The role of SSDL in quality assurance in radiotherapy

This paper describes the role of the Polish Secondary Standard Dosimetry Laboratory (SSDL) in quality assurance in radiotherapy by means of providing calibration of ionisation chambers, TLD postal dosimetry audits and end-to-end audits for radiation therapy. A historical review of the methods and results are presented. The influence of the SSDL in Warsaw on radiation protection of patients in Poland is discussed. The International Atomic Energy Agency together with World Health Organisation (IAEA/WHO), through its network of SSDLs around the world, propagates newly developed methods for calibration and auditing. Suitable high quality equipment was provided by the IAEA, as well as special materials and technical support to the SSDL in Warsaw. The activity of the SSDL and the services provided for Polish radiotherapy centres have resulted in a reduction of discrepancies between planned doses and doses delivered to patients. The newly tested IAEA methods of end-to-end on-site dosimetry audits allow for monitoring and improving the quality of IMRT in Poland. The traceability of standards used for the calibration of therapy level dosimeters from Polish radiotherapy centres is assured by the IAEA dosimetry laboratory. The consistency of methods performed in the Polish SSDL with the ISO:17025 norm is supervised by the Polish Centre for Accreditation – a member of International Laboratory Accreditation Cooperation (ILAC), for calibration and testing. Due to the rapid technological development of radiotherapy, special attention has to be paid to newly developed methods for dosimetry auditing and institutions which provide services for assuring radiation safety of patients.     

Dosimetry quality control based on percent depth dose rate variation for checking beam quality in radiotherapy

Recently, the quality management inside a radiotherapy department has been crucial to treat cancer efficiently. Thus, many international bodies recommend multiple methods to check in periodically the dosimetry quality beyond the depth of 10 cm as the beam quality index. However, they evade checking out the beam dosimetry quality on both the build-up dose and the electronic equilibrium regions. The objective of this study is to cover the overall variation of the percent depth dose (PDD) by including all sub-regions in the procedure evaluation of the beam quality.In this work, we have studied and examined the dosimetry quality by considering the whole PDD variation. The PDD rate is therefore introduced to determine accurately the quality as an overall notion in external beam radiotherapy according to the field size and photon beam energy. We have presented the reasons and methods to introduce particles contamination, such as electrons and low photon energy in this new approach. The latter enables us to figure the dosimetry quality by extending the International Atomic Energy Agency (IAEA) procedure at any field size less than 25 × 25 cm² under the current conditions without being limited to 10 × 10 cm² on the exponential decay region.     

The IAEA Radiotracer Biodistribution Template – A community resource for supporting the standardization and reporting of radionuclide pre-dosimetry data

Radionuclide absorbed-dose dosimetry is an active area of development and has the potential to positively impact molecular radiotherapies. At present, many of the operations required to perform dosimetry calculations are unstandardized and unestablished. While the current methodology allows reasonable dosimetry estimates to be derived and published, it can be difficult to understand, and reproduce, each others’ work. To help alleviate this we have identified the collection of biodistribution information as a key step in all internal dosimetry calculations, and present a template that can be used to standardize its documentation and reporting.A generalized biodistribution template entitled the IAEA Radiotracer Biodistribution Template (IAEA RaBiT) has been built and distributed for users performing biodistribution measurements in the community. The template enables robust recording of dosimetry-relevant information through standardization of details and their format. It has been designed to be simple and easy to use, and establish a structured recording of a common reference point in dosimetry operations – biodistribution data documentation. Improved documentation procedures may benefit organization of in house data, or be used to disseminate details throughout the community – for example to supplement dosimetry related publications. The standard format information may also enable the creation of new dosimetry related tools and protocols and support robust population databases.As dosimetry in nuclear medicine becomes more routinely applied in clinical applications, we need to develop the infrastructure for robustly handling large amounts of these data. Our IAEA RaBiT can be used as a standard format structure for data collection, organization, and dissemination.     

Biodosimetry and assessment of radiation dose

Aim

When investigating radiation accidents, it is very important to determine the exposition dose to the individuals. In the case of exposures over 1 Gy, clinicians may expect deterministic effects arising the following weeks and months, in these cases dose estimation will help physicians in the planning of therapy. Nevertheless, for doses below 1 Gy, biodosimetry data are important due to the risk of developing late stochastic effects. Finally, some accidental overexposures are lack of physical measurements and the only way of quantifying dose is by biological dosimetry.

