Scott Floyd

Positions:

Gary Hock and Lyn Proctor Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Associate Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Assistant Research Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2002

Yale University School of Medicine

Ph.D. 2002

Yale University

Clinical Investigator, Koch Institute For Integrative Cancer Research

Massachusetts Institute of Technology

Intern, Internal Medicine

Hospital of Saint Raphael

Resident, Harvard Radiation Oncology Program

Harvard Medical School

Grants:

Role of BRD4 in the cancer cell replication stress response

Administered By
Radiation Oncology
Role
Principal Investigator
Start Date
End Date

A 3D ex vivo orthotopic xenograft screening platform to identify radiosensitization targets and druggability in glioma

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Native and bioprinted 3D tissue array platform for predicting cancer metastasis

Administered By
Radiation Oncology
Awarded By
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
End Date

Burroughs Wellcome Fund Agreement

Administered By
Radiation Oncology
Awarded By
Burroughs Wellcome Fund
Role
Principal Investigator
Start Date
End Date

A 3D ex vivo orthotopic xenograft screening platform to identify radiosensitization targets and druggability in glioma

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Evaluation of UVA emission from x-ray megavoltage-irradiated tissues and phantoms.

RECA (Radiotherapy enhanced with Cherenkov photo-activation) is a proposed treatment where the anti-cancer drug psoralen is photo-activated in situ by UVA (Ultraviolet A, 320-400 nm) Cherenkov light (CL) produced directly by the treatment beam itself. In this study, we develop a UVA-imaging technique to quantify relative UVA CL produced by bulk tissues and other phantoms upon clinical x-ray megavoltage irradiation. UVA CL emission (320-400 nm) was quantified in tissue samples of porcine and poultry and in two kinds of solid waters (SW): brown (Virtual Waters, Standard Imaging, WI) and white (Diagnostic Therapy, CIRS, VA), and in 1% agarose gels variously doped with absorbing dye. Quantification was achieved through cumulative imaging of the samples placed in a dark, light-blocking chamber during irradiation on a Varian 21 EX accelerator. UVA imaging required a specialized high-sensitivity cooled camera equipped with UVA lenses and a filter. At 15 MV, white SW emitted [Formula: see text], [Formula: see text] and [Formula: see text] less UVA than chicken breast, pork loin and pork belly, respectively. Similar under-response was observed at 6 MV. Brown SW had [Formula: see text] less UVA emission than white SW at 15 MV, and negligible emission at 6 MV. Agarose samples (1% by weight) doped with 250 ppm India ink exhibited equivalent UVA CL emission to chicken breast (within 8%). The results confirm that for the same absorbed dose, SW emits less UVA light than the tissue samples, indicating that prior in vitro studies utilizing SW as the CL-generating source may have underestimated the RECA therapeutic effect. Agarose doped with 250 ppm India ink is a convenient tissue-equivalent phantom for further work.
Authors
Jain, S; Yoon, SW; Zhang, X; Adamson, J; Floyd, S; Oldham, M
MLA Citation
Jain, Sagarika, et al. “Evaluation of UVA emission from x-ray megavoltage-irradiated tissues and phantoms.Phys Med Biol, vol. 64, no. 22, Nov. 2019, p. 225017. Pubmed, doi:10.1088/1361-6560/ab4333.
URI
https://scholars.duke.edu/individual/pub1409900
PMID
31505474
Source
pubmed
Published In
Phys Med Biol
Volume
64
Published Date
Start Page
225017
DOI
10.1088/1361-6560/ab4333

Radiation Therapy Practice Patterns for Brain Metastases in the United States in the Stereotactic Radiosurgery Era.

