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Floyd, Scott Richard

Positions:

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

M.D. — Yale University School of Medicine

Ph.D. 2002

Ph.D. — 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:

Burroughs Wellcome Fund Agreement

Administered By
Radiation Oncology
AwardedBy
Burroughs Wellcome Fund
Role
Principal Investigator
Start Date
September 01, 2015
End Date
August 31, 2018

Publications:

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, J, Krismer, K, Dayma, Y, Ehrenberger, T, Hwang, MK, Airoldi, EM, Floyd, SR, and Yaffe, MB. "A Multivariate Computational Method to Analyze High-Content RNAi Screening Data." Journal of biomolecular screening 20.8 (September 2015): 985-997.
PMID
25918037
Source
epmc
Published In
Journal of Biomolecular Screening
Volume
20
Issue
8
Publish Date
2015
Start Page
985
End Page
997
DOI
10.1177/1087057115583037

Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers.

Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC.The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients.We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44-1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years.BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC.

Authors
Rangachari, D; Yamaguchi, N; VanderLaan, PA; Folch, E; Mahadevan, A; Floyd, SR; Uhlmann, EJ; Wong, ET; Dahlberg, SE; Huberman, MS; Costa, DB
MLA Citation
Rangachari, D, Yamaguchi, N, VanderLaan, PA, Folch, E, Mahadevan, A, Floyd, SR, Uhlmann, EJ, Wong, ET, Dahlberg, SE, Huberman, MS, and Costa, DB. "Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers." Lung cancer (Amsterdam, Netherlands) 88.1 (April 2015): 108-111.
PMID
25682925
Source
epmc
Published In
Lung Cancer
Volume
88
Issue
1
Publish Date
2015
Start Page
108
End Page
111
DOI
10.1016/j.lungcan.2015.01.020

Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review.

Ipilimumab improves survival in metastatic melanoma patients. This population frequently develops brain metastases, which have been associated with poor survival and are often treated with radiation. Therefore, outcomes following ipilimumab and radiation are of interest, especially given case reports and animal studies suggest combined treatment may generate abscopal responses outside the radiation field.We reviewed sixteen consecutive melanoma patients who received 1 to 8 courses of radiation, with a sum total of 51, systematically evaluating abscopal responses by following the largest extra-cranial lesion. We also reviewed other series of patients treated with cranial radiation and ipilimumab. Our patients received between 1 and 8 courses of cranial radiation. Four patients received radiation concurrently with ipilimumab. Median survival was 14 months, and 17 months in patients initially treated with SRS. Interestingly, after radiotherapy, there was a 2.8-fold increased likelihood that the rate of extra-cranial index lesion response improved that didn't reach statistical significance (p = 0.07); this was more pronounced when ipilimumab was administered within three months of radiation (p < 0.01).Our experience and review of recently published series suggest ipilimumab and cranial radiation is well tolerated and can result in prolonged survival. Timing of ipilimumab administration in relation to radiation may impact outcomes. Additionally, our results demonstrate a trend for favorable systemic response following radiotherapy worthy of further evaluation in studies powered to detect potential synergies between radiation and immunotherapy.

Authors
Schoenfeld, JD; Mahadevan, A; Floyd, SR; Dyer, MA; Catalano, PJ; Alexander, BM; McDermott, DF; Kaplan, ID
MLA Citation
Schoenfeld, JD, Mahadevan, A, Floyd, SR, Dyer, MA, Catalano, PJ, Alexander, BM, McDermott, DF, and Kaplan, ID. "Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review." Journal for immunotherapy of cancer 3 (January 2015): 50-.
PMID
26672895
Source
epmc
Published In
Journal for ImmunoTherapy of Cancer
Volume
3
Publish Date
2015
Start Page
50
DOI
10.1186/s40425-015-0095-8

Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy.

Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia.Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means.All six patients had fully preserved scalp hair and remained clinically cognitively intact 1-3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area.HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.

