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Insurer or self-insured employer's plans are increasingly using copay accumulator, copay maximizer, and alternative funding programs (AFPs) to reduce plan spending on high-priced prescriptions. These programs differ in their structure and impact on patient affordability but typically decrease the insurer or self-insured employer's financial responsibility for high-priced drugs and increase the complexity of specialty medication access for patients. The aim of this primer is to describe the structure of copay accumulator, copay maximizer, and AFPs to improve understanding of these cost-shifting strategies and help clinicians and patients navigate medication access and affordability issues to minimize treatment delays or non-initiation.
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Seguro de Servicios Farmacéuticos , Humanos , Seguro de Servicios Farmacéuticos/economía , Costos de los Medicamentos , Seguro de Costos Compartidos/economía , Deducibles y Coseguros/economía , Medicamentos bajo Prescripción/economíaRESUMEN
This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of tumor radiobiology, normal tissue constraints, and treatment planning with LET and RBE considerations is then reviewed. Part 2 summarizes current and past clinical data and then suggests the next steps to explore and employ tools for improved dynamic models for RBE. In part 3, approaches and methods for the next generation of prospective clinical trials are explored, with the goal of optimizing RBE to be both more reflective of clinical reality and also deployable in trials to allow clinical validation and interpatient comparisons. These concepts provide the foundation for personalized biologic treatments reviewed in part 4. Finally, we conclude with a summary including short- and long-term scientific focus points for clinical PT. The practicalities and capacity to use RBE in treatment planning are reviewed and considered with more biological data in hand. The intermediate step of LET optimization is summarized and proposed as a potential bridge to the ultimate goal of case-specific RBE planning that can be achieved as a hypothesis-generating tool in near-term proton trials.
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Purpose: To report the current practice pattern of the proton stereotactic body radiation therapy (SBRT) for prostate treatments. Materials and Methods: A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in February, 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and image-guided radiation therapy (IGRT) methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited 3 primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and magnetic resonance imaging (MRI) for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35 to 40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.
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A solid understanding of fractions is the cornerstone for acquiring proficiency with rational numbers and paves the way for learning advanced mathematical concepts such as algebra. Fraction difficulties limit not only students' educational and vocational opportunities but also their ability to solve everyday problems. Students who exit sixth grade with inadequate understanding of fractions may experience far-reaching repercussions that lead to lifelong avoidance of mathematics. This article presents the results of a randomized controlled trial focusing on the first two cohorts of a larger efficacy investigation aimed at building fraction sense in students with mathematics difficulties. Teachers implemented an evidence-informed fraction sense intervention (FSI) within their sixth-grade intervention classrooms. The lessons draw from research in cognitive science as well as mathematics education research. Employing random assignment at the classroom level, multilevel modeling revealed a significant effect of the intervention on posttest fractions scores after controlling for pretest fractions scores, working memory, vocabulary, proportional reasoning, and classroom attentive behavior. Students in the FSI group outperformed their counterparts in the control group, with noteworthy effect sizes on most fraction measures. Challenges associated with carrying out school-based intervention research are addressed.
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Matemática , Instituciones Académicas , Humanos , Masculino , Femenino , Niño , Matemática/educación , Estudiantes/psicología , Solución de Problemas , Discalculia/psicologíaRESUMEN
Objective. This study characterized optically-stimulated luminescent dosimeter (OSLD) nanoDots for use in a therapeutic carbon beam using the Imaging and Radiation Oncology Core (IROC) framework for remote output verification.Approach. The absorbed dose correction factors for OSLD (fading, linearity, beam quality, angularity, and depletion), as defined by AAPM TG 191, were characterized for carbon beams. For the various correction factors, the effect of linear energy transfer (LET) was examined by characterizing in both a low and high LET setting.Main results. Fading was not statistically different between reference photons and carbon, nor between low and high LET beams; thus, the standard IROC-defined exponential function could be used to characterize fading. Dose linearity was characterized with a linear fit; while low and high LET carbon linearity was different, these differences were small and could be rolled into the uncertainty budget if using a single linearity correction. A linear fit between beam quality and dose-averaged LET was determined. The OSLD response at various angles of incidence was not statistically different, thus a correction factor need not be applied. There was a difference in depletion between low and high LET irradiations in a primary carbon beam, but this difference was small over the standard five readings. The largest uncertainty associated with the use of OSLDs in carbon was because of thekQcorrection factor, with an uncertainty of 6.0%. The overall uncertainty budget was 6.3% for standard irradiation conditions.Significance. OSLD nanoDot response was characterized in a therapeutic carbon beam. The uncertainty was larger than for traditional photon applications. These findings enable the use of OSLDs for carbon absorbed dose measurements, but with less accuracy than conventional OSLD audit programs.
