220 results on '"Bhadrasain Vikram"'
Search Results
2. Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?
- Author
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Sandra Demaria, C Norman Coleman, Jonathan Schoenfeld, Arta Monjazeb, Samir Khleif, Seema Gupta, Andrew Sikora, Zachary Morris, Chandan Guha, Stephen Shiao, Silvia Chiara Formenti, Bhadrasain Vikram, and Mansoor M Ahmed
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Recent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation’s ability to promote immune responses to tumors. Other novel delivery options may also affect immune responses, including T-cell activation and tumor-antigen presentation changes. However, there is limited understanding of the immunological impact of hypofractionated and unique multifractionated radiotherapy regimens, as these observations are relatively recent. Hence, these differences in radiotherapy fractionation result in distinct immune-modulatory effects. Radiation oncologists and immunologists convened a virtual consensus discussion to identify current deficiencies, challenges, pitfalls and critical gaps when combining radiotherapy with immunotherapy and making recommendations to the field and advise National Cancer Institute on new directions and initiatives that will help further development of these two fields.This commentary aims to raise the awareness of this complexity so that the need to study radiation dose, fractionation, type and volume is understood and valued by the immuno-oncology research community. Divergence of approaches and findings between preclinical studies and clinical trials highlights the need for evaluating the design of future clinical studies with particular emphasis on radiation dose and fractionation, immune biomarkers and selecting appropriate end points for combination radiation/immune modulator trials, recognizing that direct effect on the tumor and potential abscopal effect may well be different. Similarly, preclinical studies should be designed as much as possible to model the intended clinical setting. This article describes a conceptual framework for testing different radiation therapy regimens as separate models of how radiation itself functions as an immunomodulatory ‘drug’ to provide alternatives to the widely adopted ‘one-size-fits-all’ strategy of frequently used 8 Gy×3 regimens immunomodulation.
- Published
- 2021
- Full Text
- View/download PDF
3. Radiation Oncology in the 21st Century: Prospective Randomized Trials That Changed Practice… or Didn’t!
- Author
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Kaveh Zakeri, C. Norman Coleman, and Bhadrasain Vikram
- Subjects
randomized trials ,radiation oncology ,survival ,local control ,adverse events ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In a two-part article published in 2009, we discussed the limitations of conventional radiation therapy, the challenges of studying new technologies in radiation oncology, and summarized the state-of-the science for various malignancies (1, 2). Here, we summarize some of the most important prospective, randomized trials that during the intervening years have attempted to improve the tumor control and/or decrease the adverse effects of radiation therapy. For consistency, we have focused here on the null and alternate hypotheses as articulated by the investigators at the onset of each trial, since the outcome of the investigational treatment should be considered clinically significant only if the null hypothesis was rejected. The readers (and patients) are of course free to make their own judgments about the clinical significance of the results when the null hypothesis was not rejected.
- Published
- 2018
- Full Text
- View/download PDF
4. Editorial: Data Based Radiation Oncology—Design of Clinical Trials
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Kerstin Anne Kessel, Anne W. M. Lee, Søren M. Bentzen, Bhadrasain Vikram, Fridtjof Nüsslin, and Stephanie E. Combs
- Subjects
clinical trials ,data collection ,radiation oncology ,clinical study design ,study management ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2018
- Full Text
- View/download PDF
5. Establishing global health cancer care partnerships across common ground: bridging nuclear security, equitable access, education, outreach, and mentorship
- Author
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C Norman Coleman, MD, Silvia C Formenti, MD, Nelson Chao, MD, Surbhi Grover, MD, Danielle Rodin, MD, Daniel G Petereit, MD, Bhadrasain Vikram, MD, David A Pistenmaa, MD, Majid Mohiuddin, MD, Tim R Williams, MD, Nina Wendling, PhD, Lawrence Roth, MBA, Mary Gospodarowicz, MD, and D Jaffray, PhD
- Subjects
Public aspects of medicine ,RA1-1270 - Published
- 2016
- Full Text
- View/download PDF
6. Overview of the First NRG Oncology–National Cancer Institute Workshop on Dosimetry of Systemic Radiopharmaceutical Therapy
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Roncali, Emilie, Capala, Jacek, Benedict, Stanley H, Akabani, Gamal, Bednarz, Bryan, Bhadrasain, Vikram, Bolch, Wesley E, Buchsbaum, Jeffrey C, Coleman, Norman C, Dewaraja, Yuni K, Frey, Eric, Ghaly, Michael, Grudzinski, Joseph, Hobbs, Robert F, Howell, Roger W, Humm, John L, Kunos, Charles A, Larson, Steve, Lin, Frank I, Madsen, Mark, Mirzadeh, Saed, Morse, David, Pryma, Daniel, Sgouros, George, St James, Sara, Wahl, Richard L, Xiao, Ying, Zanzonico, Pat, and Zukotynski, Katherine
- Subjects
Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,Good Health and Well Being ,National Cancer Institute (U.S.) ,Neoplasms ,Radiometry ,United States ,radiopharmaceutical therapy ,targeted radionuclide therapy ,dosimetry ,microdosimetry ,cellular dosimetry ,MIRD ,Clinical Sciences ,Nuclear Medicine & Medical Imaging - Abstract
In 2018, the National Cancer Institute and NRG Oncology partnered for the first time to host a joint workshop on systemic radiopharmaceutical therapy (RPT) to specifically address dosimetry issues and strategies for future clinical trials. The workshop focused on current dosimetric approaches for clinical trials, strategies under development that would optimize dose reporting, and future desired or optimized approaches for novel emerging radionuclides and carriers in development. In this article, we review the main approaches that are applied clinically to calculate the absorbed dose. These include absorbed doses calculated over a variety of spatial scales, including whole body, organ, suborgan, and voxel, the last 3 of which are achievable within the MIRD schema (S value) and can be calculated with analytic methods or Monte Carlo methods, the latter in most circumstances. This article will also contrast currently available methods and tools with those used in the past, to propose a pathway whereby dosimetry helps the field by optimizing the biologic effect of the treatment and trial design in the drug approval process to reduce financial and logistical costs. We also briefly discuss the dosimetric equivalent of biomarkers to help bring a precision medicine approach to RPT implementation when merited by evidence collected during early-phase trial investigations. Advances in the methodology and related tools have made dosimetry the optimum biomarker for RPT.
- Published
- 2021
7. Tumor Heterogeneity Research and Innovation in Biologically Based Radiation Therapy From the National Cancer Institute Radiation Research Program Portfolio
- Author
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Jeffrey C. Buchsbaum, Michael G. Espey, Ceferino Obcemea, Jacek Capala, Mansoor Ahmed, Pataje G. Prasanna, Bhadrasain Vikram, Julie A. Hong, Beverly Teicher, Molykutty J. Aryankalayil, Michelle A. Bylicky, and C. Norman Coleman
- Subjects
Comments and Controversies ,Cancer Research ,Oncology ,Neoplasms ,Humans ,National Cancer Institute (U.S.) ,United States - Published
- 2023
8. Overview and Lessons From the Preclinical Chemoradiotherapy Testing Consortium
- Author
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Michael Graham Espey, Bhadrasain Vikram, Eric J. Bernhard, Jeffrey C. Buchsbaum, and C. Norman Coleman
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Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Standard treatment ,Cancer ,Antineoplastic Agents ,Chemoradiotherapy ,medicine.disease ,Preclinical data ,Clinical trial ,Combined modality ,Oncology ,Cancer Therapy Evaluation Program ,Neoplasms ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Head and neck ,business - Abstract
Purpose: In the current molecular-targeted cancer treatment era, many new agents are being developed so that optimizing therapy with a combination of radiation and drugs is complex. The use of emerging laboratory technologies to further biological understanding of drug-radiation mechanisms of action will enhance the efficiency of the progression from preclinical studies to clinical trials. In 2017, the National Cancer Institute (NCI) solicited proposals through PAR 16-111 to conduct preclinical research combining targeted anticancer agents in the Cancer Therapy Evaluation Program's portfolio with chemoradiation. Methods and Materials The Preclinical Chemo-Radiotherapy Testing Consortium (PCRTC) was formed with 4 U01 programs supported to generate validated high-quality preclinical data on the effects of molecular therapeutics when added to standard-of-care therapies with a concentration on cancers of the pancreas, lung, head and neck, gastrointestinal tract, and brain. Results The PCRTC provides a rational basis for prioritizing NCI-supported investigational new drugs or agents most likely to have clinical activity with chemoradiotherapy and accelerate the pace at which combined modality treatments with greater efficacy are identified and incorporated into standard treatment practices. Conclusions Herein, we introduce and summarize the course of the PCRTC to date and report 3 preliminary observations from the consortium's work to date.
