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Article: Metastasis-Directed Therapy in Prostate Cancer. Why, When, and How?

Phillips, Ryan M / Deek, Matthew P / Deweese, Theodore L / Tran, Phuoc T

2019 Volume 33, Issue 10

Abstract: Metastatic prostate cancer remains a life-limiting disease; while we have seen significant advances in systemic approaches which form the backbone of management, no curative paradigm yet exists. Metastasis-directed therapy (MDT) with stereotactic ... ...

Abstract	Metastatic prostate cancer remains a life-limiting disease; while we have seen significant advances in systemic approaches which form the backbone of management, no curative paradigm yet exists. Metastasis-directed therapy (MDT) with stereotactic ablative radiotherapy (SABR) has emerged as a promising complementary technique for the management of low-volume metastatic prostate cancer. Herein we will review the rationale, potential benefits, and practical considerations associated with this approach.
MeSH term(s)	Clinical Trials as Topic/statistics & numerical data ; Humans ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms/secondary ; Prostatic Neoplasms/surgery ; Radiosurgery/methods
Language	English
Publishing date	2019-10-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1067950-9
ISSN	0890-9091
ISSN	0890-9091
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Article ; Online: Examinations in Radiation Oncology: Listening, Learning, and Looking Forward Together.

Ennis, Ronald D / Movsas, Benjamin / Park, Catherine / Sandler, Howard M / Smith, Benjamin D / Wilson, Lynn / Deweese, Theodore L

International journal of radiation oncology, biology, physics

2019 Volume 106, Issue 1, Page(s) 29–31

MeSH term(s)	Certification ; Learning ; Physical Examination ; Radiation Oncology
Language	English
Publishing date	2019-10-21
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2019.10.012
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Article: Stereotactic radiation therapy combined with immunotherapy: augmenting the role of radiation in local and systemic treatment.

Sharabi, Andrew B / Tran, Phuoc T / Lim, Michael / Drake, Charles G / Deweese, Theodore L

Oncology (Williston Park, N.Y.)

2015 Volume 29, Issue 5, Page(s) 331–340

Abstract: Stereotactic radiosurgery and stereotactic body radiation therapy are two contemporary radiation modalities that can treat tumors in any area of the body using highly focused radiation. Recently, immunotherapy has established itself as a viable and ... ...

Abstract	Stereotactic radiosurgery and stereotactic body radiation therapy are two contemporary radiation modalities that can treat tumors in any area of the body using highly focused radiation. Recently, immunotherapy has established itself as a viable and powerful anticancer treatment. In this review we detail the rationale supporting a combination of immunotherapy and stereotactic radiation. Additionally, we discuss the evidence for the immune stimulatory effects of focused radiation and the role that radiation may play in enhancing the systemic treatment effects of immunotherapy.
MeSH term(s)	Combined Modality Therapy ; Glioma/therapy ; Humans ; Immunotherapy ; Lung Neoplasms/therapy ; Male ; Neoplasms/therapy ; Prostatic Neoplasms/therapy ; Radiosurgery
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1067950-9
ISSN	0890-9091
ISSN	0890-9091
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Article ; Online: Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen.

Sharabi, Andrew B / Nirschl, Christopher J / Kochel, Christina M / Nirschl, Thomas R / Francica, Brian J / Velarde, Esteban / Deweese, Theodore L / Drake, Charles G

Cancer immunology research

2015 Volume 3, Issue 4, Page(s) 345–355

Abstract: The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen- ... ...

Abstract	The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature of radiation-induced immune responses and elucidate potential mechanisms of synergy with immunotherapy. Here, we demonstrate the ability of stereotactic XRT to induce endogenous antigen-specific immune responses when it is combined with anti-PD-1 checkpoint blockade immunotherapy. Using the small animal radiation research platform (SARRP), image-guided stereotactic XRT delivered to B16-OVA melanoma or 4T1-HA breast carcinoma tumors resulted in the development of antigen-specific T cell- and B cell-mediated immune responses. These immune-stimulating effects of XRT were significantly increased when XRT was combined with either anti-PD-1 therapy or regulatory T cell (Treg) depletion, resulting in improved local tumor control. Phenotypic analyses of antigen-specific CD8 T cells revealed that XRT increased the percentage of antigen-experienced T cells and effector memory T cells. Mechanistically, we found that XRT upregulates tumor-associated antigen-MHC complexes, enhances antigen cross-presentation in the draining lymph node, and increases T-cell infiltration into tumors. These findings demonstrate the ability of XRT to prime an endogenous antigen-specific immune response and provide an additional mechanistic rationale for combining radiation with PD-1 blockade in the clinic.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Combined Modality Therapy ; Cross-Priming/immunology ; Female ; Immunologic Memory/immunology ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/immunology ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/therapy ; Melanoma, Experimental/immunology ; Melanoma, Experimental/therapy ; Mice, Knockout ; Programmed Cell Death 1 Receptor/immunology ; Radiosurgery/methods
Chemical Substances	Antigens, Neoplasm ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2015-04
Publishing country	United States
Document type	Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-14-0196
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Article ; Online: Neoadjuvant chemoradiation followed by interstitial prostate brachytherapy for synchronous prostate and rectal cancer.