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Carbono , Carbono/química , Carbono/uso terapéutico , Radiometría/métodos , Transferencia Lineal de Energía , Incertidumbre , Dosimetría con Luminiscencia Ópticamente Estimulada/métodos , Dosificación Radioterapéutica , HumanosRESUMEN
PURPOSE: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam. METHODS: Eight materials were tested for radiological material-equivalence in a carbon ion beam. The materials were computed tomography (CT)-scanned to obtain Hounsfield unit (HU) values, then irradiated in a monoenergetic carbon ion beam to determine relative linear stopping power (RLSP). The corresponding HU and RLSP for each phantom material were compared to clinical carbon ion calibration curves. For absorbed dose comparison, ion chamber measurements were made in the center of a carbon ion spread-out Bragg peak (SOBP) in water and in the phantom material, evaluating whether the material perturbed the absorbed dose measurement beyond what was predicted by the HU-RLSP relationship. RESULTS: Polyethylene, solid water (Gammex and Sun Nuclear), Blue Water (Standard Imaging), and Techtron HPV had measured RLSP values that agreed within ±4.2% of RLSP values predicted by the clinical calibration curve. Measured RLSP for acrylic was 7.2% different from predicted. The agreement for balsa wood and cork varied between samples. Ion chamber measurements in the phantom materials were within 0.1% of ion chamber measurements in water for most materials (solid water, Blue Water, polyethylene, and acrylic), and within 1.9% for the rest of the materials (balsa wood, cork, and Techtron HPV). CONCLUSIONS: Several phantom materials (Blue Water, polyethylene, solid water [Gammex and Sun Nuclear], and Techtron HPV) are suitable for heterogeneous phantom measurements for carbon ion therapy. Low density materials should be carefully characterized due to inconsistencies between samples.
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Radioterapia de Iones Pesados , Fantasmas de Imagen , Radioterapia de Iones Pesados/instrumentación , Calibración , Tomografía Computarizada por Rayos X , HumanosRESUMEN
A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in Feb. 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and IGRT methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited three primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and MRI for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35-40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.
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Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally-fractionated PBSPT due to concerns of amplified uncertainties at the larger dose per fraction. NRG Oncology and Particle Therapy Cooperative Group (PTCOG) Thoracic Subcommittee surveyed US proton centers to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Amongst other points, the recommendations highlight the need for volumetric image guidance and multiple CT-based robust optimization and robustness tools to minimize further the impact of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques.
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Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques.
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Consenso , Terapia de Protones , Hipofraccionamiento de la Dosis de Radiación , Radiocirugia , Neoplasias Torácicas , Terapia de Protones/métodos , Humanos , Radiocirugia/métodos , Neoplasias Torácicas/radioterapia , Órganos en Riesgo/efectos de la radiación , Oncología por Radiación/normas , Pautas de la Práctica en Medicina , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Estados Unidos , Tomografía Computarizada por Rayos X , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagenRESUMEN
BACKGROUND: Daily IGRT images show day-to-day anatomical variations in patients undergoing fractionated prostate radiotherapy. This is of particular importance in particle beam treatments. PURPOSE: To develop a digital phantom series showing variation in pelvic anatomy for evaluating treatment planning and IGRT procedures in particle radiotherapy. METHODS: A pelvic phantom series was developed from the planning MRI and kVCT (planning CT) images along with six of the daily serial MVCT images taken of a single patient treated with a full bladder on a Tomotherapy unit. The selected patient had clearly visible yet unexceptional internal anatomy variation. Prostate, urethra, bladder, rectum, bowel, bowel gas, bone and soft tissue were contoured and a single Hounsfield Unit was assigned to each region. Treatment plans developed on the kVCT for photon, proton and carbon beams were recalculated on each phantom to demonstrate a clinical application of the series. Proton plans were developed with and without robust optimization. RESULTS: Limited to axial slices with prostate, the bladder volume varied from 6 to 46 cm3, the rectal volume (excluding gas) from 22 to 52 cm3, and rectal gas volume from zero to 18 cm3. The water equivalent path length to the prostate varied by up to 1.5 cm . The variations resulted in larger changes in the RBE-weighted Dose Volume Histograms of the non-robust proton plan and the carbon plan compared to the robust proton plan, the latter similar to the photon plan. The prostate coverage (V100%) decreased by an average of 18% in the carbon plan, 16% in the non-robust proton plan, 1.8% in the robust proton plan, and 4.4% in the photon plan. The volume of rectum receiving 75% of the prescription dose (V75%) increased by an average of 3.7 cm3, 4.7 cm3, 1.9 cm3, and 0.6 cm3 in those four plans, respectively. CONCLUSIONS: The digital pelvic phantom series provides for quantitative investigation of IGRT procedures and new methods for improving accuracy in particle therapy and may be used in cross-institutional comparisons for clinical trial quality assurance.