Background

The analysis of chromosomal aberrations by different techniques is the most developed method of quantifying dose to individuals exposed to ionising radiations.^1,2 Furthermore, the analysis of dicentric chromosomes observed in metaphases from peripheral lymphocytes is the routine technique used in case of acute exposures to assess radiation doses.

Materials and methods

Solid stain of chromosomes is used to determine dicentric yields for dose estimation. Fluorescence in situ hybridization (FISH) for translocations analysis is used when delayed sampling or suspected chronically irradiation dose assessment. Recommendations in technical considerations are based mainly in the IAEA Technical Report No. 405.²

Results

Experience in biological dosimetry at Gregorio Marañón General Hospital is described, including own calibration curves used for dose estimation, background studies and real cases of overexposition.

Conclusion

Dose assessment by biological dosimeters requires a large previous standardization work and a continuous update. Individual dose assessment involves high qualification professionals and its long time consuming, therefore requires specific Centres. For large mass casualties cooperation among specialized Institutions is needed.     

The International Atomic Energy Agency action plan on radiation protection of patients and staff in interventional procedures: Achieving change in practice

IntroductionThe International Atomic Energy Agency (IAEA) organized the 3rd international conference on radiation protection (RP) of patients in December 2017. This paper presents the conclusions on the interventional procedures (IP) session.Material and methodsThe IAEA conference was conducted as a series of plenary sessions followed by various thematic sessions. “Radiation protection of patients and staff in interventional procedures” session keynote speakers presented information on: 1) Risk management of skin injuries, 2) Occupational radiation risks and 3) RP for paediatric patients. Then, a summary of the session-related papers was presented by a rapporteur, followed by an open question-and-answer discussion.ResultsSixty-seven percent (67%) of papers came from Europe. Forty-four percent (44%) were patient studies, 44% were occupational and 12% were combined studies. Occupational studies were mostly on eye lens dosimetry. The rest were on scattered radiation measurements and dose tracking. The majority of patient studies related to patient exposure with only one study on paediatric patients. Automatic patient dose reporting is considered as a first step for dose optimization. Despite efforts, paediatric IP radiation dose data are still scarce. The keynote speakers outlined recent achievements but also challenges in the field. Forecasting technology, task-specific targeted education from educators familiar with the clinical situation, more accurate estimation of lens doses and improved identification of high-risk professional groups are some of the areas they focused on.ConclusionsManufacturers play an important role in making patients safer. Low dose technologies are still expensive and manufacturers should make these affordable in less resourced countries. Automatic patient dose reporting and real-time skin dose map are important for dose optimization. Clinical audit and better QA processes together with more studies on the impact of lens opacities in clinical practice and on paediatric patients are needed.     

The evolution and impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in the Latin American region

Since 1993, the IAEA supported the establishment or the consolidation of seven tissue banks in the region. As a direct or indirect consequence of the implementation of the IAEA program, more than 53 tissue banks are now operating in the participating countries. The fast development of tissue banks in the Latin America region under the ARCAL Agreement and with the financial and technical support of the IAEA program made it necessary to train new tissue bank operators and medical personnel. In general, 90 tissue bank operators and medical personnel were trained in the training centre of Buenos Aires. Another six tissue bank operators and medical personnel were trained in the International Training Centre of Singapore. The main impact of the IAEA program in the region was the following: the establishment or consolidation of fifty-three tissue banks in nine countries in the region; the implementation of five national projects, allocating $1,006,737 dollars for this purpose and of one regional project allocating $284,741 dollars for this purpose; the use of the IAEA Standards, the IAEA Code of Practice and the IAEA Public Awareness Strategies in several tissue banks in the region; the application of quality control and quality assurances manuals in all of the participating countries.     

Health-related monitoring and assessment of airborne particulate matter

Since 1992, the International Atomic Energy Agency (IAEA) has been promoting studies of air pollution using a standard design of air sampler that provides separation on filters into two size fractions with cutoffs of 2.5 and 10 Μm (approximately). These are the size ranges presently considered to have the most important health consequences. Such filter samples are highly amenable to analysis using nuclear and related techniques. After reviewing some of the health effects of airborne particulate matter and current air quality standards and guidelines, this article provides an overview of current and recent IAEA programs in this area, which involve collaborative activities with participants in more than 40 countries.     

A New Model of Biodosimetry to Integrate Low and High Doses

Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation.     