- Published
- 2021
9. Neutron Capture Therapy: The Promise of Novel Agents and Medical Facility-Based Neutron Sources
- Author
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Jacek Capala, Julie A. Hong, Bhadrasain Vikram, and C. Norman Coleman
- Subjects
Pharmacology ,Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2023
10. The NCI Glioblastoma Therapeutics Network (GTN)
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Suzanne Forry, Leah Hubbard, Michael G Espey, Bhadrasain Vikram, Bhupinder Mann, Abdul Tawab-Amiri, and Toby Hecht
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Cancer Research ,Oncology ,Neurology (clinical) - Published
- 2022
11. Pathways for Recruiting and Retaining Women and Underrepresented Minority Clinicians and Physician Scientists Into the Radiation Oncology Workforce: A Summary of the 2019 ASTRO/NCI Diversity Symposium Session at the ASTRO Annual Meeting
- Author
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Freddy E. Escorcia, Raymond B. Mailhot Vega, Curtiland Deville, Gita Suneja, Joel S. Greenberger, Alexander Spektor, Malika Siker, Bhadrasain Vikram, Aparna H. Kesarwala, Malcolm D. Mattes, and Colleen A. Lawton
- Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine ,Medical education ,business.industry ,lcsh:R895-920 ,MEDLINE ,Brief Opinion ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Health equity ,030218 nuclear medicine & medical imaging ,Unmet needs ,03 medical and health sciences ,0302 clinical medicine ,Mentorship ,Oncology ,030220 oncology & carcinogenesis ,Underrepresented Minority ,Workforce ,Radiation oncology ,Medicine ,Radiology, Nuclear Medicine and imaging ,business - Abstract
Diversifying the radiation oncology workforce is an urgent and unmet need. During the American Society of Radiation Oncology (ASTRO) 2019 Annual Meeting, ASTRO's Committee on Health Equity, Diversity, and Inclusion (CHEDI) and the National Cancer Institute (NCI) collaborated on the ASTRO-NCI Diversity Symposium, entitled ''Pathways for Recruiting and Retaining Women and Underrepresented Minority Clinicians and Physician Scientists Into the Radiation Oncology Workforce.'' Herein, we summarize the presented data and personal anecdotes with the goal of raising awareness of ongoing and future initiatives to improve recruitment and retention of underrepesented groups to radiation oncology. Common themes include the pivotal role of mentorship and standardized institutional practices – such as protected time and pay parity – as critical to achieving a more diverse and inclusive workplace.
- Published
- 2020
12. Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy
- Author
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Oleg Belyakov, Charles L. Limoli, Sylvia C. Formenti, Mack Roach, Mansoor M. Ahmed, Robert J. Griffin, Charles B. Simone, Quynh-Thu Le, Shalom Kalnicki, Anand Mahadevan, Bhadrasain Vikram, Douglas R. Spitz, Beatriz E. Amendola, Søren M. Bentzen, Pantaleo Romanelli, Karl T. Butterworth, Mohammed Mohiuddin, Mariangela Massaccesi, James S. Welsh, Sha Chang, Marie-Catherine Vozenin, N.A. Mayr, May Abdel-Wahab, Majid M. Mohiuddin, Kristoffer Petersson, James W. Snider, C. Norman Coleman, William F. Regine, Chandan Guha, Billy W. Loo, Ceferino Obcemea, Valentin Djonov, Eli Glatstein, P.G. Maxim, and Xiaodong Wu
- Subjects
Cancer Research ,medicine.medical_specialty ,Fractionated radiotherapy ,medicine.medical_treatment ,Radiation Dosage ,Radiosurgery ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Fractionated radiation ,Clinical Trials as Topic ,Radiation ,Radiotherapy ,business.industry ,Clinical trial ,Radiation therapy ,Clinical Practice ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Dose Fractionation, Radiation ,Dose rate ,business - Abstract
The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.
- Published
- 2020
13. Moving Forward in the Next Decade: Radiation Oncology Sciences for Patient-Centered Cancer Care
- Author
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Jacek Capala, Bhadrasain Vikram, Pataje G. S. Prasanna, Jeffrey C. Buchsbaum, C. Norman Coleman, Ceferino Obcemea, Julie A Hong, Mansoor M. Ahmed, and Michael Graham Espey
- Subjects
0301 basic medicine ,Big Data ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Big data ,Disease ,Radiation Tolerance ,03 medical and health sciences ,0302 clinical medicine ,Artificial Intelligence ,Neoplasms ,Patient-Centered Care ,Research Support as Topic ,Radiation oncology ,Global health ,Medicine ,Humans ,Medical physics ,Clinical Trials as Topic ,Radiotherapy ,business.industry ,Research ,Cancer ,Radiobiology ,Hyperthermia, Induced ,Neutron Capture Therapy ,medicine.disease ,Health equity ,Radiation therapy ,030104 developmental biology ,Workflow ,Oncology ,Photochemotherapy ,030220 oncology & carcinogenesis ,Commentary ,Radiation Oncology ,Radiopharmaceuticals ,business ,AcademicSubjects/MED00010 ,Relative Biological Effectiveness - Abstract
In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of “big data” and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal “focused biology.” Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.
- Published
- 2021
14. Enhancing Career Paths for Tomorrow's Radiation Oncologists
- Author
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Kavita V. Dharmarajan, Mary Gospodarowicz, Andrew D. Trister, Clifton D. Fuller, J.M. Longo, Neha Vapiwala, Joshua Jones, Danielle Rodin, John D. Boice, Reid F. Thompson, Joel W. Goldwein, Joanne B. Weidhaas, C. Norman Coleman, Paul Okunieff, Ronald D. Ennis, James A. Hayman, Alan H. Epstein, Daniel G. Petereit, Mei Ling Yap, Charles R. Thomas, Bhadrasain Vikram, Anthony L. Zietman, May Abdel-Wahab, Jeffrey C. Buchsbaum, Silvia C. Formenti, Lawrence N. Shulman, Mary Helen Barcellos-Hoff, Patrick A. Kupelian, Timur Mitin, Surbhi Grover, and Margaret A. Tucker
- Subjects
Cancer Research ,Palliative care ,MEDLINE ,Global Health ,Health informatics ,Nursing ,Global health ,Humans ,Medicine ,Industrial Development ,Radiology, Nuclear Medicine and imaging ,Medical Informatics Applications ,Biology ,Health policy ,Radiation ,Extramural ,business.industry ,Health Policy ,Palliative Care ,Radiation Oncologists ,United States ,Career Mobility ,Oncology ,Rural Health Services ,Diffusion of Innovation ,Radioactive Hazard Release ,business ,Medical Informatics ,Forecasting - Published
- 2019
15. The Use of Quantitative Imaging in Radiation Oncology: A Quantitative Imaging Network (QIN) Perspective
- Author
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Lori Henderson, Michael A. Jacobs, Nola M. Hylton, Paul E. Kinahan, Elizabeth R. Gerstner, Hui-Kuo Shu, Lawrence H. Schwartz, David A. Jaffray, Bhadrasain Vikram, Philippe Lambin, Thomas J. Dilling, Hannah M. Linden, Brenda F. Kurland, Lubomir M. Hadjiiski, Robert H. Press, Ella F. Jones, Edward Taylor, Matthias Holdhoff, Robert J. Nordstrom, Richard L. Wahl, James M. Mountz, John M. Buatti, Karen A. Kurdziel, Daniel L. Rubin, David A. Mankoff, and Hyunsuk Shim
- Subjects
Cancer Research ,Magnetic Resonance Spectroscopy ,STANDARDIZED UPTAKE VALUE ,medicine.medical_treatment ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Neoplasms ,ADVANCED RECTAL-CANCER ,Tomography ,Cancer ,LOCALIZED PROSTATE-CANCER ,Radiation ,MAGNETIC-RESONANCE-SPECTROSCOPY ,Magnetic Resonance Imaging ,X-Ray Computed ,3. Good health ,Other Physical Sciences ,Oncology ,030220 oncology & carcinogenesis ,ENHANCED COMPUTED-TOMOGRAPHY ,NEWLY-DIAGNOSED GLIOBLASTOMA ,medicine.medical_specialty ,Quantitative imaging ,CELL LUNG-CANCER ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Oncology and Carcinogenesis ,Context (language use) ,Article ,03 medical and health sciences ,POSITRON-EMISSION-TOMOGRAPHY ,Clinical Research ,Radiation oncology ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Oncology & Carcinogenesis ,External beam radiotherapy ,Modalities ,business.industry ,Perspective (graphical) ,Clinical trial ,Radiation therapy ,Good Health and Well Being ,EXTERNAL-BEAM RADIOTHERAPY ,Positron-Emission Tomography ,DIFFUSION-WEIGHTED MRI ,Radiation Oncology ,Tumor Hypoxia ,Tomography, X-Ray Computed ,business - Abstract
Modern radiation therapy is delivered with great precision, in part by relying on high-resolution multi-dimensional anatomical imaging to define targets in space and time. The development of quantitative imaging (QI) modalities capable of monitoring biologic parameters has the potential to provide deeper insight into tumor biology and facilitate more personalized clinical decision-making. The Quantitative Imaging Network (QIN) was established by the National Cancer Institute (NCI) to advance and validate these QI modalities in the context of oncology clinical trials, emphasizing the great clinical need for this technology. In particular, the QIN has significant interest in the application of QI to widen the therapeutic window of radiation therapy. QI modalities have great promise in radiation oncology and will help address significant clinical needs including finer prognostication, more specific target delineation, reduction of normal tissue toxicity, identification of radioresistant disease, and clearer interpretation of treatment response. Patient-specific quantitative information is being incorporated into radiation treatment design in ways such as dose escalation and adaptive replanning, with the intent of improving outcomes while lessening treatment morbidities. This review discusses the current vision of the QIN, current areas of investigation, and how it hopes to enhance the integration of QI into the practice of radiation oncology.
