Biological Effective Dose as a Predictor of Hypopituitarism After Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis and Cohort Study of Patients Treated Using Contemporary Techniques.

BACKGROUND: Hypopituitarism is the most frequent complication after pituitary adenoma stereotactic radiosurgery (SRS) and is correlated with increasing radiation to the pituitary gland. Biological effective dose (BED) is a dosimetric parameter that incorporates a time component to adjust for mechanisms of deoxyribonucleic acid repair activated during treatment. OBJECTIVE: To assess mean gland BED as a predictor of post-SRS hypopituitarism, as compared to mean gland dose, in a contemporary cohort study of patients undergoing single-fraction SRS for pituitary adenoma. METHODS: Cohort study of 97 patients undergoing single-fraction SRS from 2007 to 2014. Eligible patients had no prior pituitary irradiation, normal pre-SRS endocrine function, and >24 mo of endocrine follow-up. Cox proportional hazards analysis was used to assess mean gland dose and BED as predictors of new post-SRS hypopituitarism. RESULTS: Median post-SRS follow-up was 48 mo (interquartile range [IQR], 34-68). A total of 27 patients (28%) developed new hypopituitarism at a median 22 mo (IQR, 12-36). Actuarial rates of new endocrinopathy were 17% at 2 yr (95% CI 10%-25%) and 31% at 5 yr (95% CI 20%-42%). On univariate analysis, sex (P = .02), gland volume (P = .03), mean gland dose (P < .0001), and BED significantly predicted new hypopituitarism (P < .0001). After adjusting for sex and gland volume, BED > 45 Gy2.47 and mean gland dose > 10 Gy were significantly associated increased risk of hypopituitarism (hazard ratio [HR] = 14.32, 95% CI = 4.26-89.0, P < .0001; HR = 11.91, 95% CI = 3.54-74.0, P < .0001). CONCLUSION: BED predicted hypopituitarism more reliably than mean gland dose after pituitary adenoma SRS, but additional studies are needed to confirm these results.

The hunt for radiation biomarkers: current situation.

Purpose: The possibility of a large-scale acute radiation exposure necessitates the development of new methods that could provide a rapid assessment of the doses received by individuals using high-throughput technologies. There is also a great interest in developing new biomarkers of dose exposure, which could be used in large molecular epidemiological studies in order to correlate estimated doses received and health effects. The goal of this review was to summarize current literature focused on biological dosimetry, namely radiation-responsive biomarkers.Methods: The studies involved in this review were thoroughly selected according to the determined criteria and PRISMA guidelines.Results: We described briefly recent advances in radiation genomics and metabolomics, giving particular emphasis to proteomic analysis. The majority of studies were performed on animal models (rats, mice, and non-human primates). They have provided much beneficial information, but the most relevant tests have been done on human (oncological) patients. By inspecting the radiaiton biodosimetry literate of the last 10 years, we identified a panel of candidate markers for each -omic approach involved.Conslusions: We reviewed different methodological approaches and various biological materials, which can be exploited for dose-effect prediction. The protein biomarkers from human plasma are ideal for this specific purpose. From a plethora of candidate markers, FDXR is a very promising transcriptomic candidate, and importantly this biomarker was also confirmed by some studies at protein level in humans.

A Review: Photonic Devices Used for Dosimetry in Medical Radiation.

Numerous instruments such as ionization chambers, hand-held and pocket dosimeters of various types, film badges, thermoluminescent dosimeters (TLDs) and optically stimulated luminescence dosimeters (OSLDs) are used to measure and monitor radiation in medical applications. Of recent, photonic devices have also been adopted. This article evaluates recent research and advancements in the applications of photonic devices in medical radiation detection primarily focusing on four types; photodiodes - including light-emitting diodes (LEDs), phototransistors-including metal oxide semiconductor field effect transistors (MOSFETs), photovoltaic sensors/solar cells, and charge coupled devices/charge metal oxide semiconductors (CCD/CMOS) cameras. A comprehensive analysis of the operating principles and recent technologies of these devices is performed. Further, critical evaluation and comparison of their benefits and limitations as dosimeters is done based on the available studies. Common factors barring photonic devices from being used as radiation detectors are also discussed; with suggestions on possible solutions to overcome these barriers. Finally, the potentials of these devices and the challenges of realizing their applications as quintessential dosimeters are highlighted for future research and improvements.

