Production and regulatory issues for theranostics.

Theranostics has become a major area of innovation and progress in cancer care over the last decade. In view of the introduction of approved therapeutics in neuroendocrine tumours and prostate cancer in the last 10 years, the ability to provide access to these treatments has emerged as a key factor in ensuring global benefits from this cancer therapy approach. In this Series paper we explore the issues that affect access to and availability of theranostic radiopharmaceuticals, including supply and regulatory issues that might affect the availability of theranostic treatments for patients with cancer.

Recurrent medical imaging exposures for the care of patients: one way forward.

Medical imaging is both valuable and essential in the care of patients. Much of this imaging depends on ionizing radiation with attendant responsibilities for judicious use when performing an examination. This responsibility applies in settings of both individual as well as multiple (recurrent) imaging with associated repeated radiation exposures. In addressing the roles and responsibilities of the medical communities in the paradigm of recurrent imaging, both the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have issued position statements, each affirmed by other organizations. The apparent difference in focus and approach has resulted in a lack of clarity and continued debate. Aiming towards a coherent approach in dealing with radiation exposure in recurrent imaging, the IAEA convened a panel of experts, the purpose of which was to identify common ground and reconcile divergent perspectives. The effort has led to clarifying recommendations for radiation exposure aspects of recurrent imaging, including the relevance of patient agency and the provider-patient covenant in clinical decision-making. CLINICAL RELEVANCE STATEMENT: An increasing awareness, generating some lack of clarity and divergence in perspectives, with patients receiving relatively high radiation doses (e.g., ≥ 100 mSv) from recurrent imaging warrants a multi-stakeholder accord for the benefit of patients, providers, and the imaging community. KEY POINTS: • Recurrent medical imaging can result in an accumulation of exposures which exceeds 100 milli Sieverts. • Professional organizations have different perspectives on roles and responsibilities for recurrent imaging. • An expert panel reconciles differing perspectives for addressing radiation exposure from recurrent medical imaging.

Guardians of precision: advancing radiation protection, safety, and quality systems in nuclear medicine.

BACKGROUND: In the rapidly evolving field of nuclear medicine, the paramount importance of radiation protection, safety, and quality systems cannot be overstated. This document provides a comprehensive analysis of the intricate regulatory frameworks and guidelines, meticulously crafted and updated by national and international regulatory bodies to ensure the utmost safety and efficiency in the practice of nuclear medicine. METHODS: We explore the dynamic nature of these regulations, emphasizing their adaptability in accommodating technological advancements and the integration of nuclear medicine with other medical and scientific disciplines. RESULTS: Audits, both internal and external, are spotlighted for their pivotal role in assessing and ensuring compliance with established standards, promoting a culture of continuous improvement and excellence. We delve into the significant contributions of entities like the International Atomic Energy Agency (IAEA) and relevant professional societies in offering universally applicable guidelines that amalgamate the latest in scientific research, ethical considerations, and practical applicability. CONCLUSIONS: The document underscores the essence of international collaborations in pooling expertise, resources, and insights, fostering a global community of practice where knowledge and innovations are shared. Readers will gain an in-depth understanding of the practical applications, challenges, and opportunities presented by these regulatory frameworks and audit processes. The ultimate goal is to inspire and inform ongoing efforts to enhance safety, quality, and effectiveness in nuclear medicine globally.

Safety in radiation oncology (SAFRON): Learning about incident causes and safety barriers in external beam radiotherapy.