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Neoplasias de la Próstata , Terapia de Protones , Radioterapia de Intensidad Modulada , Humanos , Masculino , Protones , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Recto/diagnóstico por imagen , Radioterapia de Intensidad Modulada/métodos , Pelvis/diagnóstico por imagen , Fraccionamiento de la Dosis de Radiación , Carbono , Dosificación Radioterapéutica , Terapia de Protones/métodosRESUMEN
Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better treatment plan optimization and more accurate dose calculation. We expect to re-start the SBPT program, including for early stage NSCLC as well as for other disease sites soon after starting patient treatment at our new proton therapy center.
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Purpose: To analyze trends in institutional performance and failure modes for the Imaging and Radiation Oncology Core's (IROC's) proton liver phantom. Materials and Methods: Results of 66 phantom irradiations from 28 institutions between 2015 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom results. Phantom results included pass/fail classification, average thermoluminescent dosimeter (TLD) ratio of both targets, and percentage of pixels passing gamma of both targets. The following categories were evaluated in terms of how they predicted these outcomes: irradiation year, treatment planning system (TPS), TPS algorithm, treatment machine, number of irradiations, treatment technique, motion management technique, number of isocenters, and superior-inferior extent (in cm) of the 90% TPS isodose line for primary target 1 (PTV1) and primary target 2 (PTV2). In addition, failures were categorized by failure mode. Results: Average pass rate was approximately 52% and average TLD ratio for both targets had slightly improved. As the treatment field increased to cover the target, the pass rate statistically significantly fell. Lower pass rates were observed for Mevion machines, scattered irradiation techniques, and gating and internal target volume (ITV) motion management techniques. Overall, the accuracy of the random forest modeling of the phantom results was approximately 73% ± 14%. The most important predictor was the superior-inferior extent for both targets and irradiation year. Three failure modes dominated the failures of the phantom: (1) systematic underdosing, (2) poor localization in the superior-inferior direction, and (3) range error. Only 44% of failures have similar failure modes between the 2 targets. Conclusion: Improvement of the proton liver phantom has been observed; however, the pass rate remains the lowest among all IROC phantoms. Through various analysis techniques, range uncertainty, motion management, and underdosing are the main culprits of failures of the proton liver phantom. Clinically, careful consideration of the influences of liver proton therapy is needed to improve phantom performance and patient outcome.
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Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the Henipavirus genus within the paramyxovirus family and are harbored by Pteropus Flying Fox species. Henipaviruses cause severe respiratory disease, neural symptoms, and encephalitis in various animals and humans, with human mortality rates exceeding 70% in some NiV outbreaks. The henipavirus matrix protein (M), which drives viral assembly and budding of the virion, also performs non-structural functions as a type I interferon antagonist. Interestingly, M also undergoes nuclear trafficking that mediates critical monoubiquitination for downstream cell sorting, membrane association, and budding processes. Based on the NiV and HeV M X-ray crystal structures and cell-based assays, M possesses a putative monopartite nuclear localization signal (NLS) (residues 82KRKKIR87; NLS1 HeV), positioned on an exposed flexible loop and typical of how many NLSs bind importin alpha (IMPα), and a putative bipartite NLS (244RR-10X-KRK258; NLS2 HeV), positioned within an α-helix that is far less typical. Here, we employed X-ray crystallography to determine the binding interface of these M NLSs and IMPα. The interaction of both NLS peptides with IMPα was established, with NLS1 binding the IMPα major binding site, and NLS2 binding as a non-classical NLS to the minor site. Co-immunoprecipitation (co-IP) and immunofluorescence assays (IFA) confirm the critical role of NLS2, and specifically K258. Additionally, localization studies demonstrated a supportive role for NLS1 in M nuclear localization. These studies provide additional insight into the critical mechanisms of M nucleocytoplasmic transport, the study of which can provide a greater understanding of viral pathogenesis and uncover a potential target for novel therapeutics for henipaviral diseases.
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Virus Hendra , Infecciones por Henipavirus , Virus Nipah , Animales , Humanos , Señales de Localización Nuclear/metabolismo , Transporte Activo de Núcleo Celular , alfa Carioferinas/metabolismo , Unión ProteicaRESUMEN
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.
