Patient-specific biokinetics and hybrid 2D/3D approach integration in OEDIPE software: Application to radioiodine therapy.

BACKGROUND: The progression of targeted radionuclide therapy requires the development of dosimetry software accounting for patient-specific biokinetics. New functionalities were thus developed in the OEDIPE software, to deal with multiple 3D images or multiple planar images and a SPECT image. MATERIEL & METHOD: Methods were implemented to recover patient biokinetics in volumes of interest. If several 3D SPECT images are available, they are registered to a reference CT scan. When several planar images and a single SPECT are available, the planar images are registered to the SPECT and counts of the planar images converted to activity. To validate these developments, six SPECT/CT and planar images of a Jaszczak phantom containing I-131 were acquired at different dates. Cumulated activity was estimated in each sphere using the SPECT/CT images only or the planar series associated to one SPECT/CT. Biokinetics and doses in lesions and in the lungs of a patient treated with I-131 for differentiated thyroid cancer were then estimated using four planar images and a SPECT/CT scan. Whole-body retention data were used to compare the biokinetics obtained from the planar and SPECT data. RESULTS: Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient compared well with those derived from whole-body retention data. CONCLUSION: The implemented features allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling patient-specific dosimetry without the need for external software to estimate the cumulated activities in different VOIs.

EURADOS work on internal dosimetry.

European Radiation Dosimetry Group (EURADOS) Working Group 7 is a network on internal dosimetry that brings together researchers from more than 60 institutions in 21 countries. The work of the group is organised into task groups that focus on different aspects, such as development and implementation of biokinetic models (e.g. for diethylenetriamine penta-acetic acid decorporation therapy), individual monitoring and the dose assessment process, Monte Carlo simulations for internal dosimetry, uncertainties in internal dosimetry, and internal microdosimetry. Several intercomparison exercises and training courses have been organised. The IDEAS guidelines, which describe - based on the International Commission on Radiological Protection's (ICRP) biokinetic models and dose coefficients - a structured approach to the assessment of internal doses from monitoring data, are maintained and updated by the group. In addition, Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides have been elaborated on behalf of the European Commission, DG-ENER (TECHREC Project, 2014-2016, coordinated by EURADOS). Quality assurance of the ICRP biokinetic models by calculation of retention and excretion functions for different scenarios has been performed and feedback was provided to ICRP. An uncertainty study of the recent caesium biokinetic model quantified the overall uncertainties, and identified the sensitive parameters of the model. A report with guidance on the application of ICRP biokinetic models and dose coefficients is being drafted at present. These and other examples of the group's activities, which complement the work of ICRP, are presented.

LESSONS LEARNED FROM THE EURADOS SURVEY ON INDIVIDUAL MONITORING DATA AND INTERNAL DOSE ASSESSMENTS OF FOREIGNERS EXPOSED IN JAPAN FOLLOWING THE FUKUSHIMA DAIICHI NPP ACCIDENT.

European Radiation Dosimetry Group e.V. (EURADOS) survey on individual monitoring data and dose assessment has been carried out for 550 foreigners returning home after being exposed in Japan to intakes of radionuclides (mainly (131)I, (132)I, (132)Te, (134)Cs and (137)Cs) as a consequence of the Fukushima Daiichi NPP accident. In vivo and in vitro measurements were performed in their respective countries at an early stage after that accident. Intakes of radionuclides were detected in 208 persons from Europe and Canada, but the committed effective dose E(50) was below the annual dose limit for the public (<1 mSv) in all the cases. Lessons learned from this EURADOS survey are presented here regarding not only internal dosimetry issues, but also the management of the emergency situation, the perception of the risk of health effects due to radiation and the communication with exposed persons who showed anxiety and lack of trust in monitoring data and dose assessments.

Uncertainty induced by chest wall thickness assessment methods on lung activity estimation for plutonium and americium: a large population-based study.

In vivo lung counting aims at assessing the retained activity in the lungs. The calibration factor relating the measured counts to the worker's specific retained lung activity can be obtained by several means and strongly depends on the chest wall thickness. Here we compare, for 374 male nuclear workers, the activity assessed with a reference protocol, where the material equivalent chest wall thickness is known from ultrasound measurements, with two other protocols. The counting system is an array of four germanium detectors.It is found that non site-specific equations for the assessment of the chest wall thickness induce large biases in the assessment of activity. For plutonium isotopes or (241)Am the proportion of workers for whom the retained activity is within ± 10% of the reference one is smaller than 10%.The use of site-specific equations raises this proportion to 20% and 58% for plutonium and (241)Am, respectively.Finally, for the studied population, when site-specific equations are used for the chest wall thickness, the standard uncertainties for the lung activity are 42% and 12.5%, for plutonium and (241)Am, respectively. Due to the relatively large size of the studied population, these values are a relatively robust estimate of the uncertainties due to the assessment of the chest wall thickness for the current practice at this site.