PURPOSE: Safety in Radiation Oncology (SAFRON) is a reporting and learning system on radiotherapy and radionuclide therapy incidents and near misses. The primary aim of this paper is to examine whether any discernible patterns exist in the causes of reported incidents and safety barriers within the SAFRON system concerning external beam radiotherapy. METHODS AND MATERIALS: This study focuses on external beam radiotherapy incidents, reviewing 1685 reports since the inception of SAFRON until December 2021. Reports that did not identify causes of incidents and safety barriers were excluded from the final study population. RESULTS: Simple two-dimensional radiotherapy or electron beam therapy were represented by 97 reports, three-dimensional conformal radiotherapy by 39 reports, modulated arc therapy by 12 reports, intensity modulated radiation therapy by 11 reports, stereotactic radiosurgery by 4 reports, and radiotherapy with protons or other particles by 1 report, while for 92 of them, no information on treatment method had been provided. Most of the reported incidents were minor incidents and were discovered by the radiation therapist. Inadequate direction/information in staff communication was the most frequently reported cause of incident, and regular independent chart check was the most common safety barrier. CONCLUSIONS: The results indicate that the majority of incidents were reported by radiation therapists, and the majority of these incidents were classified as minor. Communication problems and failure to follow standards/procedures/practices were the most frequent causes of incidents. Furthermore, regular independent chart checking was the most frequently identified safety barrier.

Communication of radiation risk from imaging studies: an IAEA-coordinated international survey.

The purpose of this IAEA-coordinated international study was to understand aspects related to the communication of radiation risk from imaging studies, such as how often imaging department personnel and referring physicians are asked about radiation risks in diagnostic imaging, who asks about these risks, how often professionals are able to provide satisfactory answers using qualitative metrics and how often quantitative risk estimates are needed. A web-based questionnaire with ten questions was completed by 386 healthcare professionals from 63 countries from all four continents, including clinicians/referring physicians (42.5%), radiologists or nuclear medicine physicians (26.7%), medical physicists (23.1%), radiographers/radiological technologists (6.2%) and others (1.6%). The results indicate that radiation risk-related questions are largely asked by patients (73.1%) and parents of child patients (38.6%), and 78% of the professionals believe they are able to answer those questions using qualitative metrics such as very small/minimal, small, medium rather than number of cancers likely occurring. The vast majority, with over three times higher frequency, indicated the purpose of knowing previous radiological exams as 'both clinical information and radiation exposure history' rather than 'only clinical information'. Nearly two-thirds of the clinicians/referring physicians indicated that knowing the radiation exposure history of the patient will affect their decision-making for the next exam, as against only about one-fifth who said 'no, it will not affect their decision-making'. The same question, when addressed to radiologists, resulted in a slightly larger fraction of about three-quarters who said 'yes', as opposed to a smaller fraction of about 12% who said 'no, it will not affect their decision-making'. Mapping the present situation of communication of benefits and risks for patients is important and may be the basis of further analysis, regular monitoring and possibly a target for clinical audits. Further studies focused on specific professional groups might help in obtaining á deeper understanding of the need for practical communication tools.

Strengthening radiation protection education and training of health professionals: conclusions from an IAEA meeting.

In March 2021 the International Atomic Energy Agency (IAEA) organised an online Technical Meeting on Developing Effective Methods for Radiation Protection Education and Training of Health Professionals with attendance of 230 participants representing 66 Member States and 24 international organizations, professional bodies and safety alliances. By means of a pre-meeting survey, presentations by experts, topical panel discussions and post-meeting feedback to the meeting summary, the meeting identified strengths, common weaknesses and possible solutions and actions for improving radiation protection education and training of health professionals. Available guidelines and resources for radiation protection training were also reviewed. The meeting discussion resulted in a strong consensus for the need of: (a) international guidance on education and training in radiation protection and safety for health professionals, (b) an international description of minimum standards of initial and ongoing competence and qualification in radiation protection for relevant professional groups, considering the available recommendations at international and regional levels. The proposed actions include provisions for train-the-trainer credentialing and facility training accreditation, balance betwee the online and face-to-face training, improved on-the job training, as well as improved inclusion in training programmes of aspects related to application of new technologies, ethical aspects, development of communication skills, and use of software tools for improving justification and optimisation. The need for making the ongoing training practical, applicable, and useful to the trainee was highlighted. The international consultation initiated by the IAEA was appreciated as a good approach to understand and promote coordination and collaboration at all levels, for best results in education and training in radiation protection of health professionals. Implementing such a holistic approach to education and training in radiation protection would contribute towards qualification and competence of health professionals needed to ensure application of high standards for quality and safety in medical uses of ionizing radiation.