Personal Radiation Protection and Corresponding Dosimetry in Interventional Radiology: An Overview and Future Developments. / Persönliche Strahlenschutzmittel und Dosimetrie des medizinischen Personals in der interventionellen Radiologie: Aktueller Status und neue Entwicklungen.

BACKGROUND: The increasing number of minimally invasive fluoroscopy-guided interventions is likely to result in higher radiation exposure for interventional radiologists and medical staff. Not only the number of procedures but also the complexity of these procedures and therefore the exposure time as well are growing. There are various radiation protection means for protecting medical staff against scatter radiation. This article will provide an overview of the different protection devices, their efficacy in terms of radiation protection and the corresponding dosimetry. METHOD: The following key words were used to search the literature: radiation protection, eye lens dose, radiation exposure in interventional radiology, cataract, cancer risk, dosimetry in interventional radiology, radiation dosimetry. RESULTS AND CONCLUSION: Optimal radiation protection always requires a combination of different radiation protection devices. Radiation protection and monitoring of the head and neck, especially of the eye lenses, is not yet sufficiently accepted and further development is needed in this field. To reduce the risk of cataract, new protection glasses with an integrated dosimeter are to be introduced in clinical routine practice. KEY POINTS: · A combination of personal radiation protection devices and optimized dosimetry improves the safety of medical staff.. CITATION FORMAT: · König AM, Etzel R, Thomas RP et al. Personal Radiation Protection and Corresponding Dosimetry in Interventional Radiology: An Overview and Future Developments. Fortschr Röntgenstr 2019; 191: 512 - 521.

Uses of Effective Dose: The Good, the Bad, and the Future.

Effective dose (E) is a risk-adjusted dosimetric quantity developed by the International Commission on Radiological Protection. It is a key metric for practical management of the risk of stochastic health effects in a comprehensive radiation protection program. The International Commission on Radiological Protection and others have emphasized repeatedly that E is not intended to represent an actual radiation dose and should not be used as a risk-related metric for a specific person or population. The cancer risk uncertainties in the low-dose range and the underlying approximations, simplifications, and sex- and age-averaging used in generating E make it unsuitable for this purpose. However, in practice, medical imaging professionals and authors of peer-reviewed medical publications frequently and incorrectly use E as a surrogate for whole-body dose in order to calculate cancer risk estimates for specific patients or patient populations. This frequent misuse has popularized E for uses for which it was neither designed nor intended. Alternatives to E have been proposed that attempt to account for known age and sex differences in radiation sensitivity. E has also been proposed as a general indicator for communicating radiation risk to patients, if its limitations are kept in mind. Forthcoming guidance from the International Commission on Radiological Protection will likely clarify if, when, and how some form of E may be used as a rough indicator of the risk of a stochastic effect, possibly with some modifications for the substantial variations in risk known to exist with respect to age, sex, and population group.

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer

Purpose. This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. Methods. 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. Results. Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V20 was associated with lower WBC nadir. Increased LSBM-V40 was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V40 was found. Patients with LSBM-V40 ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01). Conclusions. Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V40 was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V40 could be used to limit HT (AU)

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THE DECADE OF THE RABiT (2005-15).

The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with 'off the shelf' systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies.

Organ Doses From Diagnostic Medical Radiography-Trends Over Eight Decades (1930 to 2010).

