First Latin American and Caribbean interlaboratory comparison exercise for SSDLs on reference irradiation capabilities in personal dose equivalent.

A comparison exercise of Latin American and Caribbean Secondary Standards Dosimetry Laboratories (SSDLs) was jointly organized by the International Atomic Energy Agency (IAEA) and the Ionizing Radiation Metrology Laboratory at the Federal University of Pernambuco (LMRI-DEN/UFPE). This exercise was organized during an IAEA regional meeting on the review and update of calibration capabilities in Latin America, held in Recife, during the period from 23 to 27 April 2018 under the technical cooperation project ME-RLA 9085-170572. Fifteen participating SSDLs were required to irradiate optically stimulated personal dosimeters in terms of the personal dose equivalent Hp(10) in137Cs radiation quality. In addition, the IAEA Dosimetry Laboratory in Seibersdorf, Austria, and the National Physical Laboratory in Teddington, Middlesex, UK participated in this exercise as reference institutes. Each participant received 10 dosimeters that were hand-carried directly to the SSDL. Two nominal dose values of 2 mSv and 4 mSv were selected for this exercise. The participants irradiated the dosimeters using the setup and the procedures which are normally used in their standard laboratory for Hp(10) dosimeter irradiations. The dosimeters were evaluated as they were received by the coordinating laboratory, using a single BeOSL Reader. The results show that, except for one laboratory, the differences between the dosimeter reading and the assigned values were within 10%; this is consistent with the expanded uncertainty. The results indicate that most of the participant laboratories have a good capability to irradiate personal dosimeters in the quantity Hp(10).

Scan factors and practices associated with radiation doses for chest CT: current Brazilian scenario.

The main purpose of this study was to compare the parameters of computed tomography (CT) and the corresponding patient doses undergoing chest CT scan examinations in different regions of Brazil, providing the current scenario of how these procedures are being carried out in the country as well as the patient dose distribution. Thirty institutions, across 17 states and the Federal District, participated in the survey. The evaluation included 30 multislice CTs of seven different models, manufactured by General Electric (GE) Healthcare. For each institution, data from 10 adult chest CT examinations, performed without contrast, were collected remotely. The analysis of the results showed a significant difference of the CTDIvolvalues, ranging from 1.1 mGy to 46.6 mGy in seven institutions. The mean value of CTDIvolwas higher than values found in the literature and the UK Reference Levels. It was also observed that, regardless of the region of the country, for the same CT model, different scanning parameters were used, which resulted in CTDIvolup to 5 times higher in some institutions. Repetitions of CT acquisitions and scouts with radiation field dimensions larger than the region of interest were found in 25% of chest examinations, resulting in higher absorbed doses. The results of this work show a mapping of the chest CT procedures, which enables the establishment of strategic plans for the country. In addition, each institution will be able to implement an appropriate optimization program and establish institutional reference levels.

Evaluation of a 3D printed OSL eye lens dosimeter for photon dosimetry.

This work demonstrates the use of high-resolution 3D printing to fine-tune the low energy dependence of an eye lens dosimeter holder associated to a BeO OSL detector element (ezClip). Five geometries of the denominated iBe dosimeter were developed, three with a variation in the thickness of the wall in front of the sensitive element that tailor the response at low radiation energies; and three with variations of width and curvature in order to vary the angular response of the dosimeter badges. Additive manufacturing was accomplished using stereolithography which gave a high degree of accuracy and precision. The optimised dosimeter badges showed a low energy and angular dependence, within -20% to +20% in the energy range of 24 keV to 662 keV and from 0 to 60° incidence; and within -10% to +10% in the energy range of 24 keV to 164 keV and from 0 to 60° incidence. In contrast to other dosimeters with higher effective atomic numbers, the use of BeO as the sensitive element resulted in a flat energy and angular dependence response at low energies. A significant reduction in the measurement uncertainty in the diagnostic radiology energy range was achieved.

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).

Prostatic artery embolization: radiation exposure to patients and staff.

The aim of this study was to evaluate the radiation doses to patients and staff received from the first cases of prostatic artery embolization (PAE) conducted in a public hospital in Recife, Brazil. Five PAE procedures for 5 men diagnosed with benign prostatic hyperplasia were investigated. In order to characterize patient exposure, dosimetric quantities, such as the air kerma-area product (P KA), the cumulative air kerma at the interventional reference point (Ka,r), the number of images, etc, were registered. To evaluate the possibility for deterministic effects, the peak skin dose (PSD) was measured using radiochromic films. For evaluation of personal dose equivalent and effective dose to the medical staff, thermoluminescent dosemeters (TLD-100) were used. The effective dose was estimated using the double dosimetry alghoritm of von Boetticher. The results showed that the mean patient's PSD per procedure was 2674.2 mGy. With regard to the medical staff, the mean, minimum and maximum effective doses estimated per procedure were: 18 µSv, 12 µSv and 21 µSv respectively. High personal equivalent doses were found for the feet, hands and lens of the eye, due to the use of multiple left anterior oblique projections and the improper use of the suspended lead screen and the lead curtain during procedures.

Estimation of organ doses to patients undergoing hepatic chemoembolization procedures.

The aim of this study is to evaluate organ and tissue absorbed doses to patients undergoing hepatic chemoembolization procedures performed in two hospitals in the city of Recife, Brazil. Forty eight patients undergoing fifty hepatic chemoembolization procedures were investigated. For the 20 cases with PA projection only, organs and tissues dose to KAP conversion coefficients were calculated using the mesh-based anthropometric phantom series FASH and MASH coupled to the EGSnrc Monte Carlo code. Clinical, dosimetric and irradiations parameters were registered for all patients. The maximum organ absorbed doses found were 2.4 Gy, 0.85 Gy, 0.76 Gy and 0.44 Gy for skin, kidneys, adrenals and liver, respectively.