- Published
- 2018
16. Radiation dose and fraction in immunotherapy: one-size regimen does not fit all settings, so how does one choose?
- Author
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Mansoor M. Ahmed, Zachary S. Morris, Bhadrasain Vikram, Andrew G. Sikora, Seema Gupta, C. Norman Coleman, Jonathan D. Schoenfeld, Arta M. Monjazeb, Chandan Guha, Samir N. Khleif, Stephen L. Shiao, Marka R. Crittenden, Silvia C. Formenti, and Sandra Demaria
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Review ,Ionizing radiation ,0302 clinical medicine ,Risk Factors ,Neoplasms ,Tumor Microenvironment ,Immunology and Allergy ,Dose Fractionation ,RC254-282 ,Cancer ,Radiation ,clinical trials as topic ,Abscopal effect ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Combined Modality Therapy ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,immunotherapy ,Immunotherapy ,Patient Safety ,medicine.medical_specialty ,Immunology ,Clinical Decision-Making ,Radiation Dosage ,Risk Assessment ,Vaccine Related ,03 medical and health sciences ,Clinical Research ,medicine ,Animals ,Humans ,Medical physics ,radiotherapy ,Pharmacology ,business.industry ,Radiation dose ,medicine.disease ,Radiation therapy ,Clinical trial ,Regimen ,030104 developmental biology ,Immunization ,Dose Fractionation, Radiation ,business - Abstract
Recent evidence indicates that ionizing radiation can enhance immune responses to tumors. Advances in radiation delivery techniques allow hypofractionated delivery of conformal radiotherapy. Hypofractionation or other modifications of standard fractionation may improve radiation’s ability to promote immune responses to tumors. Other novel delivery options may also affect immune responses, including T-cell activation and tumor-antigen presentation changes. However, there is limited understanding of the immunological impact of hypofractionated and unique multifractionated radiotherapy regimens, as these observations are relatively recent. Hence, these differences in radiotherapy fractionation result in distinct immune-modulatory effects. Radiation oncologists and immunologists convened a virtual consensus discussion to identify current deficiencies, challenges, pitfalls and critical gaps when combining radiotherapy with immunotherapy and making recommendations to the field and advise National Cancer Institute on new directions and initiatives that will help further development of these two fields.This commentary aims to raise the awareness of this complexity so that the need to study radiation dose, fractionation, type and volume is understood and valued by the immuno-oncology research community. Divergence of approaches and findings between preclinical studies and clinical trials highlights the need for evaluating the design of future clinical studies with particular emphasis on radiation dose and fractionation, immune biomarkers and selecting appropriate end points for combination radiation/immune modulator trials, recognizing that direct effect on the tumor and potential abscopal effect may well be different. Similarly, preclinical studies should be designed as much as possible to model the intended clinical setting. This article describes a conceptual framework for testing different radiation therapy regimens as separate models of how radiation itself functions as an immunomodulatory ‘drug’ to provide alternatives to the widely adopted ‘one-size-fits-all’ strategy of frequently used 8 Gy×3 regimens immunomodulation.
- Published
- 2021
17. NCI support for pediatric radiation therapy: Past, present, and future
- Author
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Jeffrey C. Buchsbaum and Bhadrasain Vikram
- Subjects
medicine.medical_specialty ,Biomedical Research ,Radiotherapy ,business.industry ,medicine.medical_treatment ,MEDLINE ,Hematology ,Funding Mechanism ,National Cancer Institute (U.S.) ,United States ,Radiation therapy ,Oncology ,Research Support as Topic ,Pediatrics, Perinatology and Child Health ,Radiation oncology ,medicine ,Humans ,Medical physics ,business - Published
- 2020
18. Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?
- Author
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Bhadrasain Vikram, Dale J. Hu, Mansoor M. Ahmed, Ralph R. Weichselbaum, David G. Kirsch, Andrea L. DiCarlo, Silvia C. Formenti, Gayle E. Woloschak, Kathryn D. Held, Chandan Guha, C. Norman Coleman, Arnab Chakravarti, Dörthe Schaue, William H. McBride, Jeffrey C. Buchsbaum, Sunil Krishnan, Pataje G. S. Prasanna, Brian Marples, Wolfgang W. Leitner, Francis A. Cucinotta, Mohammad K. Khan, Shahin Rafii, Julie M. Sullivan, Elad Sharon, and Minesh P. Mehta
- Subjects
Risk ,medicine.medical_specialty ,Radiobiology ,Coronavirus disease 2019 (COVID-19) ,medicine.medical_treatment ,Pneumonia, Viral ,Biophysics ,MEDLINE ,Radiation Dosage ,Article ,030218 nuclear medicine & medical imaging ,law.invention ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Radiation oncology ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Pandemics ,Clinical Trials as Topic ,Radiation ,business.industry ,COVID-19 ,Radiotherapy Dosage ,Radiation therapy ,030220 oncology & carcinogenesis ,Low Dose Radiation Therapy ,Radiation protection ,business ,Coronavirus Infections - Abstract
The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.
- Published
- 2020
19. Potential Molecular Targets in the Setting of Chemoradiation for Esophageal Malignancies
- Author
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Anil K. Rustgi, Terence M. Williams, Geoffrey Liu, Wael El-Rifai, Eric D. Miller, Rosemary Wong, Mansoor M. Ahmed, Bhadrasain Vikram, Michael G. Haddock, Mutlay Sayan, Pataje G. S. Prasanna, Steven H. Lin, Norman Coleman, David H. Ilson, Salma K. Jabbour, Charles A. Kunos, Daniel S. Jamorabo, Jaffer A. Ajani, and Andrew C. Chang
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Commentaries ,medicine ,Carcinoma ,Humans ,030304 developmental biology ,Curative intent ,0303 health sciences ,Gene targets ,business.industry ,Distant relapse ,Cancer ,Chemoradiotherapy ,Esophageal cancer ,medicine.disease ,Disease control ,Combined Modality Therapy ,030220 oncology & carcinogenesis ,Molecular targets ,Carcinoma, Squamous Cell ,Neoplasm Recurrence, Local ,business - Abstract
Although the development of effective combined chemoradiation regimens for esophageal cancers has resulted in statistically significant survival benefits, the majority of patients treated with curative intent develop locoregional and/or distant relapse. Further improvements in disease control and survival will require the development of individualized therapy based on the knowledge of host and tumor genomics and potentially harnessing the host immune system. Although there are a number of gene targets that are amplified and proteins that are overexpressed in esophageal cancers, attempts to target several of these have not proven successful in unselected patients. Herein, we review our current state of knowledge regarding the molecular pathways implicated in esophageal carcinoma, and the available agents for targeting these pathways that may rationally be combined with standard chemoradiation, with the hope that this commentary will guide future efforts of novel combinations of therapy.