This study provides a retrospective assessment of doses to 13 organs for the most common radiographic examinations conducted between the 1930s and 2010, taking into account typical technical parameters used for radiography during those years. This study is intended to be a resource on changes in medical diagnostic radiation exposure over time with a specific purpose of supporting retrospective epidemiological studies of radiation health risks. The authors derived organ doses to the brain, esophagus, thyroid, red bone marrow, lungs, breast, heart, stomach, liver, colon, urinary bladder, ovaries, and testes based on 14 common radiographic procedures and compared, when possible, with doses reported in the literature. These dose estimates were based on radiographic exposure parameters described in textbooks widely used by radiologic technologists in training from 1939 to 2010. The derived estimated doses presented here are believed to be representative of typical organs for an average-size adult who might be considered to be similar to the reference person. There were large variations in organ doses noted among the different types of radiographic examinations. Doses were highest in organs within the area imaged and next highest in organs in close proximity to the area imaged. Estimated organ doses have declined substantially [overall 22-fold (±38)] over time as a consequence of changes in technology, imaging protocols and protective measures. For some examinations, only slight differences were observed in doses for the decades of the 1960s, 1970s, and 1980s due to minor changes in technical parameters. Substantial dose reductions were observed in the 1990s and 2000s.

Yttrium-90 hepatic radioembolization: clinical review and current techniques in interventional radiology and personalized dosimetry.

In recent years, yttrium-90 ((90)Y) microsphere radioembolization has been establishing itself as a safe and efficacious treatment for both primary and metastatic liver cancers. This extends to both first-line therapies as well as in the salvage setting. In addition, radioembolization appears efficacious for patients with portal vein thrombosis, which is currently a contraindication for surgery, transplantation and transarterial chemoembolization. This article reviews the efficacy and expanding use of (90)Y microsphere radioembolization with an added emphasis on recent advances in personalized dosimetry and interventional radiology techniques. Directions for future research into combination therapies with radioembolization and expansion into sites other than the liver are also explored.

Urgent Change Needed to Radiation Protection Policy.

Although almost 120 y of medical experience and data exist on human exposure to ionizing radiation, advisory bodies and regulators claim there are still significant uncertainties about radiation health risks that require extreme precautions be taken. Decades of evidence led to recommendations in the 1920s for protecting radiologists by limiting their daily exposure. These were shown in later studies to decrease both their overall mortality and cancer mortality below those of unexposed groups. In the 1950s, without scientific evidence, the National Academy of Sciences Biological Effects of Atomic Radiation (BEAR) Committee and the NCRP recommended that the linear no-threshold (LNT) model be used to assess the risk of radiation-induced mutations in germ cells and the risk of cancer in somatic cells. This policy change was accepted by the regulators of every country without a thorough review of its basis. Because use of the LNT model has created extreme public fear of radiation, which impairs vital medical applications of low-dose radiation in diagnostics and therapy and blocks nuclear energy projects, it is time to change radiation protection policy back into line with the data.

Future of Radiation Protection Regulations.

THERE IS considerable disagreement in the scientific community regarding the carcinogenicity of low-dose radiation (LDR), with publications supporting opposing points of view. However, major flaws have been identified in many of the publications claiming increased cancer risk from LDR. The data generally recognized as the most important for assessing radiation effects in humans, the atomic bomb survivor data, are often cited to raise LDR cancer concerns. However, these data no longer support the linear no-threshold (LNT) model after the 2012 update but are consistent with radiation hormesis. Thus, a resolution of the controversy regarding the carcinogenicity of LDR appears to be imminent, with the rejection of the LNT model and acceptance of radiation hormesis. Hence, for setting radiation protection regulations, an alternative approach to the present one based on the LNT model is needed. One approach would be to determine the threshold dose for the carcinogenic effect of radiation from existing data and establish regulations to ensure radiation doses are kept well below the threshold dose. This can be done by setting dose guidelines specifying safe levels of radiation doses, with the requirement that these safe levels, referred to as guidance levels, not be exceeded significantly. Using this approach, a dose guidance level of 10 cGy for acute radiation exposures and 10 cGy y for exposures over extended periods of time are recommended. The concept of keeping doses as low as reasonably achievable, known as ALARA, would no longer be required for low-level radiation exposures not expected to exceed the dose guidance levels significantly. These regulations would facilitate studies using LDR for prevention and treatment of diseases. Results from such studies would be helpful in refining dose guidance levels. The dose guidance levels would be the same for the public and radiation workers to ensure everyone's safety.