Authors
Mahadevan, A; Sampson, C; LaRosa, S; Floyd, SR; Wong, ET; Uhlmann, EJ; Sengupta, S; Kasper, EM
MLA Citation
Mahadevan, A, Sampson, C, LaRosa, S, Floyd, SR, Wong, ET, Uhlmann, EJ, Sengupta, S, and Kasper, EM. "Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy." Radiation oncology (London, England) 10 (January 2015): 245-.
PMID
26611656
Source
epmc
Published In
Radiation Oncology
Volume
10
Publish Date
2015
Start Page
245
DOI
10.1186/s13014-015-0555-9

Stereotactic radiosurgery for brain metastases from malignant melanoma

Authors
Kasper, E; Lam, F; Mahadevan, A; Wong, E; Chen, C; Christ, S; Floyd, S
MLA Citation
Kasper, E, Lam, F, Mahadevan, A, Wong, E, Chen, C, Christ, S, and Floyd, S. "Stereotactic radiosurgery for brain metastases from malignant melanoma." Surgical Neurology International 6.13 (2015): 355-355.
Source
crossref
Published In
Surgical Neurology International
Volume
6
Issue
13
Publish Date
2015
Start Page
355
End Page
355
DOI
10.4103/2152-7806.163315

The role of whole brain radiation therapy in the management of melanoma brain metastases.

BACKGROUND: Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as "radioresistant," the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). METHODS: We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). CONCLUSIONS: Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials.

Authors
Dyer, MA; Arvold, ND; Chen, YH; Pinnell, NE; Mitin, T; Lee, EQ; Hodi, FS; Ibrahim, N; Weiss, SE; Kelly, PJ; Floyd, SR; Mahadevan, A; Alexander, BM
MLA Citation
Dyer, MA, Arvold, ND, Chen, YH, Pinnell, NE, Mitin, T, Lee, EQ, Hodi, FS, Ibrahim, N, Weiss, SE, Kelly, PJ, Floyd, SR, Mahadevan, A, and Alexander, BM. "The role of whole brain radiation therapy in the management of melanoma brain metastases." Radiation oncology (London, England) 9 (January 2014): 143-.
PMID
24954062
Source
epmc
Published In
Radiation Oncology
Volume
9
Publish Date
2014
Start Page
143
DOI
10.1186/1748-717x-9-143

The bromodomain protein Brd4 insulates chromatin from DNA damage signalling.

DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death. Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response. Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage.

Authors
Floyd, SR; Pacold, ME; Huang, Q; Clarke, SM; Lam, FC; Cannell, IG; Bryson, BD; Rameseder, J; Lee, MJ; Blake, EJ; Fydrych, A; Ho, R; Greenberger, BA; Chen, GC; Maffa, A; Del Rosario, AM; Root, DE; Carpenter, AE; Hahn, WC; Sabatini, DM; Chen, CC; White, FM; Bradner, JE; Yaffe, MB
MLA Citation
Floyd, SR, Pacold, ME, Huang, Q, Clarke, SM, Lam, FC, Cannell, IG, Bryson, BD, Rameseder, J, Lee, MJ, Blake, EJ, Fydrych, A, Ho, R, Greenberger, BA, Chen, GC, Maffa, A, Del Rosario, AM, Root, DE, Carpenter, AE, Hahn, WC, Sabatini, DM, Chen, CC, White, FM, Bradner, JE, and Yaffe, MB. "The bromodomain protein Brd4 insulates chromatin from DNA damage signalling." Nature 498.7453 (June 2, 2013): 246-250.
PMID
23728299
Source
epmc
Published In
Nature
Volume
498
Issue
7453
Publish Date
2013
Start Page
246
End Page
250
DOI
10.1038/nature12147

Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.

A key modality of non-surgical cancer management is DNA damaging therapy that causes DNA double-strand breaks that are preferentially toxic to rapidly dividing cancer cells. Double-strand break repair capacity is recognized as an important mechanism in drug resistance and is therefore a potential target for adjuvant chemotherapy. Additionally, spontaneous and environmentally induced DSBs are known to promote cancer, making DSB evaluation important as a tool in epidemiology, clinical evaluation and in the development of novel pharmaceuticals. Currently available assays to detect double-strand breaks are limited in throughput and specificity and offer minimal information concerning the kinetics of repair. Here, we present the CometChip, a 96-well platform that enables assessment of double-strand break levels and repair capacity of multiple cell types and conditions in parallel and integrates with standard high-throughput screening and analysis technologies. We demonstrate the ability to detect multiple genetic deficiencies in double-strand break repair and evaluate a set of clinically relevant chemical inhibitors of one of the major double-strand break repair pathways, non-homologous end-joining. While other high-throughput repair assays measure residual damage or indirect markers of damage, the CometChip detects physical double-strand breaks, providing direct measurement of damage induction and repair capacity, which may be useful in developing and implementing treatment strategies with reduced side effects.