Radiation protection perspective to recurrent medical imaging: what is known and what more is needed?

This review summarises the current knowledge about recurrent radiological imaging and associated cumulative doses to patients. The recent conservative estimates are for around 0.9 million patients globally who cumulate radiation doses above 100 mSv, where evidence exists for cancer risk elevation. Around one in five is estimated to be under the age of 50. Recurrent imaging is used for managing various health conditions and chronic diseases such as malignancies, trauma, end-stage kidney disease, cardiovascular diseases, Crohn's disease, urolithiasis, cystic pulmonary disease. More studies are needed from different parts of the world to understand the magnitude and appropriateness. The analysis identified areas of future work to improve radiation protection of individuals who are submitted to frequent imaging. These include access to dose saving imaging technologies; improved imaging strategies and appropriateness process; specific optimisation tailored to the clinical condition and patient habitus; wider utilisation of the automatic exposure monitoring systems with an integrated option for individual exposure tracking in standardised patient-specific risk metrics; improved training and communication. The integration of the clinical and exposure history data will support improved knowledge about radiation risks from low doses and individual radiosensitivity. The radiation protection framework will need to respond to the challenge of recurrent imaging and high individual doses. The radiation protection perspective complements the clinical perspective, and the risk to benefit analysis must account holistically for all incidental and long-term benefits and risks for patients, their clinical history and specific needs. This is a step toward the patient-centric health care.

How often does it happen? A review of unintended, unnecessary and unavoidable high-dose radiation exposures.

High-dose radiation exposures of humans occur every year around the world, and may lead to harmful tissue reactions. This review aims to look at the available information sources that can help answering the question of how often these events occur yearly on a global scale. In the absence of comprehensive databases of global occurrence, publications on radiation accidents in all uses of radiation and on rates of high-dose events in different medical uses of radiation have been reviewed. Most high-dose radiation exposures seem to occur in the medical uses of radiation, reflecting the high number of medical exposures performed. In therapeutic medical uses, radiation doses are purposely often given at levels known to cause deterministic effects, and there is a very narrow range in which the medical practitioner can operate without causing severe unacceptable outcomes. In interventional medical uses, there are scenarios in which the radiation dose given to a patient may reach or exceed a threshold for skin effects, where this radiation dose may be unavoidable, considering all benefits and risks as well as benefits and risks of any alternative procedures. Regardless of if the delivered dose is unintended, unnecessary or unavoidable, there are estimates published of the rates of high-dose events and of radiation-induced tissue injuries occurring in medical uses. If this information is extrapolated to a global scenario, noting the inherent limitations in doing so, it does not seem unreasonable to expect that the global number of radiation-induced injuries every year may be in the order of hundreds, likely mainly arising from medical uses of radiation, and in particular from interventional fluoroscopy procedures and external beam radiotherapy procedures. These procedures are so frequently employed throughout the world that even a very small rate of radiation-induced injuries becomes a substantial number when scaled up to a global level.

Medical imaging and nuclear medicine: a Lancet Oncology Commission.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.

Variations in CT Utilization, Protocols, and Radiation Doses in COVID-19 Pneumonia: Results from 28 Countries in the IAEA Study.