- Published
- 2020
20. Accurate, Precision Radiation Medicine: A Meta-Strategy for Impacting Cancer Care, Global Health, and Nuclear Policy and Mitigating Radiation Injury From Necessary Medical Use, Space Exploration, and Potential Terrorism
- Author
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David A. Pistenmma, Mansoor M. Ahmed, Jeffrey C. Buchsbaum, Jim A. Deye, Bhadrasain Vikram, Manjit Dosanjh, Eric J. Bernhard, Jacques Bernier, Jacek Capala, Ceferino Obcemea, Pataje G. S. Prasanna, and C. Norman Coleman
- Subjects
Cancer Research ,medicine.medical_specialty ,International Cooperation ,Decision Making ,Global Health ,Space exploration ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Radiation oncology ,medicine ,Global health ,Humans ,Organizational Objectives ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Precision Medicine ,Radiation Injuries ,Nuclear energy policy ,Radiation injury ,Societies, Medical ,Radiation ,business.industry ,Health Plan Implementation ,Cancer ,Radiation Exposure ,Space Flight ,Precision medicine ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Terrorism ,Radiation Oncology ,Interdisciplinary Communication ,business - Published
- 2018
21. National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury
- Author
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Stephanie A. Terezakis, Kenneth Wong, Kenneth J. Cohen, Mike Makrigiorgos, Vinai Gondi, David R. Grosshans, Jeff M. Michalski, Arthur K. Liu, Dragan Mirkovic, Tina Young Poussaint, Torunn I. Yock, Kry Stephen, Hanne M. Kooy, John A. Kalapurakal, Stella Flampouri, Kavita Mishra, Stephanie M. Perkins, Daphne A. Haas-Kogan, Harald Paganetti, Daniel J. Indelicato, Maryam Fouladi, Radhe Mohan, Thomas J. Fitzgerald, Shannon M. MacDonald, Anita Mahajan, Natia Esiashvili, Bhadrasain Vikram, Larry E. Kun, and Jeff Buchsbaum
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Infratentorial Neoplasms ,Cancer Care Facilities ,Article ,030218 nuclear medicine & medical imaging ,Necrosis ,03 medical and health sciences ,0302 clinical medicine ,Proton radiation ,Proton Therapy ,Humans ,Medicine ,Dosimetry ,Linear Energy Transfer ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Child ,Radiation Injuries ,Radiation treatment planning ,Proton therapy ,Photons ,Radiation ,Modalities ,business.industry ,Uncertainty ,Cancer ,medicine.disease ,Texas ,National Cancer Institute (U.S.) ,United States ,Radiation therapy ,Massachusetts ,Oncology ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Florida ,Radiotherapy, Intensity-Modulated ,Brainstem ,business ,Relative Biological Effectiveness ,Brain Stem - Abstract
Purpose Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury. Methods and Materials Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016. Results The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning. Conclusions Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.
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- 2018
22. Overview of the First NRG Oncology–National Cancer Institute Workshop on Dosimetry of Systemic Radiopharmaceutical Therapy
- Author
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Roncali, Emilie, primary, Capala, Jacek, additional, Benedict, Stanley H., additional, Akabani, Gamal, additional, Bednarz, Bryan, additional, Bhadrasain, Vikram, additional, Bolch, Wesley E., additional, Buchsbaum, Jeffrey C., additional, Coleman, Norman C., additional, Dewaraja, Yuni K., additional, Frey, Eric, additional, Ghaly, Michael, additional, Grudzinski, Joseph, additional, Hobbs, Robert F., additional, Howell, Roger W., additional, Humm, John L., additional, Kunos, Charles A., additional, Larson, Steve, additional, Lin, Frank I., additional, Madsen, Mark, additional, Mirzadeh, Saed, additional, Morse, David, additional, Pryma, Daniel, additional, Sgouros, George, additional, St. James, Sara, additional, Wahl, Richard L., additional, Xiao, Ying, additional, Zanzonico, Pat, additional, and Zukotynski, Katherine, additional
- Published
- 2020
- Full Text
- View/download PDF
23. National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer
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A. Bapsi Chakravarthy, Thomas J. George, Aaron J Franke, Timothy J. Kinsella, Theodore S. Hong, Terence M. Williams, C. Norman Coleman, James J. Lee, David Raben, Samuel A. Jacobs, Prajnan Das, Jerome C. Landry, Bassel F. El-Rayes, Christina Wu, Mansoor M. Ahmed, Arvind Dasari, Arta M. Monjazeb, Bhadrasain Vikram, and Osama E. Rahma
- Subjects
Oncology ,Radiation-Sensitizing Agents ,Cancer Research ,abscopal effect ,Colorectal cancer ,medicine.medical_treatment ,Herpesvirus 1, Human ,Disease ,radiation therapy ,B7-H1 Antigen ,chemoradiotherapy ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Molecular Targeted Therapy ,030212 general & internal medicine ,targeted therapeutics ,Protein Kinase C ,Cancer ,Abscopal effect ,Primary tumor ,Colo-Rectal Cancer ,Immunological ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Immunotherapy ,immunotherapy ,Patient Safety ,Mitogen-Activated Protein Kinases ,Colorectal Neoplasms ,Human ,Biotechnology ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Antineoplastic Agents ,colorectal cancer ,radiation biology ,Article ,03 medical and health sciences ,Clinical Research ,Internal medicine ,medicine ,Humans ,precision radiation medicine ,HSP90 Heat-Shock Proteins ,Oncology & Carcinogenesis ,rectal cancer ,Biological Products ,Herpesvirus 1 ,business.industry ,Pyrimidine Nucleosides ,medicine.disease ,United States ,National Cancer Institute (U.S.) ,Clinical trial ,Radiation therapy ,Good Health and Well Being ,radiosensitization ,Digestive Diseases ,business ,Chemoradiotherapy - Abstract
BACKGROUND: Colorectal cancer (CRC) represents a major public health problem as the second leading cause of cancer-related mortality in the United States. Of an estimated 140,000 newly diagnosed CRC cases in 2018, roughly one-third of these patients will have a primary tumor located in the distal large bowel or rectum. The current standard of care approach includes curative-intent surgery, often following preoperative (neoadjuvant) radiotherapy (RT) to increase rates of tumor downstaging, clinical and pathologic response, as well as improving surgical resection quality. However, despite advancements in surgical techniques, as well as sharpened precision of dosimetry offered by contemporary RT delivery platforms, the oncology community continues to face challenges related to disease relapse. METHODS: Ongoing investigations are aimed at testing novel radiosensitizing agents and treatments that might exploit the systemic antitumor effects of RT utilizing immunotherapies. If successful, these treatments may usher in a new curative paradigm for rectal cancers such that surgical interventions may be avoided. Importantly, this disease offers an opportunity to correlate matched paired biopsies, radiographic response and molecular mechanisms of treatment sensitivity and resistance with clinical outcomes. RESULTS: Herein, the authors highlight the available evidence from preclinical models and early-phase studies, with an emphasis on promising developmental therapeutics undergoing prospective validation in larger-scale clinical trials. CONCLUSIONS: This review by the NCI’s Radiation Research Program Colorectal Cancer Working Group provides an updated comprehensive examination of the continuously evolving State of the Science regarding radiosensitizer drug development in the curative treatment of CRC.
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- 2019
24. Advancing Targeted Radionuclide Therapy Through the National Cancer Institute’s Small Business Innovation Research Pathway
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Kaveh Zakeri, Greg Evans, Bhadrasain Vikram, Jeffrey C. Buchsbaum, Jacek Capala, Pataje G. S. Prasanna, and Deepa Narayanan
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Research program ,Targeted radionuclide therapy ,Request for proposal ,03 medical and health sciences ,0302 clinical medicine ,Inventions ,Neoplasms ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Molecular Targeted Therapy ,Small Business ,Small Business Innovation Research ,business.industry ,Cancer ,Small business ,medicine.disease ,Theranostics ,National Cancer Institute (U.S.) ,United States ,Engineering management ,Research Design ,030220 oncology & carcinogenesis ,Radionuclide therapy ,Technology transfer ,business - Abstract
The Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs of the National Cancer Institute (NCI) are congressionally mandated set-aside programs that provide research funding to for-profit small businesses for the development of innovative technologies and treatments that serve the public good. These two programs have an annual budget of $159 million (in 2017) and serve as the NCI's main engine of innovation for developing and commercializing cancer technologies. In collaboration with the NCI's Radiation Research Program, the NCI SBIR Development Center published in 2015-2017 three separate requests for proposals from small businesses for the development of systemic targeted radionuclide therapy (TRT) technologies to treat cancer. TRT combines a cytotoxic radioactive isotope with a molecularly targeted agent to produce an anticancer therapy capable of treating local or systemic disease. This article summarizes the NCI SBIR funding solicitations for the development of TRTs and the research proposals funded through them.