Authors
Weingeist, DM; Ge, J; Wood, DK; Mutamba, JT; Huang, Q; Rowland, EA; Yaffe, MB; Floyd, S; Engelward, BP
MLA Citation
Weingeist, DM, Ge, J, Wood, DK, Mutamba, JT, Huang, Q, Rowland, EA, Yaffe, MB, Floyd, S, and Engelward, BP. "Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors." Cell cycle (Georgetown, Tex.) 12.6 (March 2013): 907-915.
PMID
23422001
Source
epmc
Published In
Cell Cycle
Volume
12
Issue
6
Publish Date
2013
Start Page
907
End Page
915
DOI
10.4161/cc.23880

Melanoma brain metastasis: overview of current management and emerging targeted therapies.

The high rate of brain metastasis in patients with advanced melanoma has been a clinical challenge for oncologists. Despite considerable progress made in the management of advanced melanoma over the past two decades, improvement in overall survival has been elusive. This is due to the high incidence of CNS metastases, which progress relentlessly and which are only anecdotally responsive to systemic therapies. Surgery, stereotactic radiosurgery and whole-brain radiotherapy with or without cytotoxic chemotherapy remain the mainstay of treatment. However, new drugs have been developed based on our improved understanding of the molecular signaling mechanisms responsible for host immune tolerance and for melanoma growth. In 2011, the US FDA approved two agents, one antagonizing each of these processes, for the treatment of advanced melanoma. The first is ipilimumab, an anti-CTLA-4 monoclonal antibody that enhances cellular immunity and reduces tolerance to tumor-associated antigens. The second is vemurafenib, an inhibitor that blocks the abnormal signaling for melanoma cellular growth in tumors that carry the BRAF(V600E) mutation. Both drugs have anecdotal clinical activity for brain metastasis and are being evaluated in clinical trial settings. Additional clinical trials of newer agents involving these pathways are also showing promise. Therefore, targeted therapies must be incorporated into the multimodality management of melanoma brain metastasis.

Authors
Fonkem, E; Uhlmann, EJ; Floyd, SR; Mahadevan, A; Kasper, E; Eton, O; Wong, ET
MLA Citation
Fonkem, E, Uhlmann, EJ, Floyd, SR, Mahadevan, A, Kasper, E, Eton, O, and Wong, ET. "Melanoma brain metastasis: overview of current management and emerging targeted therapies." Expert review of neurotherapeutics 12.10 (October 2012): 1207-1215. (Review)
PMID
23082737
Source
epmc
Published In
Expert Review of Neurotherapeutics
Volume
12
Issue
10
Publish Date
2012
Start Page
1207
End Page
1215
DOI
10.1586/ern.12.111

Frameless angiogram-based stereotactic radiosurgery for treatment of arteriovenous malformations.

PURPOSE: Stereotactic radiosurgery (SRS) is an effective alternative to microsurgical resection or embolization for definitive treatment of arteriovenous malformations (AVMs). Digital subtraction angiography (DSA) is the gold standard for pretreatment diagnosis and characterization of vascular anatomy, but requires rigid frame (skull) immobilization when used in combination with SRS. With the advent of advanced proton and image-guided photon delivery systems, SRS treatment is increasingly migrating to frameless platforms, which are incompatible with frame-based DSA. Without DSA as the primary image, target definition may be less than optimal, in some cases precluding the ability to treat with a frameless system. This article reports a novel solution. METHODS AND MATERIALS: Fiducial markers are implanted into the patient's skull before angiography. Angiography is performed according to the standard clinical protocol, but, in contrast to the previous practice, without the rigid frame. Separate images of a specially designed localizer box are subsequently obtained. A target volume projected on DSA can be transferred to the localizer system in three dimensions, and in turn be transferred to multiple CT slices using the implanted fiducials. Combined with other imaging modalities, this "virtual frame" approach yields a highly precise treatment plan that can be delivered by frameless SRS technologies. RESULTS: Phantom measurements for point and volume targets have been performed. The overall uncertainty of placing a point target to CT is 0.4 mm. For volume targets, deviation of the transformed contour from the target CT image is within 0.6 mm. The algorithm and software are robust. The method has been applied clinically, with reliable results. CONCLUSIONS: A novel and reproducible method for frameless SRS of AVMs has been developed that enables the use of DSA without the requirement for rigid immobilization. Multiple pairs of DSA can be used for better conformality. Further improvement, including using nonimplanted fiducials, is potentially feasible.