Background There is lack of guidance on specific CT protocols for imaging patients with coronavirus disease 2019 (COVID-19) pneumonia. Purpose To assess international variations in CT utilization, protocols, and radiation doses in patients with COVID-19 pneumonia. Materials and Methods In this retrospective data collection study, the International Atomic Energy Agency coordinated a survey between May and July 2020 regarding CT utilization, protocols, and radiation doses from 62 health care sites in 34 countries across five continents for CT examinations performed in patients with COVID-19 pneumonia. The questionnaire obtained information on local prevalence, method of diagnosis, most frequent imaging, indications for CT, and specific policies on use of CT in COVID-19 pneumonia. Collected data included general information (patient age, weight, clinical indication), CT equipment (CT make and model, year of installation, number of detector rows), scan protocols (body region, scan phases, tube current and potential), and radiation dose descriptors (CT dose index and dose length product). Descriptive statistics and generalized estimating equations were performed. Results Data from 782 patients (median age, 59 years [interquartile range, 15 years]) from 54 health care sites in 28 countries were evaluated. Less than one-half of the health care sites used CT for initial diagnosis of COVID-19 pneumonia and three-fourths used CT for assessing disease severity. CT dose index varied based on CT vendors (7-11 mGy; P < .001), number of detector rows (8-9 mGy; P < .001), year of CT installation (7-10 mGy; P = .006), and reconstruction techniques (7-10 mGy; P = .03). Multiphase chest CT examinations performed at 20% of sites (11 of 54) were associated with higher dose length product compared with single-phase chest CT examinations performed in 80% of sites (43 of 54) (P = .008). Conclusion CT use, scan protocols, and radiation doses in patients with coronavirus disease 2019 pneumonia showed wide variation across health care sites within the same and between different countries. Many patients were imaged multiple times and/or with multiphase CT scan protocols. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee in this issue.

Chest CT practice and protocols for COVID-19 from radiation dose management perspective.

The global pandemic of coronavirus disease 2019 (COVID-19) has upended the world with over 6.6 million infections and over 391,000 deaths worldwide. Reverse-transcription polymerase chain reaction (RT-PCR) assay is the preferred method of diagnosis of COVID-19 infection. Yet, chest CT is often used in patients with known or suspected COVID-19 due to regional preferences, lack of availability of PCR assays, and false-negative PCR assays, as well as for monitoring of disease progression, complications, and treatment response. The International Atomic Energy Agency (IAEA) organized a webinar to discuss CT practice and protocol optimization from a radiation protection perspective on April 9, 2020, and surveyed participants from five continents. We review important aspects of CT in COVID-19 infection from the justification of its use to specific scan protocols for optimizing radiation dose and diagnostic information.Key Points• Chest CT provides useful information in patients with moderate to severe COVID-19 pneumonia.• When indicated, chest CT in most patients with COVID-19 pneumonia must be performed with non-contrast, low-dose protocol.• Although chest CT has high sensitivity for diagnosis of COVID-19 pneumonia, CT findings are non-specific and overlap with other viral infections including influenza and H1N1.

Clinical imaging guidelines part 4: challenges in identifying, engaging and collaborating with stakeholders.

The effective development and use of clinical imaging guidelines requires an understanding of who the stakeholders are, what their interests in the process are, and what roles they should play. If the appropriate stakeholders are not engaged in the right roles, it is unlikely that clinical imaging guidelines will be successfully developed, relied on, and actually used. Some stakeholders are obvious: for the development of clinical imaging guidelines, both imagers and those who request examinations, such as general practitioners, internists, and medical specialists, must be involved. To gain acceptance, other relevant groups are stakeholders, including medical societies, other health care professionals, insurers, health IT experts and vendors, and patients. The role of stakeholders must be dictated by their specific interest. For some, involvement in the creation of guidelines is the right role. For others, such as regulators or insurers, reviews or invitations to comment are required, and for others, such as medical educators, it is probably sufficient to provide information and create awareness. Only through a careful consideration of who the stakeholders are and what are their interests are the successful development, acceptance, and use of clinical imaging guidelines likely to occur. Future efforts must focus on collaboration, particularly among groups that create clinical imaging guidelines and those that can support their use, and on regulatory roles and mandates.

Monitoring of clinical imaging guidelines part 3: norms, standards, and regulations.

