, DG
MLA Citation
Cuneo, Kyle C., et al. “Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents..” Int J Radiat Oncol Biol Phys, vol. 86, no. 1, May 2013, pp. 136–42. Pubmed, doi:10.1016/j.ijrobp.2012.12.007.
URI
https://scholars.duke.edu/individual/pub932656
PMID
23391816
Source
pubmed
Published In
Int J Radiat Oncol Biol Phys
Volume
86
Published Date
Start Page
136
End Page
142
DOI
10.1016/j.ijrobp.2012.12.007