- Published
- 2019
25. Overview of the American Society for Radiation Oncology–National Institutes of Health–American Association of Physicists in Medicine Workshop 2015: Exploring Opportunities for Radiation Oncology in the Era of Big Data
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Jeff A. Sloan, Stanley H Benedict, Bhadrasain Vikram, Amy P. Abernethy, Anna Theriault, Karen E. Hoffman, B.S. Chera, Fred W. Prior, Eric C. Ford, Robert S. Miller, Kevin L. Moore, Brian D. Kavanagh, Anthony L. Asher, Ronald C. Chen, Jacek Capala, Jason A. Efstathiou, Vojtech Huser, Barry S. Rosenstein, Lawrence B. Marks, Deepak Khuntia, Peter Gabriel, Benedick A. Fraass, Charles S. Mayo, Mary K. Martel, Todd McNutt, Jennifer Couch, J Deye, Erik Roelofs, Radiotherapie, RS: GROW - School for Oncology and Reproduction, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
- Subjects
Cancer Research ,government.form_of_government ,Automatic identification and data capture ,Big data ,Clinical decision support system ,Health informatics ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Data Mining ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Registries ,Societies, Medical ,Radiation ,Data collection ,business.industry ,Genomics ,Data science ,United States ,Consensus Development Conferences, NIH as Topic ,Workflow ,National Institutes of Health (U.S.) ,Oncology ,Analytics ,030220 oncology & carcinogenesis ,Radiation Oncology ,government ,business ,Health Physics ,Incident report - Abstract
Big data research refers to the collection and analysis of large sets of data elements and interrelationships that are difficult to process with traditional methods. It can be considered a subspecialty of the medical informatics domain under data science and analytics. This approach has been used in many areas of medicine to address topics such as clinical care and quality assessment (1–3). The need for informatics research in radiation oncology emerged as an important initiative during the 2013 National Institutes of Health (NIH)–National Cancer Institute (NCI), American Society for Radiation Oncology (ASTRO), and American Association of Physicists in Medicine (AAPM) workshop on the topic “Technology for Innovation in Radiation Oncology” (4). Our existing clinical practice generates discrete, quantitative, and structured patient-specific data (eg, images, doses, and volumes) that position us well to exploit and participate in big data initiatives. The well-established electronic infrastructure within radiation oncology should facilitate the retrieval and aggregation of much of the needed data. With additional efforts to integrate structured data collection of patient outcomes and assessments into the clinical workflow, the field of radiation oncology has a tremendous opportunity to generate large, comprehensive patient-specific data sets (5). However, there are major challenges to realizing this goal. For example, existing data are presently housed across different platforms at multiple institutions and are often not stored in a standardized manner or with common terminologies to enable pooling of data. In addition, many important data elements are not routinely discretely captured in clinical practice. There are cultural, structural, and logistical challenges (eg, computer compatibility and workflow demands) that will make the dream of big data research difficult. The big data research workshop provided a forum for leaders in cancer registries, incident report quality-assurance systems, radiogenomics, ontology of oncology, and a wide range of ongoing big data and cloud computing development projects to interact with peers in radiation oncology to develop strategies to harness data for research, quality assessment, and clinical care. The workshop provided a platform to discuss items such as data capture, data infrastructure, and protection of patient confidentiality and to improve awareness of the wide-ranging opportunities in radiation oncology, as well as to enhance the potential for research and collaboration opportunities with NIH on big data initiatives. The goals of the workshop were as follows: To discuss current and future sources of big data for use in radiation oncology research, To identify ways to improve our current data collection methods by adopting new strategies used in fields outside of radiation oncology, and To consider what new knowledge and solutions big data research can provide for clinical decision support for personalized medicine.
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- 2016
26. Education and Training Needs in the Radiation Sciences: Problems and Potential Solutions
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Kathryn D. Held, Bhadrasain Vikram, Michael C. Joiner, James A. Deye, Joseph R. Dynlacht, and Elaine M. Zeman
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medicine.medical_specialty ,Medical education ,Radiation ,Las vegas ,business.industry ,Health physics ,Radiation oncology ,Biophysics ,Medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Training needs ,business - Abstract
This article provides a summary of presentations focused on critical education and training issues in radiation oncology, radiobiology and medical physics from a workshop conducted as part of the 60th Annual Meeting of the Radiation Research Society held in Las Vegas, NV (September 21-24, 2014). Also included in this synopsis are pertinent comments and concerns raised by audience members, as well as recommendations for addressing ongoing and future challenges.
- Published
- 2015
27. Development of Novel Radiosensitizers through the National Cancer Institute's Small Business Innovation Research Program
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Jeffrey C. Buchsbaum, Pataje G. S. Prasanna, Kaveh Zakeri, Deepa Narayanan, and Bhadrasain Vikram
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Radiation-Sensitizing Agents ,medicine.medical_specialty ,Standard of care ,Biophysics ,Request for proposal ,Improved survival ,Article ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Drug Discovery ,Overall survival ,medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Small Business ,Small Business Innovation Research ,Radiation ,business.industry ,Research ,Cancer ,medicine.disease ,National Cancer Institute (U.S.) ,United States ,Clinical trial ,030220 oncology & carcinogenesis ,business - Abstract
While radiosensitizing chemotherapy has improved survival for several types of cancer, current chemoradiation regimens remain ineffective for many patients and have substantial toxicities. Given the strong need for the development of novel radiosensitizers to further improve patient outcomes, the Radiation Research Program (RRP) and the Small Business Innovation Research (SBIR) in the National Cancer Institute (NCI) issued a Request for Proposals (RFP) through the NCI SBIR Development Center's contracts pathway. We sought to determine the research outcomes for the NCI SBIR Development Center's funded proposals for the development of radiosensitizers. We identified SBIR-funded contracts and grants for the development of radiosensitizers from 2009 to 2018 using the National Institutes of Health (NIH) Reporter database. Research outcomes of the NCI SBIR Development Center-funded proposals were determined using a comprehensive internet search. We searched PubMed, clinicaltrials.gov, company websites and google.com for research articles, abstracts and posters, clinical trials, press releases and other news, related to progress in the development of funded radiosensitizers. To protect the intellectual property of the investigators and small businesses, all information obtained and reported is publicly available. The SBIR Program has funded four contracts and 11 grants for the development of novel radiosensitizers. Two companies have received phase IIb bridge awards. Overall, 50% of companies (6/12) have successfully advanced their investigational drugs into prospective clinical trials in cancer patients, and all but one company are investigating their drug in combination with radiation therapy as described in the NCI SBIR Development Center proposal. To date, only one company has initiated a randomized trial of standard of care with or without their radiosensitizer. In conclusion, the NCI SBIR Development Center has funded the development of novel radiosensitizers leading to clinical trials of novel drugs in combination with radiation therapy. Continued follow-up is needed to determine if any of these novel radiosensitizers produce improved tumor control and/or overall survival.
- Published
- 2020
28. Radiation Biomarkers: Can Small Businesses Drive Accurate Radiation Precision Medicine?
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Deepa Narayanan, Bhadrasain Vikram, C. Norman Coleman, Pataje G. S. Prasanna, Kehui Zhang, and Amir Rahbar
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Biophysics ,MEDLINE ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Radiation sensitivity ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Precision Medicine ,Radiation ,Radiotherapy ,business.industry ,Commerce ,Cancer ,Precision medicine ,medicine.disease ,Clinical trial ,Radiation therapy ,Treatment interruption ,030220 oncology & carcinogenesis ,business ,Biomarkers - Abstract
Radiation therapy is an essential component of cancer treatment. Currently, tumor control and normal tissue complication probabilities derived from a general patient population guide radiation treatment. Its outcome could be improved if radiation biomarkers could be incorporated into approaches to treatment. A substantial number of cancer patients suffer from side effects of radiation therapy. These side effects can result in treatment interruption. Such unplanned treatment interruptions not only jeopardize anticancer treatment efficacy but also result in poor post-treatment quality-of-life. To develop and translate radiation biomarkers for clinical use, NCI's Radiation Research Program, in collaboration with the Small Business Innovation Research Development Center, funded four small businesses through the request for proposals after peer review during 2015-2019. Here, we summarize publicly available information on intellectual property rights, the status of development, ongoing clinical trials, success in obtaining financing and regulatory approval. An analysis of publicly available information indicates all four companies have completed phase I of SBIR funding and advanced to further development, validation and clinical trials with phase II SBIR funding. These biomarkers are: 1. A panel of genomic biomarkers of radiation response to predict toxicity and radioimmune response (MiraDx Inc., Los Angeles, CA); 2. A multiplex assay for single nucleotide polymorphism (SNP) biomarkers of radiation sensitivity to identify a subset of prostate cancer patients for which radiotherapy is contraindicated (L2 Diagnostics, New Haven, CT); 3. A cell-free DNA assay in blood to measure tissue damage shortly after radiation exposure (DiaCarta Inc., Richmond, CA); and 4. A metabolomic/lipidomic assay to predict late effects that adversely affect quality-of-life among patients treated with radiation for prostate cancer (Shuttle Pharmaceuticals, Rockville, MD). This work also provides a bird's eye view of the process of developing radiation biomarkers for use in radiation oncology clinics, some of the challenges and future directions.