The cytogenetic dosimetry of recent accidental overexposure.

When accidental exposure to ionizing radiations is suspected, optimal choice of a treatment strategy requires, in addition to information about the clinical signs and physical dosimetry, a determination by biological parameters of the dose received. The scoring of unstable chromosomal aberrations in peripheral blood lymphocytes is the current reference method. Preparation of these samples depends on the goal sought--an exact assessment of several irradiations or rapid triage in the case of a large-scale accident. Moreover, some adaptation may be necessary if the irradiation is either heterogenous or not recent. Despite the robustness and adaptability of this procedure, conventional cytogenetics remains a tedious and time-consuming technique, and it requires specialized staff. Scoring micronuclei in binucleated lymphocytes may be an easier, simpler altemative to a dicentric assay. This paper, which is based on the experience acquired by the IPSN in recent years in expert assessment of suspected radiations, has as its goal to provide a succinct technical guideline of these different approaches, as they are adapted to suspected recent irradiation and triage.     

The evolution and impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Asia and the Pacific region

The Asia and the Pacific region was within the IAEA program on radiation and tissue banking, the most active region. Most of the tissue banks in the Asia and the Pacific region were developed during the late 1980s and 1990s. The initial number of tissue banks established or supported by the IAEA program in the framework of the RCA Agreement for Asia and the Pacific region was 18. At the end of 2006, the number of tissue banks participating, in one way or another in the IAEA program was 59. Since the beginning of the implementation of the IAEA program in Asia and the Pacific region 63,537 amnion and 44,282 bone allografts were produced and 57,683 amnion and 36,388 bone allografts were used. The main impact of the IAEA program in the region was the following: the establishment or consolidation of at least 59 tissue banks in 15 countries in the region (the IAEA supported directly 16 of these banks); the improvement on the quality and safety of tissues procured and produced in the region reaching international standards; the implementation of eight national projects, two regional projects and two interregional projects; the elaboration of International Standards, a Code of Practice and a Public Awareness Strategies and, the application of quality control and quality assurances programs in all participating tissue banks.     

A Feasibility Study of Fricke Dosimetry as an Absorbed Dose to Water Standard for 192Ir HDR Sources

High dose rate brachytherapy (HDR) using ¹⁹²Ir sources is well accepted as an important treatment option and thus requires an accurate dosimetry standard. However, a dosimetry standard for the direct measurement of the absolute dose to water for this particular source type is currently not available. An improved standard for the absorbed dose to water based on Fricke dosimetry of HDR ¹⁹²Ir brachytherapy sources is presented in this study. The main goal of this paper is to demonstrate the potential usefulness of the Fricke dosimetry technique for the standardization of the quantity absorbed dose to water for ¹⁹²Ir sources. A molded, double-walled, spherical vessel for water containing the Fricke solution was constructed based on the Fricke system. The authors measured the absorbed dose to water and compared it with the doses calculated using the AAPM TG-43 report. The overall combined uncertainty associated with the measurements using Fricke dosimetry was 1.4% for k = 1, which is better than the uncertainties reported in previous studies. These results are promising; hence, the use of Fricke dosimetry to measure the absorbed dose to water as a standard for HDR ¹⁹²Ir may be possible in the future.     

A modified system for analyzing ionizing radiation-induced chromosome abnormalities

The analysis of dicentric chromosomes in human peripheral blood lymphocytes (PBLs) by Giemsa staining is the most established method for biological dosimetry. However, this method requires a well-trained person because of the difficulty in detecting aberrations rapidly and accurately. Here, we applied a fluorescence in situ hybridization (FISH) technique, using telomere and centromere peptide nucleic acid (PNA) probes, to solve the problem of biological dosimetry in radiation emergency medicine. A comparison by a well-trained observer found that FISH analysis of PBLs for the dose estimation was more accurate than the conventional Giemsa analysis, especially in samples irradiated at high doses. These results show that FISH analysis with centromeric/telomeric PNA probes could become the standard method for biological dosimetry in radiation emergency medicine.     

WHO informal consultation on regulatory evaluation of therapeutic biological medicinal products held at WHO Headquarters, Geneva, 19-20 April 2007.