Authors
Lu, XQ; Mahadevan, A; Mathiowitz, G; Lin, PJ; Thomas, A; Kasper, EM; Floyd, SR; Holupka, E; La Rosa, S; Wang, F; Stevenson, MA
MLA Citation
Lu, XQ, Mahadevan, A, Mathiowitz, G, Lin, PJ, Thomas, A, Kasper, EM, Floyd, SR, Holupka, E, La Rosa, S, Wang, F, and Stevenson, MA. "Frameless angiogram-based stereotactic radiosurgery for treatment of arteriovenous malformations." International journal of radiation oncology, biology, physics 84.1 (September 2012): 274-282.
PMID
22284685
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
84
Issue
1
Publish Date
2012
Start Page
274
End Page
282
DOI
10.1016/j.ijrobp.2011.10.044

Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy: Goulart J, Truong P, Woods R, et al (Univ of British Columbia, Vancouver, Canada; British Columbia Cancer Agency, Vancouver, Canada) Int J Radiat Oncol Biol Phys 80:758-764, 2011

Authors
Floyd, SR
MLA Citation
Floyd, SR. "Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy: Goulart J, Truong P, Woods R, et al (Univ of British Columbia, Vancouver, Canada; British Columbia Cancer Agency, Vancouver, Canada) Int J Radiat Oncol Biol Phys 80:758-764, 2011." Breast Diseases 23.2 (May 24, 2012): 185-187.
Source
scopus
Published In
Breast Diseases: A Year Book Quarterly
Volume
23
Issue
2
Publish Date
2012
Start Page
185
End Page
187
DOI
10.1016/j.breastdis.2012.03.028

Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy × 3 daily fractions regimen.

Development of hypofractionated stereotactic radiosurgery (HSRS) has expanded the size of lesion that can be safely treated by focused radiation in a limited number of treatment sessions. However, clinical data regarding the efficacy and morbidity of HSRS in the treatment of cerebral metastasis is lacking. Here, we review our experience with CyberKnife(®) HSRS for this indication. From 2005 to 2010, we identified 37 patients with large (>3 cm in diameter) cerebral metastases resection cavity that was treated with HSRS. This constituted approximately 8% of all treated resection cavities. We reviewed dose regimens, local control, distal control, and treatment associated morbidities. Primary sites for the metastatic lesions included: lung (n = 10), melanoma (n = 12), breast (n = 9), kidney (n = 4), and colon (n = 2). All patients underwent resection of the cerebral metastasis and received 800 cGy × 3 daily fractions to the resection cavity. Of the 37 patients treated, one-year follow-up data was available for 35 patients. The median survival was 5.5 months. Actuarial local control rate at 6 months was 80%. Local failures did not correlate with prior WBRT, or tumor histology. Distant recurrence occurred in 7 of the 35 patients. Morbidities associated with HSRS totaled 9%, including radiation necrosis (n = 1, 2.9%), prolonged steroid use (n = 1, 2.9%), and new-onset seizures (n = 1, 2.9%). This study demonstrates the safety and efficacy of an 800 cGy × 3 daily fractions CyberKnife(®) HSRS regimen for irradiation of large resection cavity. The efficacy compares favorably to historical data derived from patients undergoing WBRT, SRS, or brachytherapy.

Authors
Wang, CC; Floyd, SR; Chang, CH; Warnke, PC; Chio, CC; Kasper, EM; Mahadevan, A; Wong, ET; Chen, CC
MLA Citation
Wang, CC, Floyd, SR, Chang, CH, Warnke, PC, Chio, CC, Kasper, EM, Mahadevan, A, Wong, ET, and Chen, CC. "Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy × 3 daily fractions regimen." Journal of neuro-oncology 106.3 (February 2012): 601-610.
PMID
21879395
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
106
Issue
3
Publish Date
2012
Start Page
601
End Page
610
DOI
10.1007/s11060-011-0697-z

Stereotactic body radiotherapy reirradiation for recurrent epidural spinal metastases.