- Published
- 2020
29. Decreasing the Toxicity of Radiation Therapy: Radioprotectors and Radiomitigators Being Developed by the National Cancer Institute Through Small Business Innovation Research Contracts
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C. Norman Coleman, Pataje G. S. Prasanna, Greg Evans, Bhadrasain Vikram, Kaveh Zakeri, and Deepa Narayanan
- Subjects
Cancer Research ,Research program ,medicine.medical_specialty ,Financing, Government ,medicine.medical_treatment ,Request for proposal ,Contracts ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Radiation Protection ,Inventions ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Small Business ,Small Business Innovation Research ,Technology, Radiologic ,Radiation ,INVESTIGATIONAL AGENTS ,business.industry ,National Cancer Institute (U.S.) ,United States ,Radiation therapy ,Clinical trial ,Clinical Practice ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
Purpose The use of radioprotectors and radiomitigators could improve the therapeutic index of radiation therapy. With the intention of accelerating translation of radiation-effect modulators (radioprotectors and mitigators), the Radiation Research Program and SBIR (Small Business Innovation Research) Development Center within the National Cancer Institute issued 4 Requests for Proposals (RFPs) from 2010 to 2013. Twelve SBIR contract awards in total were made in response to the 4 RFPs from September 2011 through September 2014. Here, we provide an update on the status of SBIR contract projects for the development of radiation-effect modulators. Methods and Materials To assess the status of research and development efforts under the 4 RFPs on radiation-effect modulators, we searched PubMed for research articles, google.com for published abstracts, clinicaltrials.gov for ongoing or completed clinical trials, and company websites for press releases and other news. All information obtained and reported here is publicly available and thus protects the intellectual property of the investigators and companies. Results Of the 12 SBIR projects funded, 5 (42%) transitioned successfully from phase 1 to phase 2 SBIR funding, and among the Fast-Track contracts, this rate was 100% (3 of 3). The Internet search identified 3 abstracts and 6 publications related to the aims of the SBIR contracts. One-third of the companies (4 of 12) have successfully launched a total of 8 clinical trials to demonstrate the safety and efficacy of their investigational agents. Two drugs are in clinical trials for their indication as a radioprotector, and 2 drugs are under evaluation for their anticancer properties (an immunomodulator and a small molecule inhibitor). Conclusions The National Cancer Institute's SBIR has provided pivotal funding to small businesses for the development of radioprotectors and radiomitigators, which resulted in multiple early-phase clinical trials. Longer follow-up is needed to determine the full impact of these novel therapeutics that enter clinical practice.
- Published
- 2018
30. Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation
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Bhadrasain Vikram, J. Jack Lee, Erich M. Sturgis, G. Brandon Gunn, Nancy Y. Lee, Adam S. Garden, David I. Rosenthal, Stephen Y. Lai, Merrill S. Kies, Pierre Blanchard, Paul M. Busse, C. David Fuller, Alexander Lin, Katherine A. Hutcheson, Mitchell Machtay, Robert L. Foote, and Steven J. Frank
- Subjects
Male ,Organs at Risk ,Cancer Research ,medicine.medical_specialty ,Endpoint Determination ,medicine.medical_treatment ,Disease-Free Survival ,Article ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Clinical Trials, Phase II as Topic ,Randomized controlled trial ,Quality of life ,law ,Clinical endpoint ,Proton Therapy ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,Proton therapy ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Photons ,business.industry ,Head and neck cancer ,Cancer ,Radiotherapy Dosage ,medicine.disease ,Texas ,Clinical trial ,Radiation therapy ,Oropharyngeal Neoplasms ,Oncology ,Clinical Trials, Phase III as Topic ,Research Design ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,Radiology ,Radiotherapy, Intensity-Modulated ,business - Abstract
Intensity-modulated proton therapy minimizes the incidental irradiation of normal tissues in patients with head and neck cancer relative to intensity-modulated photon (x-ray) therapy and has been associated with lesser treatment-related toxicity and improved quality of life. A phase II/III randomized trial sponsored by the US National Cancer Institute is currently underway to compare deintensification treatment strategies with intensity-modulated proton therapy vs intensity-modulated photon (x-ray) therapy for patients with advanced-stage oropharyngeal tumors. After significant input from numerous stakeholders, the phase III portion of the randomized trial was redesigned as a noninferiority trial with progression-free survival as the primary endpoint. The process by which that redesign took place is described here.
- Published
- 2018
31. Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches-Meeting Viewpoint
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Silvia C. Formenti, Radhe Mohan, Molykutty J. Aryankalayil, Pataje G. S. Prasanna, Stephen M. Seltzer, Søren M. Bentzen, Beverly A. Teicher, Jeffrey C. Buchsbaum, Joel E. Tepper, David Raben, Gary D. Kao, Kevin M. Prise, David G. Kirsch, Bhadrasain Vikram, Fei-Fei Liu, Deborah Citrin, Daphne A. Haas-Kogan, Mansoor M. Ahmed, James B. Mitchell, Dee Dee K. Smart, Jacek Capala, Dudley T. Goodhead, Marc S. Mendonca, Ceferino Obcemea, Quynh-Thu Le, C. Norman Coleman, and Iris Eke
- Subjects
Cancer Research ,medicine.medical_specialty ,Particle therapy ,business.industry ,Quantitative Biology::Tissues and Organs ,medicine.medical_treatment ,Physics::Medical Physics ,030218 nuclear medicine & medical imaging ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,SDG 3 - Good Health and Well-being ,030220 oncology & carcinogenesis ,medicine ,Journal Article ,Medical physics ,business - Abstract
The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons and heavier ions such as carbon. The unit of dose deposited is the gray (Gy); however, particle therapies produce different patterns of ionizations, and
- Published
- 2018
32. Toward A variable RBE for proton beam therapy
- Author
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Stephen J. McMahon, Claudia Wiese, Henning Willers, Cläre von Neubeck, David R. Grosshans, Bhadrasain Vikram, and Antiño R. Allen
- Subjects
0301 basic medicine ,DNA Repair ,DNA repair ,Normal tissue ,Medizin ,Bioinformatics ,Relative biological effectiveness ,03 medical and health sciences ,Tumor Biomarkers ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,In vivo ,Neoplasms ,Proton Therapy ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,business.industry ,Hematology ,030104 developmental biology ,Oncology ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Normal tissue toxicity ,Carbon ions ,Protons ,business ,Relative Biological Effectiveness - Abstract
In the clinic, proton beam therapy (PBT) is based on the use of a generic relative biological effectiveness (RBE) of 1.1 compared to photons in human cancers and normal tissues. However, the experimental basis for this RBE lacks any significant number of representative tumor models and clinically relevant endpoints for dose-limiting organs at risk. It is now increasingly appreciated that much of the variations of treatment responses in cancers are due to inter-tumoral genomic heterogeneity. Indeed, recently it has been shown that defects in certain DNA repair pathways, which are found in subsets of many cancers, are associated with a RBE increase in vitro. However, there currently exist little in vivo or clinical data that confirm the existence of similarly increased RBE values in human cancers. Furthermore, evidence for variable RBE values for normal tissue toxicity has been sparse and conflicting to date. If we could predict variable RBE values in patients, we would be able to optimally use and personalize PBT. For example, predictive tumor biomarkers may facilitate selection of patients with proton-sensitive cancers previously ineligible for PBT. Dose de-escalation may be possible to reduce normal tissue toxicity, especially in pediatric patients. Knowledge of increased tumor RBE may allow us to develop biologically optimized therapies to enhance local control while RBE biomarkers for normal tissues could lead to a better understanding and prevention of unusual PBT-associated toxicity. Here, we will review experimental data on the repair of proton damage to DNA that impact both RBE values and biophysical modeling to predict RBE variations. Experimental approaches for studying proton sensitivity in vitro and in vivo will be reviewed as well and recent clinical findings discussed. Ultimately, therapeutically exploiting the understudied biological advantages of protons and developing approaches to limit treatment toxicity should fundamentally impact the clinical use of PBT.
- Published
- 2018
33. Research in imaging/biomarkers for precision medicine in lung cancer: National Cancer Institute funding opportunities
- Author
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Bhadrasain Vikram
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Alternative medicine ,Cancer ,medicine.disease ,Precision medicine ,Radiation therapy ,Editorial ,Oncology ,medicine ,Medical physics ,Lung cancer ,business - Abstract
Radiation therapy (RT) is employed in all stages of lung cancer. In this article, I will highlight some areas where improvement is needed. We at the National Cancer Institute (NCI) welcome proposals addressing those needs.
- Published
- 2017
34. Current Status of Radiation Oncology Research funded through the National Cancer Institute’s Small Business Innovation Research Program
- Author
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Greg Evans, Bhadrasain Vikram, C.N. Coleman, Jacek Capala, Jeffrey C. Buchsbaum, M. Weingarten, Deepa Narayanan, Pataje G. S. Prasanna, and Kaveh Zakeri
- Subjects
Cancer Research ,Medical education ,Radiation ,Oncology ,business.industry ,Radiation oncology ,Medicine ,Cancer ,Radiology, Nuclear Medicine and imaging ,Current (fluid) ,business ,medicine.disease ,Small Business Innovation Research - Published
- 2018
35. Overview of the First NRG-NCI Workshop on Dosimetry of Systemic Radiopharmaceutical Therapy (RPT).
- Author
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Roncali, Emilie, Capala, Jacek, Benedict, Stanley H., Akabani, Gamal, Bednarz, Bryan, Bhadrasain, Vikram, Bolch, Wesley E., Buchsbaum, Jeffrey C., Clarke, Bonnie, Coleman, Norman C., Dewaraja, Yuni K., Frey, Eric, Ghaly, Michael, Grudzinski, Joseph, Hobbs, Robert F., Howell, Roger W., Humm, John L., Kunos, Charles A., Larson, Steve, and Lin, Frank I.