It is known that the use of imaging in clinical situations is not always optimal, leading to suboptimal health care and potential radiation risk. There may be overuse of imaging, underuse, or use of the wrong modality. The use of clinical imaging guidelines is likely to improve the use of imaging, but roadblocks exist. Some of these relate to regulatory oversight and mandates. There is wide variation by country and region in the regulatory setting, ranging from actual absence of regulatory authorities to mandated availability of clinical imaging guidelines in the European Community. Collaborative efforts to ensure that clinical imaging guidelines are at least available is a good starting point. Regulatory oversight and support are necessary to ensure the use of clinical imaging guidelines. Regulations should address 3 areas: availability, clinical utilization, and adherence to and revision of guidelines. The use of both internal and external audits, with the aim of both use of and adherence to guidelines and quality improvement, is the best tool for enhancing use. The major challenges that need to be addressed, collaboratively, to ensure the dissemination and use of clinical imaging guidelines are the development of regulations, of regulatory structures that can be effectively deployed, and of benchmarks for adherence and for utility.

Clinical imaging guidelines part 2: Risks, benefits, barriers, and solutions.

A recent international meeting was convened by two United Nations bodies to focus on international collaboration on clinical appropriateness/referral guidelines for use in medical imaging. This paper, the second of 4 from this technical meeting, addresses barriers to the successful development/deployment of clinical imaging guidelines and means of overcoming them. It reflects the discussions of the attendees, and the issues identified are treated under 7 headings: ■ Practical Strategy for Development and Deployment of Guidelines; ■ Governance Arrangements and Concerns with Deployment of Guidelines; ■ Finance, Sustainability, Reimbursement, and Related Issues; ■ Identifying Benefits and Radiation Risks from Radiological Examinations; ■ Information Given to Patients and the Public, and Consent Issues; ■ Special Concerns Related to Pregnancy; and ■ The Research Agenda. Examples of topics identified include the observation that guideline development is a global task and there is no case for continuing it as the project of the few professional organizations that have been brave enough to make the long-term commitment required. Advocacy for guidelines should include the expectations that they will facilitate: (1) better health care delivery; (2) lower cost of that delivery; with (3) reduced radiation dose and associated health risks. Radiation protection issues should not be isolated; rather, they should be integrated with the overall health care picture. The type of dose/radiation risk information to be provided with guidelines should include the uncertainty involved and advice on application of the precautionary principle with patients. This principle may be taken as an extension of the well-established medical principle of "first do no harm."

Clinical imaging guidelines part 1: a proposal for uniform methodology.

Inappropriate imaging can lead to unnecessary medical radiologic exposures and cost and may not answer the clinical question. Imaging referral guidelines inform the justification of radiologic procedures and facilitate the choice of the best test first, but their acceptance by referrers, use, and value may be limited by shortcomings in the methodology of development. Focusing on common, essential elements of methodology will help guideline developers. In 2012 and 2013, the International Atomic Energy Agency hosted Technical Meetings on Radiation Protection of Patients Through the Development of Appropriateness Criteria in Diagnostic Imaging. Participants identified and agreed on issues concerning development of imaging referral guidelines. Items based on the Appraisal of Guidelines for Research and Evaluation II instrument were amended with additional items including development and consensus group composition. Consensus was sought on 28 items, 18 of which were agreed should be uniform, and 10 should allow for regional differences. Further work is required to encourage, provide, and identify higher quality evidence and to agree on a grading system for recommendations. Many key areas are common to guideline developers globally, opening the way for international collaboration to help demystify, simplify, and justify.

Addressing patient safety through the use of 'criteria of acceptability' for medical radiation equipment.

Patient safety should be considered in the use of ionising radiation equipment in medicine. The International Atomic Energy Agency (IAEA) establishes standards of safety and provides for the application of these standards, also in the area of medical use of radiation. Equipment acceptability, as it relates to radiation in medicine, is the need to satisfy the requirements or standards prior to the use of the device in patient imaging or treatment. Through IAEA activities in establishing and developing Safety Standards, Safety Reports and recommendations to regulatory authorities and end-users, it encourages the adoption of acceptability criteria that are relevant to the medical equipment and its use.

Safety in radiation oncology: the role of international initiatives by the International Atomic Energy Agency.