PURPOSE: When patients show progression after conventional fractionated radiation for spine metastasis, further radiation and surgery may not be options. Stereotactic body radiotherapy (SBRT) has been successfully used in treatment of the spine and may be applicable in these cases. We report the use of SBRT for 60 consecutive patients (81 lesions) who had radiological progressive spine metastasis with epidural involvement after previous radiation for spine metastasis. METHODS AND MATERIALS: SBRT was used with fiducial and vertebral anatomy-based targeting. The radiation dose was prescribed based on the extent of spinal canal involvement; the dose was 8 Gy×3=24 Gy when the tumor did not touch the spinal cord and 5 to 6 Gyx5=25 to 30 Gy when the tumor abutted the cord. The cord surface received up to the prescription dose with no hot spots in the cord. RESULTS: The median overall survival was 11 months, and the median progression-free survival was 9 months. Overall, 93% of patients had stable or improved disease while 7% of patients showed disease progression; 65% of patients had pain relief. There was no significant toxicity other than fatigue. CONCLUSIONS: SBRT is feasible and appears to be an effective treatment modality for reirradiation after conventional palliative radiation fails for spine metastasis patients.

Authors
Mahadevan, A; Floyd, S; Wong, E; Jeyapalan, S; Groff, M; Kasper, E
MLA Citation
Mahadevan, A, Floyd, S, Wong, E, Jeyapalan, S, Groff, M, and Kasper, E. "Stereotactic body radiotherapy reirradiation for recurrent epidural spinal metastases." International journal of radiation oncology, biology, physics 81.5 (December 2011): 1500-1505.
PMID
20950944
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
81
Issue
5
Publish Date
2011
Start Page
1500
End Page
1505
DOI
10.1016/j.ijrobp.2010.08.012

Clinical outcome after hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors.

OBJECTIVE: Surgical resection of skull base tumors can be associated with significant morbidity. In cases where the risks outweigh the benefits, radiation therapy can offer an alternative means to effectively control tumor growth. However, the optimal dose regime for radiation therapy remains controversial. The objective of this study was to assess the neurological outcome, local control rate and morbidity associated with a 5-fraction regime of hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors. METHODS: Twenty-six patients presenting with two of the most prevalent benign skull base tumors were included in the study. The tumors comprised 16 meningiomas and 10 acoustic neuromas. All patients exhibited preserved cranial nerve function prior to treatment, and a detailed audiological assessment was performed pre- and post-treatment for those patients with acoustic neuroma. Stereotactic radiosurgery was administered with the frameless CyberKnife Robotic Radiosurgery System. In each case, a 5-fraction HSRT regime was used: a dose of 5 Gy × 5 = 25 Gy to 6 Gy × 5 = 30 Gy was prescribed for skull base meningiomas, and 5 Gy × 5 = 25 Gy was prescribed for acoustic neuromas. RESULTS: The clinical and radiographic median follow-up was 22 months (range: 6-54 months). Radiological assessment showed local control in all 26 tumors (100%), and in 5/26 patients (20%) the tumor showed a decrease in size. Cranial nerve function was preserved in all cases thus far studied; however, 28% of patients had transient Grade II side effects, including fatigue, headaches, unsteadiness and transient subjective worsening of hearing. In two of these patients, the period of transient worsening of hearing was associated with a temporary increase in the size of the tumor on control T2 MR images, consistent with radiation-induced edema. One patient had transient decrease in visual acuity from treatment-related edema. At the last follow-up, 3/16 patients with meningiomas (19%) and 2/10 with acoustic neuromas (20%) showed a decrease in tumor volume and improvement in hearing. CONCLUSION: A 5-fraction stereotactic radiotherapy regime, as used in this study, seems to be effective for local control of benign skull base tumors in this early follow-up evaluation. Neurological function preservation is excellent with this short regime in the early post-treatment period, but long-term follow-up is crucial for validation.

Authors
Mahadevan, A; Floyd, S; Wong, E; Chen, C; Kasper, E
MLA Citation
Mahadevan, A, Floyd, S, Wong, E, Chen, C, and Kasper, E. "Clinical outcome after hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors." Computer aided surgery : official journal of the International Society for Computer Aided Surgery 16.3 (January 2011): 112-120.
PMID
21466421
Source
epmc
Published In
Computer Aided Surgery (Wiley)
Volume
16
Issue
3
Publish Date
2011
Start Page
112
End Page
120
DOI
10.3109/10929088.2011.565160

Post-mastectomy radiation in large node-negative breast tumors: does size really matter?