Qiu, Haoming / Herman, Joseph M / Ahuja, Nita / Deweese, Theodore L / Song, Danny Y

Practical radiation oncology

2012 Volume 2, Issue 4, Page(s) e77–84

Abstract: Purpose: To describe outcomes with the use of neoadjuvant pelvic chemoradiation followed by prostate interstitial brachytherapy for the treatment of synchronous prostate and rectal cancers.: Methods and materials: An Internal Review Board approved ... ...

Abstract	Purpose: To describe outcomes with the use of neoadjuvant pelvic chemoradiation followed by prostate interstitial brachytherapy for the treatment of synchronous prostate and rectal cancers. Methods and materials: An Internal Review Board approved retrospective review was undertaken of 4 patients with synchronous prostate and rectal cancer treated between 2006 and 2008. Patients underwent pelvic chemoradiation followed by prostate brachytherapy, then low anterior resection of the rectum with diverting loop ileostomy and adjuvant chemotherapy. Follow-up evaluation included imaging and laboratory analysis of cancer markers in addition to routine interval history and physical examination. Results: At 38-62 months postdiagnosis (24-53 months post-treatment), 6 of 8 cancers remained without evidence of relapse. One patient had rising carcinoembryonic antigen levels but no clinically evident rectal cancer relapse; another developed bony metastasis of his high-risk prostate cancer. Three patients experienced grade 1-2 treatment-related toxicity; one patient had grade 3 gastrointestinal toxicity from radiation and surgery, which precluded his receiving adjuvant chemotherapy and ileostomy reversal. Conclusions: Chemoradiation followed by prostate brachytherapy, surgery, and adjuvant chemotherapy may be utilized to manage patients with synchronous prostate and rectal cancers.
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Journal Article
ISSN	1879-8519
ISSN (online)	1879-8519
DOI	10.1016/j.prro.2011.11.001
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Article: Safety strategies in an academic radiation oncology department and recommendations for action.

Terezakis, Stephanie A / Pronovost, Peter / Harris, Kendra / Deweese, Theodore / Ford, Eric

Joint Commission journal on quality and patient safety

2011 Volume 37, Issue 7, Page(s) 291–299

Abstract: Background: Safety initiatives in the United States continue to work on providing guidance as to how the average practitioner might make patients safer in the face of the complex process by which radiation therapy (RT), an essential treatment used in ... ...

Abstract	Background: Safety initiatives in the United States continue to work on providing guidance as to how the average practitioner might make patients safer in the face of the complex process by which radiation therapy (RT), an essential treatment used in the management of many patients with cancer, is prepared and delivered. Quality control measures can uncover certain specific errors such as machine dose miscalibration or misalignments of the patient in the radiation treatment beam. However, they are less effective at uncovering less common errors that can occur anywhere along the treatment planning and delivery process, and even when the process is functioning as intended, errors still occur. PRIORITIZING RISKS AND IMPLEMENTING RISK-REDUCTION STRATEGIES: Activities undertaken at the radiation oncology department at the Johns Hopkins Hospital (Baltimore) include Failure Mode and Effects Analysis (FMEA), risk-reduction interventions, and voluntary error and near-miss reporting systems. A visual process map portrayed 269 RT steps occurring among four subprocesses-including consult, simulation, treatment planning, and treatment delivery. Two FMEAs revealed 127 and 159 possible failure modes, respectively. Risk-reduction interventions for 15 "top-ranked" failure modes were implemented. Since the error and near-miss reporting system's implementation in the department in 2007, 253 events have been logged. However, the system may be insufficient for radiation oncology, for which a greater level of practice-specific information is required to fully understand each event. Conclusions: The "basic science" of radiation treatment has received considerable support and attention in developing novel therapies to benefit patients. The time has come to apply the same focus and resources to ensuring that patients safely receive the maximal benefits possible.
MeSH term(s)	Documentation/methods ; Humans ; Medical Errors/prevention & control ; Oncology Service, Hospital/organization & administration ; Quality Assurance, Health Care/organization & administration ; Radiation Oncology/organization & administration ; Risk Management/organization & administration ; Risk Reduction Behavior ; Safety Management/organization & administration ; Workflow
Language	English
Publishing date	2011-08-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1189890-2
ISSN	1938-131X ; 1549-425X ; 1553-7250 ; 1070-3241 ; 1549-3741
ISSN (online)	1938-131X ; 1549-425X
ISSN	1553-7250 ; 1070-3241 ; 1549-3741
DOI	10.1016/s1553-7250(11)37037-7
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Article: Radiation therapy for prostate cancer: the role for dose escalation.

