Framework for Quality Assurance of Ultrahigh Dose Rate Clinical Trials Investigating FLASH Effects and Current Technology Gaps
Year: 2023
Type: article
Abstract: FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials.
Authors: Wei Zou, Rongxiao Zhang, Emil Schüler, Paige A. Taylor, Anthony E. Mascia, Eric S. Diffenderfer, Tianyu Zhao, Ahmet S. Ayan, Manju Sharma, Shu-Jung Yu, Weiguo Lu, Walter R. Bosch, Christina Tsien, Murat Surucu, Julianne M. Pollard-Larkin, Jan Schuemann, Eduardo G. Moros, Magdalena Bazalova-Carter, David J. Gladstone, Heng Li, Charles B. Simone, Kristoffer Petersson, Stephen F. Kry, Amit Maity, Billy W. Loo, Lei Dong, Peter G. Maxim, Ying Xiao, Jeffrey C. Buchsbaum
Institutions: University of Pennsylvania, Dartmouth College, The University of Texas MD Anderson Cancer Center, Cincinnati Children's Hospital Medical Center, Washington University in St. Louis, The Ohio State University, University of California, San Francisco, Stanford Medicine, Stanford University, The University of Texas Southwestern Medical Center, McGill University Health Centre, McGill University, Harvard University, Massachusetts General Hospital, Moffitt Cancer Center, University of Victoria, Johns Hopkins University, New York Proton Center, University of Oxford, CRUK/MRC Oxford Institute for Radiation Oncology, University of California, Irvine, National Institutes of Health, National Cancer Institute
Language: English
Subfield: Radiation
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
Funders: Damon Runyon Cancer Research Foundation, Cancer Prevention and Research Institute of Texas, Massachusetts General Hospital, Patient-Centered Outcomes Research Institute, University of Pennsylvania, Varian Medical Systems, American Association of Physicists in Medicine, Cancer Research UK, Canada Research Chairs, Brain Tumour Charity, National Institutes of Health, University of Texas MD Anderson Cancer Center, Medical Research Council, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering
Awards: G111615301, Mechanistic Insights into FLASH radiation for clinical use, G1374137222, G1425319748, G1454588947, G1468253849, G1490528589, G1500204946, G1759008327, G1901027039, Washington University/ Siteman Cancer Center Lead Academic Site, G2012992077, G2291751764, G2554729840, G293715275, G3853912554, G3979912349, G41353926, G4276892241, NRG Oncology Network Group Operations Center, Markers of Cardiotoxicity with Radiation Therapy in Breast Cancer, G4780930090, G5118354679, Recruitment of Rising Stars, G5520316217, G5522554483, G5922134162, G5981877173, G6180657462, G6736661663, G6869263340, G7069883025, G7185013638, G7269819414, Towards Carbon Beam Stereotactic Body Radiation Therapy (C-SBRT) for Higher Risk Early Stage Lung Cancer, G751769148, G788993117, Physics and Biology of FLASH Radiation, G8577543746, G9000005307, G9000034222, G9000043691, G9000102198, G9000172281, G9000201487, G9000222134, G9000282359, G9000283078, Translational Studies in FLASH Particle Radiotherapy, G983272094
OpenAlex ID: W4367301480