Treatment decisions regarding local control can be particularly challenging for T3N0 breast tumors because of difficulty in estimating rates of local failure after mastectomy. Reports in the literature detailing the rates of local failure vary widely, likely owing to the uncommon incidence of this clinical situation. The literature regarding this clinical scenario is reviewed, including recent reports that specifically address the issue of local failure rates after mastectomy in the absence of radiation for large node-negative breast tumors.

Authors
Floyd, SR; Taghian, AG
MLA Citation
Floyd, SR, and Taghian, AG. "Post-mastectomy radiation in large node-negative breast tumors: does size really matter?." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 91.1 (April 2009): 33-37. (Review)
PMID
19201501
Source
epmc
Published In
Radiotherapy & Oncology
Volume
91
Issue
1
Publish Date
2009
Start Page
33
End Page
37
DOI
10.1016/j.radonc.2008.09.015

The role of postmastectomy radiation in node-negative breast tumors larger than 5 cm

Authors
Martin, NE; Floyd, S; Raad, RA; Taghian, A
MLA Citation
Martin, NE, Floyd, S, Raad, RA, and Taghian, A. "The role of postmastectomy radiation in node-negative breast tumors larger than 5 cm." American Journal of Hematology/ Oncology 6.4 (April 1, 2007): 197-199.
Source
scopus
Published In
American Journal of Oncology Review
Volume
6
Issue
4
Publish Date
2007
Start Page
197
End Page
199

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger.

PURPOSE: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. METHODS AND MATERIALS: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. RESULTS: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p=0.017) and in Cox proportional hazards analysis (p=0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. CONCLUSIONS: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy.

Authors
Floyd, SR; Buchholz, TA; Haffty, BG; Goldberg, S; Niemierko, A; Raad, RA; Oswald, MJ; Sullivan, T; Strom, EA; Powell, SN; Katz, A; Taghian, AG
MLA Citation
Floyd, SR, Buchholz, TA, Haffty, BG, Goldberg, S, Niemierko, A, Raad, RA, Oswald, MJ, Sullivan, T, Strom, EA, Powell, SN, Katz, A, and Taghian, AG. "Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger." International journal of radiation oncology, biology, physics 66.2 (October 2006): 358-364.
PMID
16887288
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
2
Publish Date
2006
Start Page
358
End Page
364
DOI
10.1016/j.ijrobp.2006.05.001

Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?

PURPOSE: To evaluate and quantify the effect of irradiated lung volume, radiation dose, and paclitaxel chemotherapy on the development of radiation pneumonitis (RP) in breast cancer patients with positive lymph nodes. METHODS AND MATERIALS: We previously reported the incidence of RP among 41 patients with breast cancer treated with radiotherapy (RT) and adjuvant paclitaxel-containing chemotherapy. We recorded the central lung distance, a measure of the extent of lung included in the RT volume, in these patients. We used this measure and the historical and observed rates of RP in our series to model the lung tolerance to RT in patients receiving chemotherapy (CHT) both with and without paclitaxel. To evaluate the risk factors for the development of RP, we performed a case-control study comparing paclitaxel-treated patients who developed RP with those who did not, and a second case-control study comparing patients receiving paclitaxel in addition to standard CHT/RT (n = 41) and controls receiving standard CHT/RT alone (n = 192). RESULTS: The actuarial rate of RP in the paclitaxel-treated group was 15.4% compared with 0.9% among breast cancer patients treated with RT and non-paclitaxel-containing CHT. Our mathematical model found that the effective lung tolerance for patients treated with paclitaxel was reduced by approximately 24%. No statistically significant difference was found with regard to the dose delivered to specific radiation fields, dose per fraction, central lung distance, or percentage of lung irradiated in the case-control study of paclitaxel-treated patients who developed RP compared with those who did not. In the comparison of 41 patients receiving RT and CHT with paclitaxel and 192 matched controls receiving RT and CHT without paclitaxel, the only significant differences identified were the more frequent use of a supraclavicular radiation field and a decrease in the RT lung dose among the paclitaxel-treated patients. This finding indicates that the major factor associated with development of RP was paclitaxel treatment. CONCLUSIONS: The use of paclitaxel chemotherapy and RT in the primary treatment of node-positive breast cancer is likely to increase the incidence of RP. In patients treated with paclitaxel, reducing the percentage of lung irradiated by 24% should reduce the risk of RP to 1%, according to our calculations of lung tolerance. Future clinical trials using combination CHT that includes paclitaxel and RT should carefully evaluate the incidence and severity of RP and should also accurately monitor the extent of lung included within the RT volume to develop safe guidelines for the delivery of what is becoming standard therapy for node-positive breast cancer.