Swartz, Michael J / Janson, Kristin / Deweese, Theodore L / Song, Danny Y

Comprehensive therapy

2007 Volume 33, Issue 4, Page(s) 216–222

Abstract: Recent technological advances in radiation treatment delivery have allowed relatively higher doses of radiation to be delivered safely to the prostate. Emerging data suggest improvements in disease control with higher doses of radiation in subsets of ... ...

Abstract	Recent technological advances in radiation treatment delivery have allowed relatively higher doses of radiation to be delivered safely to the prostate. Emerging data suggest improvements in disease control with higher doses of radiation in subsets of patients with prostate cancer.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Brachytherapy ; Combined Modality Therapy ; Dose-Response Relationship, Radiation ; Humans ; Male ; Prostatic Neoplasms/radiotherapy ; Prostatic Neoplasms/therapy ; Radiotherapy Dosage ; Risk Assessment
Chemical Substances	Angiogenesis Inhibitors
Language	English
Publishing date	2007-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	752013-x
ISSN	1559-1190 ; 0098-8243
ISSN (online)	1559-1190
ISSN	0098-8243
DOI	10.1007/s12019-007-8014-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1329: Show issues

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Article ; Online: Accuracy of marketing claims by providers of stereotactic radiation therapy.

Narang, Amol K / Lam, Edwin / Makary, Martin A / Deweese, Theodore L / Pawlik, Timothy M / Pronovost, Peter J / Herman, Joseph M

Journal of oncology practice

2013 Volume 9, Issue 1, Page(s) 57–62

Abstract: Purpose: Direct-to-consumer advertising by industry has been criticized for encouraging overuse of unproven therapies, but advertising by health care providers has not been as carefully scrutinized. Stereotactic radiation therapy is an emerging ... ...

Abstract	Purpose: Direct-to-consumer advertising by industry has been criticized for encouraging overuse of unproven therapies, but advertising by health care providers has not been as carefully scrutinized. Stereotactic radiation therapy is an emerging technology that has sparked controversy regarding the marketing campaigns of some manufacturers. Given that this technology is also being heavily advertised on the Web sites of health care providers, the accuracy of providers' marketing claims should be rigorously evaluated. Methods: We reviewed the Web sites of all U.S. hospitals and private practices that provide stereotactic radiation using two leading brands of stereotactic radiosurgery technology. Centers were identified by using data from the manufacturers. Centers without Web sites were excluded. The final study population consisted of 212 centers with online advertisements for stereotactic radiation. Web sites were evaluated for advertisements that were inconsistent with advertising guidelines provided by the American Medical Association. Results: Most centers (76%) had individual pages dedicated to the marketing of their brand of stereotactic technology that frequently contained manufacturer-authored images (50%) or text (55%). Advertising for the treatment of tumors that have not been endorsed by professional societies was present on 66% of Web sites. Centers commonly claimed improved survival (22%), disease control (20%), quality of life (17%), and toxicity (43%) with stereotactic radiation. Although 40% of Web sites championed the center's regional expertise in delivering stereotactic treatments, only 15% of Web sites provided data to support their claims. Conclusion: Provider advertisements for stereotactic radiation were prominent and aggressive. Further investigation of provider advertising, its effects on quality of care, and potential oversight mechanisms is needed.
MeSH term(s)	Hospitals/statistics & numerical data ; Humans ; Internet ; Marketing ; Neoplasms/radiotherapy ; Physicians ; Private Practice/statistics & numerical data ; Radiosurgery ; United States
Language	English
Publishing date	2013-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2236338-5
ISSN	1935-469X ; 1554-7477
ISSN (online)	1935-469X
ISSN	1554-7477
DOI	10.1200/JOP.2012.000693
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Article ; Online: Method to reduce non-specific tissue heating of small animals in solenoid coils.