- Published
- 2020
- Full Text
- View/download PDF
36. Radiation-induced brain damage, impact of Michael Robbins’ work and the need for predictive biomarkers
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Helen B. Stone, C. Norman Coleman, Bhadrasain Vikram, Pataje G. S. Prasanna, Mansoor M. Ahmed, and Minesh P. Mehta
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Context (language use) ,Radiation induced ,Brain damage ,Radiation Dosage ,Radiosurgery ,Quality of life ,Internal medicine ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,Predictive biomarker ,Chemotherapy ,Radiological and Ultrasound Technology ,Brain Neoplasms ,business.industry ,Brain ,Cognition ,Surgery ,Radiation therapy ,Brain Injuries ,Radiation Oncology ,medicine.symptom ,business ,Biomarkers - Abstract
To review the literature on radiation-induced normal tissue injury in the context of treatment of primary and metastatic brain tumors with a focus on Michael Robbins' work on mechanisms of injury and approaches to mitigation, and also to identify other potential opportunities to improve treatment outcome and quality of life (QOL).Brain tumors remain a significant challenge for patients, their families, the physicians treating them, and researchers seeking more effective treatments. Current treatment of brain tumors involves combinations of radiotherapy with surgery, chemotherapy, and molecularly targeted agents. As patient survival improves with advances in treatment there is an increasing concern for the cognitive deficits that may become apparent months or years after treatment some of which are related to radiation-induced brain damage. One area of Michael Robbins' research was unraveling the mechanisms of radiation-induced cognitive deficits, which formed the basis for the development of some mitigators of radiation injury. Extrapolating from this, new opportunities to identify and develop putative predictive biomarkers of radiation-induced brain damage can be explored.Predictive biomarkers of radiation-induced brain injury may enable stratifying patients for customization of treatment and thus aid in improving the QOL and possibly prolonging survival. Here we discuss the challenges involved in leveraging recent advances in radiation-specific biomarker research and translating them to radiotherapy, which for the foreseeable future is likely to remain a cornerstone of the treatment of brain tumors.
- Published
- 2014
37. Perspectives on potential research benefits from big data efforts in Radiation Oncology
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Bhadrasain Vikram
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Big Data ,Male ,business.industry ,Big data ,MEDLINE ,General Medicine ,Data science ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Radiation oncology ,Radiation Oncology ,Humans ,Medicine ,Female ,030212 general & internal medicine ,business - Published
- 2018
38. Reply to Z. Liao et al and R. Rengan et al
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Feng-Ming Kong and Bhadrasain Vikram
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03 medical and health sciences ,Cancer Research ,0302 clinical medicine ,Oncology ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,business ,Humanities ,030218 nuclear medicine & medical imaging - Published
- 2018
39. Lessons Learned from Radiation Oncology Clinical Trials
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Stephen S. Yoo, Fei-Fei Liu, Martin Brown, Eric J. Bernhard, Chandan Guha, C. Norman Coleman, Paul Okunieff, Helen B. Stone, Bhadrasain Vikram, and John M. Buatti
- Subjects
Clinical Trials as Topic ,Cancer Research ,medicine.medical_specialty ,Quality Assurance, Health Care ,business.industry ,Clinical study design ,education ,Alternative medicine ,Combined Modality Therapy ,Preclinical data ,Article ,Clinical trial ,Patient benefit ,Oncology ,Neoplasms ,Radiation oncology ,Biomarkers, Tumor ,medicine ,Humans ,Medical physics ,Treatment Failure ,Cancer biology ,Null hypothesis ,business - Abstract
A workshop entitled “Lessons Learned from Radiation Oncology Trials” was held on December 7–8, 2011, in Bethesda, MD, to present and discuss some of the recently conducted radiation oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the preclinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions: (i) opportunities to learn from null-hypothesis trials through tissue and imaging studies; (ii) value of preclinical data supporting the design of combinatorial therapies; (iii) significance of validated biomarkers; (iv) necessity of quality assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies to address the central hypotheses; and (vi) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design and complexities of cancer biology. It is important to understand the reasons underlying such null results, however, to effectively merge the technologic innovations with the rapidly evolving biology for maximal patient benefit through the design of future clinical trials. Clin Cancer Res; 19(22); 6089–100. ©2013 AACR.
- Published
- 2013
40. Better cancer control for worldwide populations at the margins of healthcare: Direct big-issues talk and due diligence
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C. Norman Coleman, Richard R. Love, Bhadrasain Vikram, and Daniel G. Petereit
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Less-developed countries ,Economic growth ,Epidemiology ,Cancer signs and symptoms ,Healthcare disparities ,media_common.quotation_subject ,Developing country ,Social issues ,03 medical and health sciences ,Underserved Population ,0302 clinical medicine ,Health care ,Development economics ,Human rights ,Medicine ,030212 general & internal medicine ,Burden of illness ,10. No inequality ,Socioeconomic status ,Cancer ,media_common ,business.industry ,Health Policy ,1. No poverty ,Community medicine ,Due diligence ,3. Good health ,Oncology ,Access to health care ,030220 oncology & carcinogenesis ,Sociology of medicine ,business - Abstract
While there is increasing attention to cancer among underserved populations globally, recent publications have suggested that discussions often ignore the broad but critical issues and lack due diligence. This communication considers these subjects. We all seek honest governments, recognition of women's and other human rights, protection of minorities, the fostering of education for all, and the rendering of fair justice. Absence of these overwhelms efforts in cancer care. Massive rural-urban migration and the majority of cancer burdens globally occurring among the huge populations of poor Asians are also dominating realities. In-depth understanding of how people actually live must ground our efforts. Weak governments, weak health systems, and widespread corruption adversely impact work to improve cancer outcomes. Some implications of these painful circumstances are first that cancer-specific, top-down approaches may be less suitable and less effective than locally defined efforts sensitive to particular broad issues. Second, that widespread drug availability may be less an economic issue than a social systems issue. Third, patient education about cancer signs and symptoms may be less useful than direct efforts targeting broad human rights issues to give patients real choices to seek care. We suggest that addressing cancer control for underserved populations needs to be more of an exercise in addressing the major societal issues, living noble values, investigating to see things as they really are, and acting from a model of intervention suitable to the broad complex challenges.
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- 2013
- Full Text
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41. NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers
- Author
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Walter J. Curran, James J. Dignam, Bhadrasain Vikram, Arnab Chakravarti, Paul Okunieff, Boris Freidlin, Naoko Takebe, Søren M. Bentzen, C. Norman Coleman, Yaacov Richard Lawrence, Mitchell Machtay, and Adam P. Dicker
- Subjects
Radiation-Sensitizing Agents ,Cancer Research ,medicine.medical_specialty ,Time Factors ,DNA Repair ,medicine.medical_treatment ,Phases of clinical research ,Antineoplastic Agents ,Translational research ,Pharmacology ,Drug Administration Schedule ,Translational Research, Biomedical ,Clinical Trials, Phase II as Topic ,Neoplasms ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Immunologic Factors ,Medical physics ,Molecular Targeted Therapy ,Response rate (survey) ,Clinical Trials as Topic ,Clinical Trials, Phase I as Topic ,Radiotherapy ,Cytotoxins ,business.industry ,Surrogate endpoint ,Dose fractionation ,Cytostatic Agents ,Cell Hypoxia ,National Cancer Institute (U.S.) ,United States ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Radiation therapy ,Clinical trial ,Disease Models, Animal ,Oncology ,Drug development ,Research Design ,Drug Design ,Commentary ,Dose Fractionation, Radiation ,business ,DNA Damage ,Signal Transduction - Abstract
The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry's diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials-acute toxicity and maximum-tolerated dose-are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II "screening" trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation.
- Published
- 2012
42. Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration
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Charles A. Kunos, Mansoor M. Ahmed, Eric J. Bernhard, C. Norman Coleman, Bhadrasain Vikram, Naoko Takebe, and James A. Zwiebel
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0301 basic medicine ,Research design ,Cancer Research ,medicine.medical_specialty ,Radiation-Sensitizing Agents ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,Clinical Trials, Phase II as Topic ,Neoplasms ,Radiation oncology ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Therapy Evaluation ,Clinical Trials, Phase I as Topic ,business.industry ,Cancer ,Radiobiology ,medicine.disease ,Preclinical data ,National Cancer Institute (U.S.) ,United States ,Clinical trial ,030104 developmental biology ,Oncology ,Research Design ,030220 oncology & carcinogenesis ,Early phase ,business - Abstract
A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next-step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation-agent development initiatives.