This report reflects the discussion and conclusions of an informal consultation held on 19-20 April 2007 at the World Health Organization concerning the regulatory evaluation of therapeutic biological medicinal products. The objectives of this meeting were to discuss the current status of so-called "similar" biological medicinal products (biosimilars) and to review regulatory pathways and challenges in evaluating the quality, safety and efficacy of these products. Biosimilars are products that are subject to licensing with a reduced data package due to a proven 'similarity' to the licensed reference product. The meeting was attended by experts in biotherapeutics from regulatory agencies, industry and academia representing 16 countries worldwide. Dr. Elwyn Griffiths (Canada) acted as Chairman and Dr. James Robertson (UK) was the Rapporteur. The meeting strongly focused on the usage of biosimilars and the current regulatory situation in many different countries. The application of International Nonproprietary Names (INN) to biosimilars, their potential immunogenicity, and WHO international standards and reference materials were also discussed, alongside presentations from the innovator and generic manufacturing industries. The consultation recognized the importance of the terminology as well as a definition of biosimilars for future considerations of these products. However, achieving a global consensus on the terminology for these new challenging products was not attempted at the Consultation, and it was decided that a future WHO working group should act on this issue as a next step. For purposes of this meeting report only, the term 'biosimilars' is temporarily used to refer to this category of products. It became clear that biotherapeutics authorized on the basis of a reduced data package are available and being used in some countries, with more appearing on the market. The existence of divergent approaches to the regulatory oversight of biosimilars in different countries revealed a need for defining regulatory expectations for these products at the global level. While many countries are following the guideline developed within the EU for quality aspects, discrepancies remain regarding the non-clinical and clinical studies of these products. The Consultation recommended that the WHO should develop a guideline in this area in order to provide a framework for the development of regulatory pathways for these products worldwide. For this purpose, agreement on the scope, definition and terminology of these products was deemed necessary. The interchangeability and substitution of products were also flagged as areas in need of harmonization. A WHO working group should be established to develop a guideline that would promote global consensus on the regulation of biosimilars, assist in their registration and enhance the availability of safe and effective biosimilar products worldwide.     

Developing and implementing a multi-modality imaging optimization study in paediatric radiology: Experience and recommendations from an IAEA coordinated research project

Optimization of imaging examinations is a key requirement of both the International and European Basic Safety Standards, and the focus of much international activity. Although methodologies are well established in principle, there continues to be a variety of practical issues both in collecting and interpreting dose and image quality data and in making successful interventions to optimize exposures.A Coordinated Research Project, involving institutes from ten different countries, was established by the IAEA to assess the efficacy of recommended optimization methodologies in the field of paediatric radiology and to derive practical guidance on their implementation. The steps followed in this process were identification of the imaging process to be investigated (abdomen and chest x-rays, micturating cysto-urethrograms, and brain & thorax CT scans); collection of dose and image quality data; evaluation and comparison of the data between institutes and to standards; identification and implementation of interventions for optimization; and re-evaluation of dose and image quality parameters.The project succeeded both in achieving effective interventions for optimization of specific imaging tasks in individual institutes and in identifying key issues with potential to handicap this process. The main area in which problems were encountered was in the collation of reliable dose and image quality data. The reasons for this were explored and a series of recommendations have been made, summarized into ‘ten practical tips’ for optimization to assist institutes, particularly those in the early stages of addressing optimization issues.     

Three-dimensional quality assurance of IMRT prostate plans using gel dosimetry

Intensity modulated radiotherapy (IMRT) is one of the most modern radiation therapy treatment techniques. Although IMRT can deliver high and complex conformational doses to the tumor volume, its implementation requires rigorous quality assurance (QA) procedures that include a dosimetric pre-treatment verification of individual patient planning. This verification usually involves measuring a small volume of absolute dose with an ionization chamber and checking bi-dimensional fluency with an array of detectors. The planning technique has tri-dimensional characteristics, but no tridimensional dosimetry has been established in the clinical routine. One strategy to perform three-dimensional dosimetry is to use polymeric gels associated with magnetic resonance imaging to evaluate dose distribution. Here, we have compared the results of conventional QA procedures involving one- and two-dimensional dosimetry to the results of three-dimensional dosimetry conducted with MAGIC-f gel in 10 cases of prostate cancer IMRT planning. More specifically, we used the gamma index (3%/3 mm) to compare the results of three-dimensional dosimetry to the expected dose distributions obtained with the treatment planning system. Except for one IMRT treatment plan, the gel dosimetry results agreed with the conventional quality control and provided an overview of dose distribution in the target volume.     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Asia and the Pacific and the Latin American regions

