The use of dose quantities in radiological protection: ICRP publication 147 Ann ICRP 50(1) 2021.

The International Commission on Radiological Protection has recently published a report (ICRP Publication 147;Ann. ICRP50, 2021) on the use of dose quantities in radiological protection, under the same authorship as this Memorandum. Here, we present a brief summary of the main elements of the report. ICRP Publication 147 consolidates and clarifies the explanations provided in the 2007 ICRP Recommendations (Publication 103) but reaches conclusions that go beyond those presented in Publication 103. Further guidance is provided on the scientific basis for the control of radiation risks using dose quantities in occupational, public and medical applications. It is emphasised that best estimates of risk to individuals will use organ/tissue absorbed doses, appropriate relative biological effectiveness factors and dose-risk models for specific health effects. However, bearing in mind uncertainties including those associated with risk projection to low doses or low dose rates, it is concluded that in the context of radiological protection, effective dose may be considered as an approximate indicator of possible risk of stochastic health effects following low-level exposure to ionising radiation. In this respect, it should also be recognised that lifetime cancer risks vary with age at exposure, sex and population group. The ICRP report also concludes that equivalent dose is not needed as a protection quantity. Dose limits for the avoidance of tissue reactions for the skin, hands and feet, and lens of the eye will be more appropriately set in terms of absorbed dose rather than equivalent dose.

[Palliative care of patients receiving opioid substitution therapy]. / Palliativversorgung von Patienten in Opioidsubstitutionsbehandlung.

Patients with opioid use disorder survive longer and reach higher ages due to harm reduction and maintenance programs. Therefor and because of concomitant comorbidities there is an increased incidence of life-limiting diseases. Thus, increasing numbers of patients with opioid use disorder or in maintenance programs will require palliative care. However, both inpatient and outpatient service providers are uncertain about providing palliative care for these patients. Home-care teams and inpatient hospices have been known to refuse admission for patients with opioid use disorder. Providing medical care to patients receiving substitution therapy can be challenging because maintenance programs require strict compliance with their rules and regulations; however, an individualized approach with knowledge of basic legal requirements enables good palliative care. In this manner, it is possible to ensure healthcare for these aging patients.

Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D+ repl; n=28) or T-cell-depleted (D+ depl; n=16) graft from a CMV-seropositive donor were screened for CMV-specific T-cell immunity. Eight D+ depl recipients received adoptive T-cell therapy from their stem cell donor. CMV epitope-specific T cells were well supported and became detectable in all treated patients. Complete and partial virological response rates were 62.5% and 25%, respectively. Owing to longsome third-party donor (TPD) identification, only 8 of the 57 CMV patients transplanted from CMV-seronegative donors (D-) received antigen-specific T cells from partially human leukocyte antigen (HLA)-matched TPDs. In all but one, TPD-derived CMV-specific T cells remained undetectable. In summary, adoptive transfer correlated with functional virus-specific T-cell reconstitution in D+ depl patients. Suboptimal HLA match may counteract expansion of TPD-derived virus-specific T cells in D- patients.

Fifteen symposia on microdosimetry: implications for modern particle-beam cancer radiotherapy.

The objective of microdosimetry was, and still is, to identify physical descriptions of the initial physical processes of ionising radiation interacting with biological matter which correlate with observed radiobiological effects with a view to improve the understanding of radiobiological mechanisms and effects. The introduction of therapy with particles starting with fast neutrons followed by negative pions, protons and light ions necessitated the application of biological weighting factors for absorbed dose in order to account for differences of the relative biological effectiveness (RBE). Dedicated radiobiological experiments in therapy beams with mammalian cells and with laboratory animals provided sets of RBE values which are used to evaluate empirical 'clinical RBE values'. The combination of such experiments with microdosimetric measurements in identical conditions offered the possibility to establish semi-empirical relationships between microdosimetric parameters and results of RBE studies.

Doses from radiation exposure.

Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effective dose. In preparation for the calculation of new dose coefficients, Committee 2 and its task groups have provided updated nuclear decay data (ICRP Publication 107) and adult reference computational phantoms (ICRP Publication 110). New dose coefficients for external exposures of workers are complete (ICRP Publication 116), and work is in progress on a series of reports on internal dose coefficients to workers from inhaled and ingested radionuclides. Reference phantoms for children will also be provided and used in the calculation of dose coefficients for public exposures. Committee 2 also has task groups on exposures to radiation in space and on the use of effective dose.

Effective dose: a radiation protection quantity.

Modern radiation protection is based on the principles of justification, limitation, and optimisation. Assessment of radiation risks for individuals or groups of individuals is, however, not a primary objective of radiological protection. The implementation of the principles of limitation and optimisation requires an appropriate quantification of radiation exposure. The International Commission on Radiological Protection (ICRP) has introduced effective dose as the principal radiological protection quantity to be used for setting and controlling dose limits for stochastic effects in the regulatory context, and for the practical implementation of the optimisation principle. Effective dose is the tissue weighted sum of radiation weighted organ and tissue doses of a reference person from exposure to external irradiations and internal emitters. The specific normalised values of tissue weighting factors are defined by ICRP for individual tissues, and used as an approximate age- and sex-averaged representation of the relative contribution of each tissue to the radiation detriment of stochastic effects from whole-body low-linear energy transfer irradiations. The rounded values of tissue and radiation weighting factors are chosen by ICRP on the basis of available scientific data from radiation epidemiology and radiation biology, and they are therefore subject to adjustment as new scientific information becomes available. Effective dose is a single, risk-related dosimetric quantity, used prospectively for planning and optimisation purposes, and retrospectively for demonstrating compliance with dose limits and constraints. In practical radiation protection, it has proven to be extremely useful.

Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies.

When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatment prescription. However, the clinical outcome does not only depend on absorbed dose but also on a number of other factors such as dose per fraction, overall treatment time and radiation quality radiation biology effectiveness (RBE). Therefore, weighting factors have to be applied when different types of treatments are to be compared or to be combined. This had led to the concept of 'isoeffective absorbed dose', introduced by ICRU and International Atomic Energy Agency (IAEA). The isoeffective dose D(IsoE) is the dose of a treatment carried out under reference conditions producing the same clinical effects on the target volume as those of the actual treatment. It is the product of the total absorbed dose (in gray) used and a weighting factor W(IsoE) (dimensionless): D(IsoE)=D×W(IsoE). In fractionated photon-beam therapy, the dose per fraction and the overall treatment time (in days) are the two main parameters that the radiation oncologist has the freedom to adjust. The weighting factor for an alteration of the dose per fraction is commonly evaluated using the linear-quadratic (α/ß) model. For therapy with protons and heavier ions, radiation quality has to be taken into account. A 'generic proton RBE' of 1.1 for clinical applications is recommended in a joint ICRU-IAEA Report [ICRU (International Commission on Radiation Units and Measurements) and IAEA (International Atomic Energy Agency). Prescribing, recording and reporting proton-beam therapy. ICRU Report 78, jointly with the IAEA, JICRU, 7(2) Oxford University Press (2007)]. For heavier ions (e.g. carbon ions), the situation is more complex as the RBE values vary markedly with particle type, energy and depth in tissue.

Reversible foetal cerebral ventriculomegaly and cardiomyopathy under chemotherapy for maternal AML.

BACKGROUND: Leukaemia in pregnancy is a rare complication demanding a multidisciplinary approach and careful management to handle potential complications and cope with ethical dilemmas. PATIENT AND METHODS: We report on a patient with acute myeloid leukaemia (AML) relapse in 22 weeks of gestation who received chemotherapy with cytarabine and mitoxantrone, as well as fludarabine, cytarabine, idarubicin, and gemtuzumabozogamicin. We describe findings on regular ultrasound examinations and successful management of complications. RESULTS: The foetus developed signs of anthracycline-induced cardiomyopathy, transient cerebral ventriculomegaly, anaemia, and intrauterine growth restriction. The child was delivered by Caesarean section at 33 + 1 weeks of gestation. The newborn showed no congenital malformations. CONCLUSION: This case report confirms that chemotherapy for treatment of AML can be applied in the second trimester of pregnancy under close and careful maternal and foetal monitoring.