Authors
Taghian, AG; Assaad, SI; Niemierko, A; Floyd, SR; Powell, SN
MLA Citation
Taghian, AG, Assaad, SI, Niemierko, A, Floyd, SR, and Powell, SN. "Is a reduction in radiation lung volume and dose necessary with paclitaxel chemotherapy for node-positive breast cancer?." International journal of radiation oncology, biology, physics 62.2 (June 2005): 386-391.
PMID
15890579
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
62
Issue
2
Publish Date
2005
Start Page
386
End Page
391
DOI
10.1016/j.ijrobp.2004.09.044

Plasma cell problems: Case 1. Disseminated cutaneous plasmacytomas treated with total skin electron radiotherapy.

Authors
Floyd, SR; Pantanowitz, L; McDermott, DF; Yannucci, J; Driver, JA; Stevenson, MA; Smith, BD; Wilson, LD; Richardson, PG
MLA Citation
Floyd, SR, Pantanowitz, L, McDermott, DF, Yannucci, J, Driver, JA, Stevenson, MA, Smith, BD, Wilson, LD, and Richardson, PG. "Plasma cell problems: Case 1. Disseminated cutaneous plasmacytomas treated with total skin electron radiotherapy." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 23.13 (May 2005): 3138-3140.
PMID
15860873
Source
epmc
Published In
Journal of Clinical Oncology
Volume
23
Issue
13
Publish Date
2005
Start Page
3138
End Page
3140
DOI
10.1200/jco.2005.05.175

Paraneoplastic stiff-person syndrome: no tumor progression over 5 years.

Authors
Schmierer, K; Grosse, P; De Camilli, P; Solimena, M; Floyd, S; Zschenderlein, R
MLA Citation
Schmierer, K, Grosse, P, De Camilli, P, Solimena, M, Floyd, S, and Zschenderlein, R. "Paraneoplastic stiff-person syndrome: no tumor progression over 5 years." Neurology 58.1 (January 2002): 148-.
PMID
11781426
Source
epmc
Published In
Neurology
Volume
58
Issue
1
Publish Date
2002
Start Page
148
DOI
10.1212/wnl.58.1.148

Generation of high curvature membranes mediated by direct endophilin bilayer interactions.

Endophilin 1 is a presynaptically enriched protein which binds the GTPase dynamin and the polyphosphoinositide phosphatase synptojanin. Perturbation of endophilin function in cell-free systems and in a living synapse has implicated endophilin in endocytic vesicle budding (Ringstad, N., H. Gad, P. Low, G. Di Paolo, L. Brodin, O. Shupliakov, and P. De Camilli. 1999. Neuron. 24:143-154; Schmidt, A., M. Wolde, C. Thiele, W. Fest, H. Kratzin, A.V. Podtelejnikov, W. Witke, W.B. Huttner, and H.D. Soling. 1999. Nature. 401:133-141; Gad, H., N. Ringstad, P. Low, O. Kjaerulff, J. Gustafsson, M. Wenk, G. Di Paolo, Y. Nemoto, J. Crun, M.H. Ellisman, et al. 2000. Neuron. 27:301-312). Here, we show that purified endophilin can directly bind and evaginate lipid bilayers into narrow tubules similar in diameter to the neck of a clathrin-coated bud, providing new insight into the mechanisms through which endophilin may participate in membrane deformation and vesicle budding. This property of endophilin is independent of its putative lysophosphatydic acid acyl transferase activity, is mediated by its NH2-terminal region, and requires an amino acid stretch homologous to a corresponding region in amphiphysin, a protein previously shown to have similar effects on lipid bilayers (Takei, K., V.I. Slepnev, V. Haucke, and P. De Camilli. 1999. Nat. Cell Biol. 1:33-39). Endophilin cooligomerizes with dynamin rings on lipid tubules and inhibits dynamin's GTP-dependent vesiculating activity. Endophilin B, a protein with homology to endophilin 1, partially localizes to the Golgi complex and also deforms lipid bilayers into tubules, underscoring a potential role of endophilin family members in diverse tubulovesicular membrane-trafficking events in the cell.