An investigation of the potential causes for the seasonal and annual variations in indoor radon concentrations.

Indoor radon concentrations exhibit strong variations on short and long timescales. Besides human influences, meteorological factors significantly affect the radon concentrations indoors as well as outdoors. In this article, long-term measurements showing strong annual variations are presented, which take a very similar course in different buildings located in largely separated regions in Switzerland. Also, seasonal variations can be very significant. In general, variations in indoor radon levels can primarily be attributed to human influences. On the other hand, specific weather conditions can have a significant impact on indoor radon levels. In order to further investigate the connection between indoor radon levels and meteorological factors, a measuring campaign has been started in two buildings located in two different regions in Switzerland exhibiting different climatic characteristics. Preliminary results of these investigations are presented, which provide evidence for correlations between indoor radon levels and in particular outdoor temperatures, contributing to seasonal and annual as well as short-term variations in indoor radon concentrations.

The future of medical dosimetry.

The world of health care delivery is becoming increasingly complex. The purpose of this manuscript is to analyze current metrics and analytically predict future practices and principles of medical dosimetry. The results indicate five potential areas precipitating change factors: a) evolutionary and revolutionary thinking processes, b) social factors, c) economic factors, d) political factors, and e) technological factors. Outcomes indicate that significant changes will occur in the job structure and content of being a practicing medical dosimetrist. Discussion indicates potential variables that can occur within each process and change factor and how the predicted outcomes can deviate from normative values. Finally, based on predicted outcomes, future opportunities for medical dosimetrists are given.

Looking into future: challenges in radiation protection in medicine.

Radiation protection in medicine is becoming more and more important with increasing wider use of X-rays, documentation of effects besides the potential for long-term carcinogenic effects. With computed tomography (CT) likely to become sub-mSv in coming years, positron emission tomography (PET), single photon emission computed tomography (SPECT) and some of the nuclear medical examination will become focus of attraction as high-dose examinations, even though they are less-frequent ones. Clarity will be needed on radiation effects at levels of radiation doses encountered in a couple of CT scans and if effects are really cumulative. There is challenge to develop radiation metrics that can be used as easily as units of temperature and length and avoidance of multiple meaning of a single dose metric. Other challenges include development of biological indicators of radiation dose, transition from dose to a representative phantom to dose to individual patient, system for tracking of radiation exposure history of patient, avoidance of radiation-induced skin injury in patients and radiation cataract in staff, cutting down inappropriate referrals for radiological examinations, confidence building in patient and patient safety in radiotherapy.

A review of recent advances in optical fibre sensors for in vivo dosimetry during radiotherapy.

This article presents an overview of the recent developments and requirements in radiotherapy dosimetry, with particular emphasis on the development of optical fibre dosemeters for radiotherapy applications, focusing particularly on in vivo applications. Optical fibres offer considerable advantages over conventional techniques for radiotherapy dosimetry, owing to their small size, immunity to electromagnetic interferences, and suitability for remote monitoring and multiplexing. The small dimensions of optical fibre-based dosemeters, together with being lightweight and flexible, mean that they are minimally invasive and thus particularly suited to in vivo dosimetry. This means that the sensor can be placed directly inside a patient, for example, for brachytherapy treatments, the optical fibres could be placed in the tumour itself or into nearby critical tissues requiring monitoring, via the same applicators or needles used for the treatment delivery thereby providing real-time dosimetric information. The article outlines the principal sensor design systems along with some of the main strengths and weaknesses associated with the development of these techniques. The successful demonstration of these sensors in a range of different clinical environments is also presented.

Future development of biologically relevant dosimetry.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.