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Habilitación Profesional , Electrones , Humanos , Instituciones de Salud , Posicionamiento del Paciente , Tecnología , Dosificación RadioterapéuticaRESUMEN
BACKGROUND AND PURPOSE: The Global Clinical Trials RTQA Harmonization Group (GHG) set out to evaluate and prioritize clinical trial quality assurance. METHODS: The GHG compiled a list of radiotherapy quality assurance (QA) tests performed for proton and photon therapy clinical trials. These tests were compared between modalities to assess whether there was a need for different types of assessments per modality. A failure modes and effects analysis (FMEA) was performed to assess the risk of each QA failure. RESULTS: The risk analysis showed that proton and photon therapy shared four out of five of their highest-risk failures (end-to-end anthropomorphic phantom test, phantom tests using respiratory motion, pre-treatment patient plan review of contouring/outlining, and on-treatment/post-treatment patient plan review of dosimetric coverage). While similar trends were observed, proton therapy had higher risk failures, driven by higher severity scores. A sub-analysis of occurrence × severity scores identified high-risk scores to prioritize for improvements in RTQA detectability. A novel severity scaler was introduced to account for the number of patients affected by each failure. This scaler did not substantially alter the ranking of tests, but it elevated the QA program evaluation to the top 20th percentile. This is the first FMEA performed for clinical trial quality assurance. CONCLUSION: The identification of high-risk errors associated with clinical trials is valuable to prioritize and reduce errors in radiotherapy and improve the quality of trial data and outcomes, and can be applied to optimize clinical radiotherapy QA.
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Análisis de Modo y Efecto de Fallas en la Atención de la Salud , Protones , Humanos , Fotones/uso terapéutico , Radiometría , Medición de RiesgoRESUMEN
Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters. Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted outcomes: year of irradiation, TPS algorithm, machine model, energy, and delivered field size. Results: Overall, only 84.6% of irradiations have met the IROC/NCI acceptability criteria. Pass rate has remained constant over time, while dose calculation accuracy has slightly improved. Dose calculation algorithm (P < .001), collimator (P = .024), and field size (P < .001) were statistically significant predictors of pass/fail. Specifically, pencil beam algorithms and cone collimators were more likely to be associated with failing phantom results. Random forest modeling identified the size of the field as the most important factor for passing or failing followed by algorithm. Conclusion: Constant throughout this retrospective study, approximately 15% of institutions fail to meet IROC/NCI standards for SRS treatment. In current clinical practice, this is particularly associated with smaller fields that yielded less accurate results. There is ongoing need to improve small field dosimetry, beam modeling, and QA to ensure high treatment quality, patient safety, and optimal clinical trials.
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While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous dosimetry, 3D treatment planning, volumetric image guidance, or motion management, may play a major role in defining how to use, or whether to use, FLASH radiotherapy. Given the extended time frame for patients to experience late effects, we recommend moving deliberately but cautiously forward toward clinical trials. In this paper, we review the state of quality assurance and safety systems in FLASH, identify critical pre-clinical data points that need to be defined, and suggest how lessons learned from previous technological advancements will help us close the gaps and build a successful path to evidence-driven FLASH implementation.
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Terapia de Protones , Oncología por Radiación , Ensayos Clínicos como Asunto , Habilitación Profesional , Humanos , Radiobiología , Dosificación RadioterapéuticaRESUMEN
PURPOSE: The current distribution of radiation therapy (RT) facilities in the United States is not well established. A comprehensive inventory of U.S. RT facilities was last assessed in 2005, based on data from state regulatory agencies and dosimetric quality assurance bodies. We updated this database to characterize population-level measures of geographic access to RT and analyze changes over the past 15 years. METHODS AND MATERIALS: We compiled data from regulatory and accrediting organizations to identify U.S. facilities with linear accelerators used to treat humans in 2018 to 2020. Addresses were geocoded and analyzed with Geographic Information Services software. Geographic access was characterized by assessing the Euclidian distance between ZIP code tabulation areas/county centroids and RT facilities. Populations were assigned to each county to estimate the effect of facility changes at the population level. Logistic regressions were performed to identify features associated with increased distance to RT and associated with regions that gained an RT facility between the 2 time points studied. RESULTS: In 2020, a total of 2313 U.S. RT facilities were reported, compared with 1987 in 2005, representing a 16.4% growth in facilities over nearly 15 years. Based on population attribution to the centroids of ZIP Code Tabulation Areas, 77.9% of the U.S. population lives within 12.5 miles of an RT facility, and 1.8% of the U.S. population lives more than 50 miles from an RT facility. We found that increased distance to RT was associated with nonmetro status, less insurance, older median age, and less populated regions. Between 2005 and 2020, the population living within 12.5 miles from an RT facility increased by 2.1 percentage points, whereas the population living furthest from RT facilities decreased 0.6 percentage points. Regions with improved geographic RT access are more likely to be higher income and better insured. CONCLUSIONS: The percentage of the U.S. population with limited geographic access to RT is 1.8%. We found that people benefiting from improved access to RT facilities are more economically advantaged, suggesting disparities in geographic access may not improve without intervention.