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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Estimates of Alpha/Beta (α/β) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial

Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Simultaneous Targeting of RSK and AKT Efficiently Inhibits YB-1-Mediated Repair of Ionizing Radiation-Induced DNA Double-Strand Breaks in Breast Cancer Cells

Y-box binding protein 1 (YB-1) overexpression is associated with chemotherapy- and radiation therapy resistance. Ionizing radiation (IR), receptor tyrosine kinase ligands, and mutation in KRAS gene stimulate activation of YB-1. YB-1 accelerates the repair of IR-induced DNA double-strand breaks (DSBs). Ribosomal S6 kinase (RSK) is the main kinase inducing YB-1 phosphorylation. We investigated the impact of RSK targeting on DSB repair and radiosensitivity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2010

A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

Hu, Shaowen↗
DOE OSTI2021

Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model

Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Quantitating Interfraction Target Dynamics During Concurrent Chemoradiation for Glioblastoma: A Prospective Serial Imaging Study

Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Lung Cancer and Heart Disease Risks Associated With Low-Dose Pulmonary Radiotherapy to COVID-19 Patients With Different Background Risks

The respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Because treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiation therapy is being evaluated as an anti-inflammatory modality. However, there is concern about the long-term risks associated with low-dose pulmonary irradiation. To help quantify the benefit-risk balance of low-dose radiation therapy for COVID-19, we estimated radiation-induced lifetime risks of both lung cancer and heart disease (major coronary events) for patients of different sexes, treated at ages 50 to 85, with and without other relevant risk factors (cigarette smoking and baseline heart disease risk).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Regulatory Considerations in the Development of Radiation-Drug Combinations

Radiation therapy remains a fundamental treatment for patients with cancer. Despite an increasing number of targeted molecular therapies that are US Food and Drug Administration (FDA)-approved for the treatment of patients with metastatic disease, there has been very little progress made in terms of drugs used concurrently with radiation. This article reviews the existing regulatory framework in which cancer drugs may be developed for use in combination with radiation therapy from the perspective of the FDA. To briefly summarize: (1) nonclinical studies are a critical first step to ensure that drugs are safe for use in humans; however, additional nonclinical studies of a drug with radiation may not be required before a clinical trial in combination with radiation as long as the safety profile of the drug has been characterized in humans. The FDA determines the quality of evidence required before studying a drug in combination with radiation on a case-by-case basis. (2) Although often impractical to consider late toxicities during dose-escalation, late adverse events should be captured and taken into consideration when determining the final dose and schedule to take forward during drug development. (3) There are a number of expedited programs for cancer drug development, including accelerated approval, a conditional approval that allows for use of earlier clinical endpoints when the data suggests a clinically meaningful improvement over available therapy. (4) The Agency encourages sponsors to discuss their development plan with the appropriate FDA review division in formal regulatory meetings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Ultra-high-dose-rate FLASH and Conventional-Dose-Rate Irradiation Differentially Affect Human Acute Lymphoblastic Leukemia and Normal Hematopoiesis

Ultra-high-dose-rate FLASH radiation therapy has been shown to minimize side effects of irradiation in various organs while keeping antitumor efficacy. This property, called the FLASH effect, has caused enthusiasm in the radiation oncology community because it opens opportunities for safe dose escalation and improved radiation therapy outcome. Here, we investigated the impact of ultra-high-dose-rate FLASH versus conventional-dose-rate (CONV) total body irradiation (TBI) on humanized models of T-cell acute lymphoblastic leukemia (T-ALL) and normal human hematopoiesis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Monte Carlo simulation of shielding designs for a cabinet form factor preclinical MV–energy photon FLASH radiotherapy system

Purpose: A preclinical MV-energy photon FLASH radiotherapy system is being designed at Stanford and SLAC National Accelerator Laboratory. Because of the higher energy and dose rate compared to conventional kV-energy photon laboratory-scale irradiators, adequate shielding in a stand-alone cabinet form factor is more challenging to achieve. We present a Monte Carlo simulation of multilayered shielding for a compact self-shielding system without the need for a radiation therapy vault. Methods: A multilayered shielding approach using multiple alternating layers of high-Z and low-Z materials is applied to the self-shielded cabinet to effectively mitigate the secondary radiation produced and to allow the device to be housed in a Controlled Radiation Area outside of a radiation vault. The multilayered shielding approach takes advantage of the properties of high-Z and low-Z radiation shielding materials such as density, cross-section, atomic number of the shielding elements, and products of radiation interactions within each layer. The Monte Carlo radiation transport code, FLUKA, is used to simulate the total effective dose produced by the operation. Results: The multilayered shielding designs proposed and simulated produced effective dose rates significantly lower than monolayer designs with the same total material thickness at the regulatory boundary; this is accomplished through the manipulation of the locations where secondary radiation is produced and reactions due to material properties such as neutron back reflection in hydrogen. Borated polyethylene at 5 wt% significantly increased the shielding performance as compared to regular polyethylene, with the magnitude of the reduction depending upon the order of the shielding material. Conclusions: The multilayered shielding provides a path for shielding preclinical FLASH systems that deliver MV-energy bremsstrahlung photons. Furthermore, this approach promises to be more efficient with respect to the shielding material mass and space claim as compared to shielded vaults typically required for clinical radiation therapy with MV photons.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2008

Using Light to Treat Mucositis and Help Wounds Heal

A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

Ignatius, Robert W.↗
DOE OSTI2021

Combining Clinical and Dosimetric Features in a PBS Proton Therapy Cohort to Develop a NTCP Model for Radiation-Induced Optic Neuropathy

Radiation-induced optic neuropathy (RION) is a rare, yet severe complication following radiation therapy for brain, head and neck, or skull-base tumors. Although several risk factors, such as age, metabolic syndrome, and delivered dose, have been identified, we aimed at expanding the understanding of the mechanisms of interplay regarding dosimetry and patient variables leading to the onset of RION with a focus on proton therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Patient-Reported Outcomes in the Acute Phase of the Randomized Hypofractionated Irradiation for Prostate Cancer (HYPRO) Trial

Many patients experience bowel and bladder toxicity during the acute phase of radiation therapy for prostate cancer. Recent literature indicates that hypofractionation (HF) might increase this acute response but little is known on patient-reported outcome during this phase with HF. We evaluated the course of patient-reported acute symptoms during HF versus standard fractionated (SF) radiation therapy within the hypofractionated irradiation for prostate cancer (HYPRO) trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Optimizing Treatment in Intermediate-Risk Prostate Cancer: Secondary Analysis of a Randomized Phase 3 Trial

To identify patients with intermediate-risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiation therapy (DERT), we performed a secondary analysis of a phase 3 trial by measuring biochemical failure (BF), distant metastases, prostate cancer–specific mortality, overall survival (OS), and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RT with passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS1997

Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes

Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

NASA Center JSC↗
DOE OSTI2021

Safety Margins for the Delineation of the Left Anterior Descending Artery in Patients Treated for Breast Cancer

Cardiac toxicity after breast cancer (BC) radiation therapy is partly due to the large radiation doses to coronary arteries. The left anterior descending artery (LAD) is particularly exposed. A first step in achieving robust dose constraints to the LAD during treatment planning is homogeneous delineation based on guidelines. LAD delineation can be problematic due to heart movements. The aim of the study was to establish a safety margin for delineation of the LAD in patients with BC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