Purpose:Utilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has increased, prompting reassessment of whole brain radiation therapy (WBRT). A pattern of care analysis of SRS and WBRT dose-fractionations was performed in patients presenting with BM at the time of cancer diagnosis. Methods and Materials:Adults with BM at cancer diagnosis between 2010 to 2015 and no prior malignancy were identified in the National Cancer Database. SRS was defined using published thresholds. Short (ShWBRT), standard (StWBRT), and extended (ExWBRT) dose-fractionations were defined as 4 to 9, 10 to 15, and >15 fractions. Radioresistant histology was defined as melanoma, renal cell carcinoma, sarcoma or spindle cell, or gastrointestinal primary. Results:Of 4,087,967 adults with their first lifetime cancer, 90,388 (2.2%) had BM at initial diagnosis. Of these, 11,486 (12.7%) received SRS and 24,262 (26.8%) WBRT as first-course radiation therapy. The proportion of annual WBRT use decreased from 27.8% to 23.5% of newly diagnosed patients, and SRS increased from 8.7% to 17.9%. Common dose-fractionations were 30 Gy in 10 fractions (56.8%) for WBRT and 20 Gy in 1 fraction (13.0%) for SRS. On multivariate analysis, factors significantly associated with SRS versus WBRT included later year of diagnosis (2015 vs 2010, adjusted odds ratio [aOR] = 2.4), radioresistance (aOR = 2.0), academic facility (aOR = 1.9), highest income quartile (aOR = 1.6), chemotherapy administration (aOR = 1.4), and longer travel distance (>15 vs < 5 miles, aOR = 1.4). Linear regression revealed significant ExWBRT reductions (-22.4%/y, R2 = 0.97, P < .001) and no significant change for ShWBRT or StWBRT. Patients were significantly more likely to receive ShWBRT than StWBRT if not treated with chemotherapy (aOR = 3.5). Conclusions:Utilization of WBRT, particularly ExWBRT, decreased while SRS utilization doubled as the first radiation therapy course in patients with BM at diagnosis. Patients with radioresistant histologies were more likely to receive SRS. Those not receiving chemotherapy, potentially owing to poor performance status, were less likely to receive SRS and more likely to receive ShWBRT.
Authors
Barbour, AB; Jacobs, CD; Williamson, H; Floyd, SR; Suneja, G; Torok, JA; Kirkpatrick, JP
MLA Citation
Barbour, Andrew B., et al. “Radiation Therapy Practice Patterns for Brain Metastases in the United States in the Stereotactic Radiosurgery Era.Advances in Radiation Oncology, vol. 5, no. 1, Jan. 2020, pp. 43–52. Epmc, doi:10.1016/j.adro.2019.07.012.
URI
https://scholars.duke.edu/individual/pub1410090
PMID
32051889
Source
epmc
Published In
Advances in Radiation Oncology
Volume
5
Published Date
Start Page
43
End Page
52
DOI
10.1016/j.adro.2019.07.012

B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.

BACKGROUND: The dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM. METHODS: We compared mRNA expression of antigens in GBM using TCGA data, and validated B7-H3 expression by immunohistochemistry. We then tested the antitumor activity of B7-H3-redirected CAR-T cells against GBM cell lines and patient-derived GBM neurospheres in vitro and in xenograft murine models. FINDINGS: B7-H3 mRNA and protein are overexpressed in GBM relative to normal brain in all GBM subtypes. Of the 46 specimens analyzed by immunohistochemistry, 76% showed high B7-H3 expression, 22% had detectable, but low B7-H3 expression and 2% were negative, as was normal brain. All 20 patient-derived neurospheres showed ubiquitous B7-H3 expression. B7-H3-redirected CAR-T cells effectively targeted GBM cell lines and neurospheres in vitro and in vivo. No significant differences were found between CD28 and 4-1BB co-stimulation, although CD28-co-stimulated CAR-T cells released more inflammatory cytokines. INTERPRETATION: We demonstrated that B7-H3 is highly expressed in GBM specimens and neurospheres that contain putative cancer stem cells, and that B7-H3-redirected CAR-T cells can effectively control tumor growth. Therefore, B7-H3 represents a promising target in GBM. FUND: Alex's Lemonade Stand Foundation; Il Fondo di Gio Onlus; National Cancer Institute; Burroughs Wellcome Fund.
Authors
Nehama, D; Di Ianni, N; Musio, S; Du, H; Patané, M; Pollo, B; Finocchiaro, G; Park, JJH; Dunn, DE; Edwards, DS; Damrauer, JS; Hudson, H; Floyd, SR; Ferrone, S; Savoldo, B; Pellegatta, S; Dotti, G
MLA Citation
Nehama, Dean, et al. “B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.Ebiomedicine, vol. 47, Sept. 2019, pp. 33–43. Pubmed, doi:10.1016/j.ebiom.2019.08.030.
URI
https://scholars.duke.edu/individual/pub1406594
PMID
31466914
Source
pubmed
Published In
Ebiomedicine
Volume
47
Published Date
Start Page
33
End Page
43
DOI
10.1016/j.ebiom.2019.08.030

The effect of MLC leaf width in single-isocenter multi-target radiosurgery with volumetric modulated arc therapy.