Response of neutron detectors to high-energy mixed radiation fields.

Radiation protection around CERN's high-energy accelerators represents a major challenge due to the presence of complex, mixed radiation fields. Behind thick shielding neutrons dominate and their energy ranges from fractions of eV to about 1 GeV. In this work the response of various portable detectors sensitive to neutrons was studied at CERN's High-Energy Reference Field Facility (CERF). The measurements were carried out with conventional rem counters, which usually cover neutron energies up to 20 MeV, the Thermo WENDI-2, which is specified to measure neutrons up to several GeV, and a tissue-equivalent proportional counter. The experimentally determined neutron dose equivalent results were compared with Monte Carlo (MC) simulations. Based on these studies field calibration factors can be determined, which result in a more reliable estimate of H*(10) in an unknown, but presumably similar high-energy field around an accelerator than a calibration factor determined in a radiation field of a reference neutron source.

Curvas ângulo-tempo das articulações dos eqüinos marchadores / Joint angle-time curves of Brazilian gaited horses

Gráficos com demonstração das curvas ângulo-tempo das articulações dos membros dos eqüinos foram avaliados por meio da análise de imagens digitalizadas tomadas de 10 cavalos e 13 éguas da raça Mangalarga Marchador. Foram utilizados marcadores reflexivos adesivos colocados em 19 pontos articulares dos eqüinos, procedendo-se à filmagem com freqüência de 250 quadros por segundo e utilizando-se o aplicativo Simi-motion 3D 6.0 para digitalização e análise das imagens. A utilização dos marcadores reflexivos adesivos constituiu boa metodologia para análise dos movimentos dos segmentos ósseos dos eqüinos. Os resultados observados indicam haver, durante a locomoção dos eqüinos marchadores brasileiros, comportamento similar das articulações quando comparados com eqüinos de sela europeus, apresentando mesmo padrão das curvas de ângulo-tempo e não havendo grandes diferenças entre os pontos máximos de flexão e extensão.

Images of 10 horses and 13 mares of Mangalarga Marchador breed were taken and digitalized to analyze the joint angle-time curves. Reflexives and adhesives markers were glued on 19 articulations points of the hindlimbs and forelimbs of the horses. The images were taken at 250 frames per second and the digitalization and analysis were made using a Simi-motion 3D 6.0 software. The results demonstrated that the methodology using reflexives and adhesives markers was efficient to make analyses of the bone segment movements of the horses. This study concluded that the Brazilian gaited horses have a similar angle-joint curve as the European warmblood horses and there are no great differences of the maximum extension and flexion points.

The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Lasting remission following multimodal treatment in a patient with metastatic breast cancer.

We report on a lasting remission from multimodal treatment in a patient with hepatic metastasized breast cancer. After surgical removal of a singular hepatic metastasis, the patient underwent leukapheresis of peripheral blood mononuclear cell (PBMCs). For induction chemotherapy, the patient received 2 cycles of epirubicin and paclitaxel (ET). After 1 cycle of epirubicin and ifosfamide (EI), peripheral blood stem cells were harvested. After a final cycle of ET, the patient underwent high-dose chemotherapy (HDCT; thiotepa 600 mg/m/melphalan 180 mg/m) and autologous stem cell transplantation. Once reconstitution was achieved, PBMCs were reinfused followed by i.v. application of a trifunctional antibody (TrAb) with specificities anti-EpCAMxanti-CD3. TrAbs are able to simultaneously bind tumor cells, T cells, and additionally FcgammaR type I and III+accessory cells via their Fc region. Side-effects during treatment were hematotoxicity, mucositis and gastrointestinal toxicity. TrAb treatment resulted in intermittent fever, chills, elevated liver enzymes, systemic inflammatory response syndrome and pulmonary leakage. With a follow-up period of more than 8 years the patient is still in remission (96+months). This case suggests the feasibility and efficacy of combining surgery, standard and HDCT, and subsequent immunotherapy in metastatic breast cancer. Further investigation of this approach is indicated in a subgroup of patients with oligometastatic breast cancer.

Combined treatment of metastatic breast cancer (MBC) by high-dose chemotherapy (HDCT) and bispecific antibodies: a pilot study.