The technical assistance program of the International Atomic Energy Agency (IAEA) for its member states in the framework of the implementation of its program on radiation and tissue banking focuses on ensuring the availability of quality radiation-sterilised tissue grafts. The IAEA also helps its member states to develop quality control capabilities in order to ensure the safe use of the processed tissues in certain medical treatments. The majority of developing countries does not have such capacity, and must import expensive sterilised tissues from developed countries. The IAEA’s core contribution to its program on radiation and tissue banking in Asia and the Pacific and the Latin American regions is a technology for sterilisation by gamma radiation and a training program for tissue bank operators and medical personnel. The Agency develops capabilities for radiation sterilisation of tissue grafts, both for reducing the pre-processing bacterial load, and as a terminal sterilisation process. Sterilising tissue grafts offers a clear advantage in terms of safety. Moreover, compared to alternative sterilisation methods, radiation sterilisation is considered particularly safe in relation to environmental concerns, and the deposition of harmful residuals in the tissue, which occurs for example in the use of chemical such as ethylene oxide gas. Radiation sterilisation, thus, has become the method of choice for an increasing number of tissue banks. Radiation sterilisation of tissue grafts is a critical component in the chain connecting donors to recipients of high quality tissue grafts. Due to this fact, the IAEA has evolved as the only organisation in the UN System with expertise related to tissue banking.     

The importance of the selection of the audiences and the organization of media events within public awareness strategies for tissue banks

The main purpose of the International Atomic Energy Agency (IAEA) Public Awareness Strategies for Tissue Banks is to provide guidance on organizing and running awareness campaigns, in order to consolidate tissue banking activities. Within the IAEA Public Awareness Strategies for Tissue Banks, there are two important topics, which need to be singled out due to their importance for a successful public and professional awareness campaign. These are the selection of the audiences and the organization of media events within a Communication Strategy. The experience in the field of tissue banking in several countries has shown that interaction between the public, the professional health care staff, the media and the tissue bank personnel is essential if the activities of the banks are to be successful. It must be emphasized however, that any public and professional awareness strategy will not be successful, unless it is considered as part of an integrated system that is adopted by the concerned Government.     

WHO technical workshop on stability of reference materials for biological medicines and in vitro diagnostics, Geneva, Switzerland, 28–29 November 2005

In November 2005, the World Health Organization convened an informal technical workshop on the stability of reference materials for biological medicines and in vitro diagnostics. The meeting was attended by experts from WHO collaborating centres in the area of biological standardization, national control laboratories, industries and other relevant organizations. The consultation group discussed current practices and approaches to predicting and monitoring the stability of biological reference materials. The group agreed to the need for establishing a working group (i) to continue dialogue on potential issues encompassing the principles, strategies and practicality for assuring the stability of WHO international reference standards for biological medicines and in vitro diagnostics and (ii) to develop more detailed guidance for assessment of the stability of WHO international biological reference materials.     

Clinical laboratory implementation of cytogenomic microarrays

Examination of the whole genome for copy number alterations by microarray is now routinely done in many laboratories. The field of cytogenetics has evolved to adapt this technology, and the current phase of transition has resulted in the need for standardization in methodologies and interpretation of data. This review will outline some of the changes addressed in the field over the last several years and briefly discuss some of the trends in data processing, analysis and interpretation.     

A critical survey of fish measurements in populations of the southern Urals

A critical survey of all published measurements made so far aimed at retrospective biological dosimetry using fluorescence in situ hybridisation (FISH) techniques on some workers at the Mayak reprocessing plant and on members of the Techa River cohort is given. Each individual has a recorded dose derived from personal monitoring measurements, usually external gamma-rays for Mayak workers or from reconstruction techniques, usually internally derived for the Techa River cohort. From the person's age, which affects the control level, and the stated dose, an expected number of translocations is calculated for each individual and comparisons made to the observed numbers of translocations. From this, an assessment of how well FISH studies can help to validate existing estimates of dose is made. This varies from study to study. Good agreement is generally obtained for the Techa River cohort and lower doses of the Mayak cohort. Rather poorer agreement applies to the more highly exposed Mayak workers. Some of the discrepancy could be because the FISH painting technique was new and was applied to populations before a proper investigation on how to use it for retrospective biological dosimetry had taken place. In addition, too few cells were generally scored per individual so that statistical uncertainties were large.