Clinical results of an EPID-based in-vivo dosimetry method for pelvic cancers treated by intensity-modulated radiation therapy.

The purpose of our work was to investigate the feasibility of using an EPID-based in-vivo dosimetry method initially designed for conformal fields on pelvic dynamic IMRT fields. The method enables a point dose delivered to the patient to be calculated from the transit signal acquired with an electronic portal imaging device (EPID). After defining a set of correction factors allowing EPID pixel values to be converted into absolute doses, several tests on homogeneous water-equivalent phantoms were performed to estimate the validity of the method in reference conditions. The effects of different treatment parameters, such as delivered dose, field size dependence and patient thickness were also studied. The model was first evaluated on a group of 53 patients treated by 3D conformal radiotherapy (3DCRT) and then on 92 patients treated by IMRT, both for pelvic cancers. For each measurement, the dose was reconstructed at the isocenter (DREC) and compared with the dose calculated by our treatment planning system (DTPS). Excellent agreement was found between DREC and DTPS for both techniques. For 3DCRT treatments, the mean deviation between DREC and DTPS for the 211 in-vivo dose verifications was equal to -1.0  ±  2.2% (1SD). Concerning IMRT treatments, the averaged deviation for the 418 fields verified was equal to -0.3 ± 2.6% (1SD) proving that the method is able to reconstruct a dose for dynamic IMRT pelvic fields. Based on these results, tolerance criteria and action levels were established before its implementation in clinical routine.

Adjuvant radiotherapy in the management of axillary node negative invasive breast cancer: a qualitative systematic review.

PURPOSE: To actualize and to detail guidelines used in technical radiotherapy and indications for innovative radiation technologies in early axillary node negative breast cancer (BC). METHODS: Dosimetric and treatment planning studies, phase II and III trials, systematic reviews and retrospective studies were all searched (Medline(®) database). Their quality and clinical relevance were also checked against validated checklists. A level of evidence was associated for each result. RESULTS: A total of 75 references were included. Adjuvant BC radiotherapy (50Gy/25 fractions/5 weeks followed by a tumor boost of 16Gy/8 fractions) is still the standard of care. Overall treatment time could be shortened for patients who present with low local relapse risk BC by using either hypofractionated whole breast irradiation; or accelerated partial breast irradiation. BC IMRT is not used in current practice. CONCLUSION: Our group aimed to provide guidelines for technical and clinical applications of innovative BC radiation technologies.

EURADOS coordinated action on research, quality assurance and training of internal dose assessments.

EURADOS working group on 'Internal Dosimetry (WG7)' represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

Analysis of a computational problem involving complex voxel geometries.

This communication briefly summarises the results obtained from the 'International comparison on MC modeling for in vivo measurement of Americium in a knee phantom' organised within the EU Coordination Action CONRAD (Coordinated Network for Radiation Dosimetry) as a joint initiative of EURADOS working groups 6 (computational dosimetry) and 7 (internal dosimetry). Monte Carlo simulations using the knee voxel phantom proved to be a viable approach to provide the calibration factor needed for in vivo measurements.

Validation of a personalized dosimetric evaluation tool (Oedipe) for targeted radiotherapy based on the Monte Carlo MCNPX code.

Dosimetric studies are necessary for all patients treated with targeted radiotherapy. In order to attain the precision required, we have developed Oedipe, a dosimetric tool based on the MCNPX Monte Carlo code. The anatomy of each patient is considered in the form of a voxel-based geometry created using computed tomography (CT) images or magnetic resonance imaging (MRI). Oedipe enables dosimetry studies to be carried out at the voxel scale. Validation of the results obtained by comparison with existing methods is complex because there are multiple sources of variation: calculation methods (different Monte Carlo codes, point kernel), patient representations (model or specific) and geometry definitions (mathematical or voxel-based). In this paper, we validate Oedipe by taking each of these parameters into account independently. Monte Carlo methodology requires long calculation times, particularly in the case of voxel-based geometries, and this is one of the limits of personalized dosimetric methods. However, our results show that the use of voxel-based geometry as opposed to a mathematically defined geometry decreases the calculation time two-fold, due to an optimization of the MCNPX2.5e code. It is therefore possible to envisage the use of Oedipe for personalized dosimetry in the clinical context of targeted radiotherapy.