Authors
Farsad, K; Ringstad, N; Takei, K; Floyd, SR; Rose, K; De Camilli, P
MLA Citation
Farsad, K, Ringstad, N, Takei, K, Floyd, SR, Rose, K, and De Camilli, P. "Generation of high curvature membranes mediated by direct endophilin bilayer interactions." The Journal of cell biology 155.2 (October 15, 2001): 193-200.
PMID
11604418
Source
epmc
Published In
The Journal of Cell Biology
Volume
155
Issue
2
Publish Date
2001
Start Page
193
End Page
200
DOI
10.1083/jcb.200107075

A novel antineuronal antibody in a motor neuron syndrome associated with breast cancer.

A 72-year-old woman developed a lower motor neuron syndrome (MNS) 4 months before the appearance of breast cancer. Monoparesis progressed to quadriparesis despite high-dose IV immunoglobulins, plasma exchange, and azathioprine, and high-dose IV methylprednisolone. The patient improved only after the removal of the tumor. MRI demonstrated hyperintensities in the cervical spinal cord. The patient had antibodies that reacted with axonal initial segments and nodes of Ranvier. The findings suggest that in this patient lower MNS may be a paraneoplastic condition associated with breast cancer.

Authors
Ferracci, F; Fassetta, G; Butler, MH; Floyd, S; Solimena, M; De Camilli, P
MLA Citation
Ferracci, F, Fassetta, G, Butler, MH, Floyd, S, Solimena, M, and De Camilli, P. "A novel antineuronal antibody in a motor neuron syndrome associated with breast cancer." Neurology 53.4 (September 1999): 852-855.
PMID
10489053
Source
epmc
Published In
Neurology
Volume
53
Issue
4
Publish Date
1999
Start Page
852
End Page
855
DOI
10.1212/wnl.53.4.852

Endocytosis proteins and cancer: a potential link?

Recent studies have shown that a variety of proteins participate with clathrin and clathrin adaptors in receptor-mediated endocytosis. The genes encoding some of these proteins are targets of chromosomal rearrangements in human haematopoietic malignancies. In addition, abnormal expression or mutation of some endocytosis proteins has been reported in human cancers. This article discusses these observations and elaborates the potential mechanisms by which the abnormal expression of endocytosis proteins might participate in the biology of cancer.

Authors
Floyd, S; De Camilli, P
MLA Citation
Floyd, S, and De Camilli, P. "Endocytosis proteins and cancer: a potential link?." Trends in cell biology 8.8 (August 1998): 299-301. (Review)
PMID
9704404
Source
epmc
Published In
Trends in Cell Biology
Volume
8
Issue
8
Publish Date
1998
Start Page
299
End Page
301
DOI
10.1016/s0962-8924(98)01316-6

Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.

Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an alternatively spliced variant of neuronal amphiphysin I missing a 42 amino acid insert. Our study suggests a link between amphiphysin I expression in cancer and amphiphysin I autoimmunity. The enhanced expression of amphiphysin I in some forms of cancer supports the hypothesis that amphiphysin family members may play a role in the biology of cancer cells.

Authors
Floyd, S; Butler, MH; Cremona, O; David, C; Freyberg, Z; Zhang, X; Solimena, M; Tokunaga, A; Ishizu, H; Tsutsui, K; De Camilli, P
MLA Citation
Floyd, S, Butler, MH, Cremona, O, David, C, Freyberg, Z, Zhang, X, Solimena, M, Tokunaga, A, Ishizu, H, Tsutsui, K, and De Camilli, P. "Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer." Molecular medicine (Cambridge, Mass.) 4.1 (January 1998): 29-39.
PMID
9513187
Source
epmc
Published In
Molecular medicine (Cambridge, Mass.)
Volume
4
Issue
1
Publish Date
1998
Start Page
29
End Page
39
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