The International Atomic Energy Agency (IAEA) has a wide range of initiatives that address the issue of safety. Quality assurance initiatives and comprehensive audits of radiotherapy services, such as the Quality Assurance Team for Radiation Oncology, are available through the IAEA. Furthermore, the experience of the IAEA in thermoluminescence dosimetric audits has been transferred to the national level in various countries and has contributed to improvements in the quality and safety of radiotherapy. The IAEA is also involved in the development of a safety reporting and analysis system (Safety in Radiation Oncology). In addition, IAEA publications describe and analyze factors contributing to safety-related incidents around the world. The lack of sufficient trained, qualified staff members is addressed through IAEA programs. Initiatives include national, regional, and interregional technical cooperation projects, educational workshops, and fellowship training for radiation oncology professionals, as well as technical assistance in developing and initiating local radiation therapy, safety education, and training programs. The agency is also active in developing staffing guidelines and encourages advanced planning at a national level, aided by information collection systems such as the Directory of Radiotherapy Centers and technical cooperation project personnel planning, to prevent shortages of staff. The IAEA also promotes the safe procurement of equipment for radiation therapy centers within a comprehensive technical cooperation program that includes clinical, medical physics, and radiation safety aspects and review of local infrastructure (room layout, shielding, utilities, and radiation safety), the availability of qualified staff members (radiation oncologists, medical physicists, and radiation technologists and therapists), as well as relevant imaging, treatment planning, dosimetry, and quality control items. The IAEA has taken the lead in developing a comprehensive program that addresses all of these areas of concern and is actively contributing to the national and international efforts to make radiation therapy safer in all settings, including resource-limited settings.

International action plan on the radiation protection of patients.

Realising that the major part of radiation protection efforts had been directed for over half a century at radiation protection of workers, and that there are major issues in relation to medical exposure, which contributes to over 95 % of the dose to the global population from man-made sources, with increasing individual patient doses in diagnostic examinations, unnecessary or inappropriate examinations and continued accidents in radiotherapy, the International Atomic Energy Agency established an International Action Plan (IAP) in 2002 in cooperation with international organisations and professional bodies. The achievements of the IAP, which include harmonised training material, guidance documents, a number of publications, a website on radiation protection of patients (http://rpop.iaea.org) and a series of actions in Member States that have shown positive impacts on patient protection, are summarised in this paper.

Radiation Oncology Safety Information System (ROSIS)--profiles of participants and the first 1074 incident reports.

BACKGROUND AND PURPOSE: The Radiation Oncology Safety Information System (ROSIS) was established in 2001. The aim of ROSIS is to collate and share information on incidents and near-incidents in radiotherapy, and to learn from these incidents in the context of departmental infrastructure and procedures. MATERIALS AND METHODS: A voluntary web-based cross-organisational and international reporting and learning system was developed (cf. the www.rosis.info website). Data is collected via online Department Description and Incident Report Forms. A total of 101 departments, and 1074 incident reports are reviewed. RESULTS: The ROSIS departments represent about 150,000 patients, 343 megavoltage (MV) units, and 114 brachytherapy units. On average, there are 437 patients per MV unit, 281 per radiation oncologist, 387 per physicist and 353 per radiation therapy technologist (RT/RTT). Only 14 departments have a completely networked system of electronic data transfer, while 10 departments have no electronic data transfer. On average seven quality assurance (QA) or quality control (QC) methods are used at each department. A total of 1074 ROSIS reports are analysed; 97.7% relate to external beam radiation treatment and 50% resulted in incorrect irradiation. Many incidents arise during pre-treatment but are not detected until later in the treatment process. Where an incident is not detected prior to treatment, an average of 22% of the prescribed treatment fractions were delivered incorrectly. The most commonly reported detection methods were "found at time of patient treatment" and during "chart-check". CONCLUSION: While the majority of the incidents that reported to this international cross-organisational reporting system are of minor dosimetric consequence, they affect on average more than 20% of the patient's treatment fractions. Nonetheless, defence-in-depth is apparent in departments registered with ROSIS. This indicates a need for further evaluation of the effectiveness of quality controls.