Current developments at IRSN on computational tools dedicated to assessing doses for both internal and external exposure.

The paper presents the OEDIPE (French acronym that stands for tool for personalised internal dose assessment) and SESAME (for simulation of external source accident with medical images) computational tools, dedicated to internal and external dose assessment, respectively, and currently being developed at the Institute for Radiological Protection and Nuclear Safety. The originality of OEDIPE and SESAME, by using voxel phantoms in association with Monte Carlo codes, lies in their ability to construct personalised voxel phantoms from medical images and automatically generate the Monte Carlo input file and visualise the expected results. OEDIPE simulates in vivo measurements to improve their calibration, and calculates the dose distribution taking both internal contamination and internal radiotherapy cases into account. SESAME enables radiological overexposure doses to be reconstructed, as also victim, source and accident environment modelling. The paper presents the principles on which these tools function and an overview of specificities and results linked to their fields of application.

Dosimetric comparison of Monte Carlo codes (EGS4, MCNP, MCNPX) considering external and internal exposures of the Zubal phantom to electron and photon sources.

This paper aims at comparing dosimetric assessments performed with three Monte Carlo codes: EGS4, MCNP4c2 and MCNPX2.5e, using a realistic voxel phantom, namely the Zubal phantom, in two configurations of exposure. The first one deals with an external irradiation corresponding to the example of a radiological accident. The results are obtained using the EGS4 and the MCNP4c2 codes and expressed in terms of the mean absorbed dose (in Gy per source particle) for brain, lungs, liver and spleen. The second one deals with an internal exposure corresponding to the treatment of a medullary thyroid cancer by 131I-labelled radiopharmaceutical. The results are obtained by EGS4 and MCNPX2.5e and compared in terms of S-values (expressed in mGy per kBq and per hour) for liver, kidney, whole body and thyroid. The results of these two studies are presented and differences between the codes are analysed and discussed.

Análise de radioelementos, a níveis de traços, utilizando espectrometria de massa de íons secundários / Analysis of radioelements by levels of traits using mass spectrometry of secundary ions

A espectrometria de massa de íons secundários (SIMS) permite a detecção rápida de elementos estáveis ou radioativos, bem como o cálculo de seu percentual isotópico. Ademais, essa técnica possibilita a localização de radioisótipos, à níveis de traços, em amostras biológicas. Neste trabalho procurou-se estudar a utilização dessa metodologia na detecção de urânio natural à baixa concentração. Estudos sobre a preparação de amostras e limites de detecção foram também realizados.

Irreversible changes in rat erythrocyte Na+ transport systems with progesterone and estradiol administration.

In order to test whether alterations in Na+ transport systems occurring in women when the hormonal status is disturbed such as in pregnancy, under contraceptive or estradiol therapy are a direct result of hormonal action on these transport systems, Na+,K+-pump Na+,K+ outward cotransport and passive Na+ permeability were measured in erythrocytes of ovariectomized rats receiving estradiol or progesterone. No significant changes in Na+,K+-pump were observed in either conditions. Conversely, progesterone was found to decrease Na+, K+-cotransport and estradiol to increase this system, whereas both steroids increased passive Na+ permeability.

In vivo modulation of outward Na+, K+ cotransport by oestradiol and progesterone in rat red cells.

Outward Na+, K+-cotransport was 50% higher in female than in male rat red cells (50%). Ovariectomy induced a marked decrease in the activity of this system. Oestradiol increased and progesterone decreased Na+, K+-cotransport in ovariectomized rats.

[Primary tumors of the renal pelvis and ureter: value of postoperative external radiotherapy (author's transl)]. / Tumeurs primitives urétéro-pyelo-calicielles. Etude comparative de l'importance thérapeutique de la radiothérapie loco-régionale.

Twenty-four observations of primary malignant tumors of the renal pelvis and ureter derived from epithelial cells were included in this study. Thirteen patients were treated by radiotherapy and surgery. In eleven patients, surgical excision was the only treatment. Although patients were not randomized there was no significant difference between the two groups concerning the following parameters: age distribution, sex ratio, stage of disease, histological grade, surgical procedure. The morbidity related to external radiotherapy (megavoltage technique, delivering 45 grays in 5 weeks) was low: only one patient developed retroperitoneal fibrosis. No patient was lost to follow-up. Local recurrence occurred in 54.5% of the patients treated by surgery alone, against 15.5% after combined radio-surgical therapy. The overall three-year survival rate was 35% without any significant difference between the two groups. The authors advocate postoperative high-voltage radiotherapy for non-disseminated carcinoma of the renal pelvis and ureter.