Kumar, Ananda / Attaluri, Anilchandra / Mallipudi, Rajiv / Cornejo, Christine / Bordelon, David / Armour, Michael / Morua, Katherine / Deweese, Theodore L / Ivkov, Robert

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

2013 Volume 29, Issue 2, Page(s) 106–120

Abstract: Purpose: Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus ... ...

Abstract	Purpose: Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. Materials and methods: Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50 kA/m and frequency of 160 kHz. Results: Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. Conclusions: These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs.
MeSH term(s)	Animals ; Body Temperature Regulation ; Cold Temperature ; Computer Simulation ; Equipment Design ; Heating/adverse effects ; Hyperthermia, Induced/instrumentation ; Magnetic Fields ; Male ; Mice ; Mice, Inbred BALB C ; Phantoms, Imaging ; Thermal Conductivity ; Water
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2013-02-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632526-9
ISSN	1464-5157 ; 0265-6736
ISSN (online)	1464-5157
ISSN	0265-6736
DOI	10.3109/02656736.2013.764023
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Article ; Online: Targeting aberrant DNA double-strand break repair in triple-negative breast cancer with alpha-particle emitter radiolabeled anti-EGFR antibody.

Song, Hong / Hedayati, Mohammad / Hobbs, Robert F / Shao, Chunbo / Bruchertseifer, Frank / Morgenstern, Alfred / Deweese, Theodore L / Sgouros, George

Molecular cancer therapeutics

2013 Volume 12, Issue 10, Page(s) 2043–2054

Abstract: The higher potential efficacy of alpha-particle radiopharmaceutical therapy lies in the 3- to 8-fold greater relative biological effectiveness (RBE) of alpha particles relative to photon or beta-particle radiation. This greater RBE, however, also applies ...

Abstract	The higher potential efficacy of alpha-particle radiopharmaceutical therapy lies in the 3- to 8-fold greater relative biological effectiveness (RBE) of alpha particles relative to photon or beta-particle radiation. This greater RBE, however, also applies to normal tissue, thereby reducing the potential advantage of high RBE. As alpha particles typically cause DNA double-strand breaks (DSB), targeting tumors that are defective in DSB repair effectively increases the RBE, yielding a secondary, RBE-based differentiation between tumor and normal tissue that is complementary to conventional, receptor-mediated tumor targeting. In some triple-negative breast cancers (TNBC; ER(-)/PR(-)/HER-2(-)), germline mutation in BRCA-1, a key gene in homologous recombination DSB repair, predisposes patients to early onset of breast cancer. These patients have few treatment options once the cancer has metastasized. In this study, we investigated the efficacy of alpha-particle emitter, (213)Bi-labeled anti-EGF receptor antibody, cetuximab, in BRCA-1-defective TNBC. (213)Bi-cetuximab was found to be significantly more effective in the BRCA-1-mutated TNBC cell line HCC1937 than BRCA-1-competent TNBC cell MDA-MB-231. siRNA knockdown of BRCA-1 or DNA-dependent protein kinase, catalytic subunit (DNA-PKcs), a key gene in non-homologous end-joining DSB repair pathway, also sensitized TNBC cells to (213)Bi-cetuximab. Furthermore, the small-molecule inhibitor of DNA-PKcs, NU7441, sensitized BRCA-1-competent TNBC cells to alpha-particle radiation. Immunofluorescent staining of γ-H2AX foci and comet assay confirmed that enhanced RBE is caused by impaired DSB repair. These data offer a novel strategy for enhancing conventional receptor-mediated targeting with an additional, potentially synergistic radiobiological targeting that could be applied to TNBC.
MeSH term(s)	Alpha Particles ; Antibodies, Monoclonal, Humanized/administration & dosage ; BRCA1 Protein/genetics ; Bismuth/administration & dosage ; Cell Line, Tumor ; Cetuximab ; DNA Breaks, Double-Stranded/drug effects ; DNA End-Joining Repair/drug effects ; DNA End-Joining Repair/immunology ; DNA Repair/drug effects ; DNA Repair/genetics ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/immunology ; Female ; Histones/metabolism ; Humans ; Radioisotopes/administration & dosage ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/immunology
Chemical Substances	Antibodies, Monoclonal, Humanized ; BRCA1 Protein ; BRCA1 protein, human ; H2AX protein, human ; Histones ; Radioisotopes ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Cetuximab (PQX0D8J21J) ; Bismuth (U015TT5I8H)
Language	English
Publishing date	2013-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-13-0108
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