UNLABELLED: This pilot study analyzed the efficacy and toxicity of high-dose chemotherapy (HDCT), autologous stem-cell transplantation (ASCT) and subsequent immunotherapy with T-cell reinfusion and trifunctional antibodies (trAbs) in chemotherapy-sensitive patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: After leukapheresis and cryopreservation of T-cells, patients received 2 cycles of induction chemotherapy ET (epirubicin/paclitaxel) and 1 cycle of El (epirubicin/ifosfamide), followed by G-CSF and stem-cell harvest. After a final cycle of ET, responders (CR/PR) underwent HDCT (thiotepa 600 mg/m2/melphalan 140-180 mg/m2) and ASCT. Once reconstitution was achieved, T-cells were reinfused, followed by application of trifunctional antibodies with specificities anti-EpCAM X anti-CD3 and anti-Her2/neu X anti-CD3. RESULTS: Thirty-three patients were recruited into the study and 19, who had responded to initial chemotherapy, underwent HDCT and ASCT (4 CR, 15 PR, OR = 57.6%; 95% CI: 40-75%). Two early deaths were observed (1 toxic, 1 early progression). T-cell reinfusion and trAbs were given to 17 patients. TrAbs treatment resulted in intermittent fever, chills and elevated liver enzymes, which were seen in all patients. The median overall survival was 27.7 months (range: 5.9-82.6+). Patients who received 3 trAbs doses showed a trend towards an improved overall survival (47.2 vs. 22.4 months, p = 0.08 log rank). CONCLUSION: This pilot study has shown the feasibility of combining HDCT with immunotherapy in MBC. Further investigation of this approach is indicated.

The ICRU (International Commission on Radiation Units and Measurements): its contribution to dosimetry in diagnostic and interventional radiology.

The ICRU (International Commission on Radiation Units and Measurements was created to develop a coherent system of quantities and units, universally accepted in all fields where ionizing radiation is used. Although the accuracy of dose or kerma may be low for most radiological applications, the quantity which is measured must be clearly specified. Radiological dosimetry instruments are generally calibrated free-in-air in terms of air kerma. However, to estimate the probability of harm at low dose, the mean absorbed dose for organs is used. In contrast, at high doses, the likelihood of harm is related to the absorbed dose at the site receiving the highest dose. Therefore, to assess the risk of deterministic and stochastic effects, a detailed knowledge of absorbed dose distribution, organ doses, patient age and gender is required. For interventional radiology, where the avoidance of deterministic effects becomes important, dose conversion coefficients are generally not yet developed.

Dose quantities in radiation protection and their limitations.

For more than 50 years the quantity absorbed dose has been the basic physical quantity in the medical applications of ionising radiation as well as radiological protection against harm from ionising radiation. In radiotherapy relatively high doses are applied (to a part of the human body) within a short period and the absorbed dose is mainly correlated with deterministic effects such as cell killing and tissue damage. In contrast, in radiological protection one is dealing with low doses and low dose rates and long-term stochastic effects in tissue such as cancer induction. The dose quantity (absorbed dose) is considered to be correlated with the probability of cancer incidence and thus risk induced by exposure. ICRP has developed specific dosimetric quantities for radiological protection that allow the extent of exposure to ionising radiation from whole and partial body external radiation as well as from intakes of radionuclides to be taken into account by one quantity. Moreover, radiological protection quantities are designed to provide a correlation with risk of radiation induced cancer. In addition, operational dose quantities have been defined for use in measurements of external radiation exposure and practical applications. The paper describes the concept and considerations underlying the actual system of dose quantities, and discusses the advantage as well as the limitations of applicability of such a system. For example, absorbed dose is a non-stochastic quantity defined at any point in matter. All dose quantities in use are based on an averaging procedure. Stochastic effects and microscopic biological and energy deposition structures are not considered in the definition. Absorbed dose is correlated to the initial very short phase of the radiation interaction with tissue while the radiation induced biological reactions of the tissue may last for minutes or hours or even longer. There are many parameters other than absorbed dose that influence the process of cancer induction, which may influence the consideration of cells and/or tissues at risk which are most important for radiological protection.