Purpose: Single-isocenter multi-target (SIMT) volumetric modulated arc therapy (VMAT) is primarily limited to linear accelerators utilizing 2.5 mm leaf width MLCs. We explore feasibility of applying this technique to linear accelerators utilizing MLCs with leaf width of 5 mm. Methods: Twenty patients with 3-10 intracranial brain metastases originally treated with 2.5 mm MLCs were re-planned using 5 mm MLCs and relevant dosimetric indices were compared. We also evaluated various strategies of adding VMAT arcs to mitigate degradations of dose quality values. Results: Wider MLCs caused small changes in total MUs (5827 ± 2334 vs 5572 ± 2220, p = 0.006), and conformity index (CI) (2.22% ± 0.05%, p = 0.045), but produced more substantial increases in brain V30%[%] and V50%[%] (27.75% ± 0.16% and 20.04% ± 0.13% respectively, p < 0.001 for both), and V12Gy[cc] (16.91% ± 0.12%, p < 0.001). Conclusion: SIMT radiosurgery delivered via VMAT using 5 mm wide MLCs can achieve similar CI compared to that using 2.5 mm leaf width MLCs but with moderately increased isodose spill, which can be only partially mitigated by increasing the number of VMAT arcs.
Authors
Abisheva, Z; Floyd, SR; Salama, JK; Kirkpatrick, J; Yin, F-F; Moravan, MJ; Giles, W; Adamson, J
MLA Citation
Abisheva, Zhanerke, et al. “The effect of MLC leaf width in single-isocenter multi-target radiosurgery with volumetric modulated arc therapy.J Radiosurg Sbrt, vol. 6, no. 2, 2019, pp. 131–38.
URI
https://scholars.duke.edu/individual/pub1410134
PMID
31641549
Source
pubmed
Published In
J Radiosurg Sbrt
Volume
6
Published Date
Start Page
131
End Page
138

A Multivariate Computational Method to Analyze High-Content RNAi Screening Data.

High-content screening (HCS) using RNA interference (RNAi) in combination with automated microscopy is a powerful investigative tool to explore complex biological processes. However, despite the plethora of data generated from these screens, little progress has been made in analyzing HC data using multivariate methods that exploit the full richness of multidimensional data. We developed a novel multivariate method for HCS, multivariate robust analysis method (M-RAM), integrating image feature selection with ranking of perturbations for hit identification, and applied this method to an HC RNAi screen to discover novel components of the DNA damage response in an osteosarcoma cell line. M-RAM automatically selects the most informative phenotypic readouts and time points to facilitate the more efficient design of follow-up experiments and enhance biological understanding. Our method outperforms univariate hit identification and identifies relevant genes that these approaches would have missed. We found that statistical cell-to-cell variation in phenotypic responses is an important predictor of hits in RNAi-directed image-based screens. Genes that we identified as modulators of DNA damage signaling in U2OS cells include B-Raf, a cancer driver gene in multiple tumor types, whose role in DNA damage signaling we confirm experimentally, and multiple subunits of protein kinase A.
Authors
Rameseder, J; Krismer, K; Dayma, Y; Ehrenberger, T; Hwang, MK; Airoldi, EM; Floyd, SR; Yaffe, MB
MLA Citation
Rameseder, Jonathan, et al. “A Multivariate Computational Method to Analyze High-Content RNAi Screening Data.J Biomol Screen, vol. 20, no. 8, Sept. 2015, pp. 985–97. Pubmed, doi:10.1177/1087057115583037.
URI
https://scholars.duke.edu/individual/pub1131512
PMID
25918037
Source
pubmed
Published In
J Biomol Screen
Volume
20
Published Date
Start Page
985
End Page
997
DOI
10.1177/1087057115583037