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- 2016
43. Establishing global health cancer care partnerships across common ground: bridging nuclear security, equitable access, education, outreach, and mentorship
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Danielle Rodin, Surbhi Grover, Nelson J. Chao, David A. Pistenmaa, David A. Jaffray, Nina Wendling, Lawrence Roth, Majid M. Mohiuddin, C. Norman Coleman, Mary Gospodarowicz, Bhadrasain Vikram, Daniel G. Petereit, Silvia C. Formenti, and Tim R. Williams
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Outreach ,Bridging (networking) ,Mentorship ,business.industry ,lcsh:Public aspects of medicine ,Global health ,Common ground ,Medicine ,lcsh:RA1-1270 ,General Medicine ,Public relations ,business - Published
- 2016
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44. The International Cancer Expert Corps (ICEC): Implementing a global force to address the catastrophic rise in cancer in the developing world
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Tim R. Williams, N. Chao, Daniel G. Petereit, C.N. Coleman, Danielle Rodin, Silvia C. Formenti, David A. Pistenmaa, Mohammed Mohiuddin, Surbhi Grover, and Bhadrasain Vikram
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Economic growth ,Oncology ,Radiology Nuclear Medicine and imaging ,Political science ,medicine ,Cancer ,Developing country ,Radiology, Nuclear Medicine and imaging ,Hematology ,medicine.disease - Published
- 2016
- Full Text
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45. Is There A Role for Radiotherapy In Experimental Therapeutic Drug Development?
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Charles A. Kunos and Bhadrasain Vikram
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Radiation therapy ,Experimental chemotherapy ,medicine.medical_specialty ,Drug development ,business.industry ,medicine.medical_treatment ,medicine ,Medical physics ,Bioinformatics ,business ,Precision medicine - Published
- 2016
46. Radiotherapy for Hepatocellular Carcinoma: New Indications and Directions for Future Study
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Nitin Ohri, Mansoor M. Ahmed, Sunil Krishnan, Bhadrasain Vikram, Laura A. Dawson, Jason Chia-Hsien Cheng, Jinsil Seong, M. Kinkhabwala, Shiv Kumar Sarin, Chandan Guha, and C. Norman Coleman
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation-Sensitizing Agents ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Disease ,Liver transplantation ,Radiosurgery ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Carcinoma ,medicine ,Biomarkers, Tumor ,Humans ,neoplasms ,Cancer Death Rate ,business.industry ,Liver Neoplasms ,Cancer ,medicine.disease ,Combined Modality Therapy ,digestive system diseases ,Liver Transplantation ,Radiation therapy ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Immunotherapy ,business - Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide; its incidence is increasing in the United States. Depending on disease extent and underlying liver status, patients may be treated with local, locoregional, and/or systemic therapy. Recent data indicates that radiotherapy (RT) can play a meaningful role in the management of HCC. Here, we review published experiences using RT for HCC, including the use of radiosensitizers and stereotactic RT. We discuss methods for performing preclinical studies of RT for HCC and biomarkers of response. As a part of the HCC Working Group, an informal committee of the National Cancer Institute's Radiation Research Program, we suggest how RT should be implemented in the management of HCC and identify future directions for the study of RT in HCC.
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- 2015
47. How Will Big Data Improve Clinical and Basic Research in Radiation Therapy?
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John Wong, Jason A. Efstathiou, Fred W. Prior, Jacek Capala, Jeff Hammerbacher, Ying Xiao, Feng-Ming Spring Kong, Bhadrasain Vikram, Barry S. Rosenstein, Sarah L. Kerns, and Harry Ostrer
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Cancer Research ,medicine.medical_specialty ,Biomedical Research ,Databases, Factual ,medicine.medical_treatment ,education ,Health informatics ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Basic research ,Neoplasms ,Radiation oncology ,Medicine ,Data Mining ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,General hospital ,Precision Medicine ,health care economics and organizations ,Radiation ,Radiotherapy ,business.industry ,Data Collection ,Medical school ,Precision medicine ,humanities ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Radiation Oncology ,business - Abstract
*Departments of Radiation Oncology, Genetics and Genomic Sciences, Dermatology and Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; yDepartment of Radiation Oncology, New York University School of Medicine, New York, New York; zClinical Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; xDepartment of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; kDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; {Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York; Department of Radiation Oncology, GRU Cancer Center and Medical College of Georgia, Georgia Regents University, Augusta, Georgia; **Departments of Pathology and Pediatrics, Albert Einstein College of Medicine, Bronx, New York; yyDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, Arkansas; zzDepartment of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and xxDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
- Published
- 2015
48. Decreasing the Adverse Effects of Cancer Therapy: An NCI Workshop on the Preclinical Development of Radiation Injury Mitigators/Protectors
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Sunil Krishnan, Bhadrasain Vikram, Julie L. Ryan, C. Norman Coleman, Stephen S. Yoo, and Benjamin Movsas
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Oncology ,medicine.medical_specialty ,Maximum Tolerated Dose ,Chemistry, Pharmaceutical ,Drug Evaluation, Preclinical ,Biophysics ,Cancer therapy ,Radiation-Protective Agents ,Tumor cells ,Pharmacology ,Article ,Radiation Protection ,Neoplasms ,Internal medicine ,Animals ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,Adverse effect ,Radiation injury ,Clinical Trials as Topic ,Radiation ,business.industry ,National Cancer Institute (U.S.) ,United States ,Cancer treatment ,Clinical trial ,Maximum tolerated dose ,embryonic structures ,Normal tissue toxicity ,business - Abstract
The study of radiation mitigators/protectors for use in cancer treatment and management is complex as they must reduce normal tissue toxicity without reducing tumor cell kill. The known toxicology, pharmacokinetic, and mechanistic data for the proposed agent will direct investigators to the appropriate stage of preclinical development. Overall, we hope that this Workshop commentary facilitates the transition of radiation mitigators/protectors into clinical trials.
- Published
- 2011
49. The Medical Student Perspective on Global Health Care in Radiation Oncology: Opportunities, Barriers to Sustainability, and Future Directions
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C. Norman Coleman, Bhadrasain Vikram, Maithili Daphtary, and Jeffrey Burkeen
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Program evaluation ,Cancer Research ,medicine.medical_specialty ,Capacity Building ,Students, Medical ,Organizations, Nonprofit ,MEDLINE ,Developing country ,Global Health ,Neoplasms ,Radiation oncology ,medicine ,Global health ,Humans ,Radiology, Nuclear Medicine and imaging ,Program Development ,Developing Countries ,Radiation ,business.industry ,Perspective (graphical) ,Internship and Residency ,Capacity building ,Oncology ,Family medicine ,Sustainability ,Radiation Oncology ,Engineering ethics ,business ,Forecasting ,Program Evaluation - Published
- 2014
50. Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities: Current Challenges and New Approaches: Report of the Symposium Held at the 63rd Annual Meeting of the Radiation Research Society, 15–18 October 2017; Cancun, Mexico
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Yaacov Richard Lawrence, Ricky A. Sharma, C. Norman Coleman, Pataje G. S. Prasanna, Sunil J. Advani, Mansoor M. Ahmed, Bhadrasain Vikram, Richard A. Amos, and Kelly C. Falls
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0301 basic medicine ,medicine.medical_specialty ,Research program ,Radiation ,business.industry ,Biophysics ,Normal tissue ,Article ,Scientific evidence ,03 medical and health sciences ,Preclinical research ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Radiation oncology ,Medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Professional association ,business ,Repurposing - Abstract
The National Cancer Institute’s (NCI) Radiation Research Program (RRP) is endeavoring to increase the relevance of preclinical research to improve outcomes of radiation therapy for cancer patients. These efforts include conducting symposia, workshops and educational sessions at annual meetings of professional societies, including the American Association of Physicists in Medicine, American Society of Radiation Oncology, Radiation Research Society (RRS), Radiosurgery Society, Society of Nuclear Medicine and Molecular Imaging, Society for Immunotherapy of Cancer and the American Association of Immunology. A symposium entitled “Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities” was conducted by the NCI’s RRP during the 63rd Annual Meeting of the RRS on October 16, 2017 in Cancun, Mexico. In this symposium, discussions were held to address the challenges in developing radiation-drug combinations, optimal approaches with scientific evidence to replace standard-of-care, approaches to reduce normal tissue toxicities and enhance post-treatment quality-of-life and recent advances in antibody-drug conjugates. The symposium included two broad overview talks followed by two talks illustrating examples of radiation-drug combinations under development. The overview talks identified the essential preclinical infrastructure necessary to accelerate progress in the development of evidence and important challenges in the translation of drug combinations to the clinic from the laboratory. Also addressed, in the example talks (in light of the suggested guidelines and identified challenges), were the development and translation of novel antibody drug conjugates as well as repurposing of drugs to improve efficacy and reduce normal tissue toxicities. Participation among a cross section of clinicians, scientists and scholars-in-training alike who work in this focused area highlighted the importance of continued discussions to identify and address complex challenges in this emerging area in radiation oncology.
- Published
- 2018
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