Development of newborn and 1-year-old reference phantoms based on polygon mesh surfaces.

The purpose of this study is the development of paediatric reference phantoms for newborn and 1-year-old infants to be used for the calculation of organ and tissue equivalent doses in radiation protection. The study proposes a method for developing anatomically highly sophisticated paediatric phantoms without using medical images. The newborn and 1-year-old hermaphrodite phantoms presented here were developed using three-dimensional (3D) modelling software applied to anatomical information taken from atlases, textbooks and images provided by the Department of Anatomy of the Federal University of Pernambuco, Brazil. The method uses polygon mesh surfaces to model body contours, the shape of organs as well as their positions and orientations in the human body. Organ and tissue masses agree with corresponding data given by the International Commission on Radiological Protection for newborn and 1-year-old reference children. Bones were segmented into cortical bone, spongiosa, medullary marrow and cartilage to allow for the use of µCT images of trabecular bone for skeletal dosimetry. Anatomical results show 3D images of the phantoms' surfaces, organs and skeletons, as well as tables with organ and tissue masses or skeletal tissue volumes. Dosimetric results present comparisons of organ and tissue absorbed doses or specific absorbed fractions between the newborn and 1-year-old phantoms and corresponding data for other paediatric stylised or voxel phantoms. Most differences were found to be below 10%.

Organ doses and risks of computed tomography examinations in Recife, Brazil.

Computed tomography (CT) examinations have increased significantly in recent years due to technological innovations. In some industrialised countries, CT contributes to the population dose as much as background radiation. In developing countries, the uses and risks of CT have not been well characterised. The purpose of this investigation was to assess potential stochastic and deterministic radiation effects from common CT exams performed in six hospitals of Recife, Pernambuco. Scanning parameters and patient gender and age were collected for a total of 285 patients undergoing CT examinations of the head (90), chest (75), abdomen (60) and abdomen-pelvis (60). The organ doses, which were calculated using the ImPACT dosimetry calculator, varied significantly among institutions. Organs such as the brain, the heart and the eye lenses, which exhibited doses as high as 85, 42 and 100 mGy, respectively, are of concern for the production of cerebrovascular and cardiovascular diseases and cataracts. Effective cancer risks were calculated using Brenner methodology and BEIR-VII risk factors. They range from 1.8 to 110.2 cases per 100000 persons for cancer induction and from 1.5 to 63.0 cases per 100000 for cancer mortality. To reduce doses, a quality assurance programme that includes procedural justification and radiation protection optimisation should be implemented.

Development of 5- and 10-year-old pediatric phantoms based on polygon mesh surfaces.

PURPOSE: The purpose of this study is the development of reference pediatric phantoms for 5- and 10-year-old children to be used for the calculation of organ and tissue equivalent doses in radiation protection. METHODS: The study proposes a method for developing anatomically highly sophisticated pediatric phantoms without using medical images. The 5- and 10-year-old male and female phantoms presented here were developed using 3D modeling software applied to anatomical information taken from atlases and textbooks. The method uses polygon mesh surfaces to model body contours, the shape of organs as well as their positions, and orientations in the human body. Organ and tissue masses comply with the corresponding data given by the International Commission on Radiological Protection (ICRP) for the 5- and 10-year-old reference children. Bones were segmented into cortical bone, spongiosa, medullary marrow, and cartilage to allow for the use of micro computer tomographic (microCT) images of trabecular bone for skeletal dosimetry. RESULTS: The four phantoms, a male and a female for each age, and their organs are presented in 3D images and their organ and tissue masses in tables which show the compliance of the ICRP reference values. Dosimetric data, calculated for the reference pediatric phantoms by Monte Carlo methods were compared with corresponding data from adult mesh phantoms and pediatric stylized phantoms. The comparisons show reasonable agreement if the anatomical differences between the phantoms are properly taken into account. CONCLUSIONS: Pediatric phantoms were developed without using medical images of patients or volunteers for the first time. The models are reference phantoms, suitable for regulatory dosimetry, however, the 3D modeling method can also be applied to medical images to develop patient-specific phantoms.

Skeletal dosimetry for external exposures to photons based on microCT images of spongiosa: consideration of voxel resolution, cluster size, and medullary bone surfaces.

Skeletal dosimetry based on microCT images of trabecular bone has recently been introduced to calculate the red bone marrow (RBM) and the bone surface cell (BSC) equivalent doses in human phantoms for external exposure to photons. In order to use the microCT images for skeletal dosimetry, spongiosa voxels in the skeletons were replaced at run time by so-called micromatrices, which have exactly the size of a spongiosa voxel and contain segmented trabecular bone and marrow micro-voxels. A cluster (=parallelepiped) of 2 x 2 x 2 = 8 micromatrices was used systematically and periodically throughout the spongiosa volume during the radiation transport calculation. Systematic means that when a particle leaves a spongiosa voxel to enter into a neighboring spongiosa voxel, then the next micromatrix in the cluster will be used. Periodical means that if the particle travels through more than two spongiosa voxels in a row, then the cluster will be repeated. Based on the bone samples available at the time, clusters of up to 3 x 3 x 3 = 27 micromatrices were studied. While for a given trabecular bone volume fraction the whole-body RBM equivalent dose showed converging results for cluster sizes between 8 and 27 micromatrices, this was not the case for the BSC equivalent dose. The BSC equivalent dose seemed to be very sensitive to the number, form, and thickness of the trabeculae. In addition, the cluster size and/or the microvoxel resolution were considered to be possible causes for the differences observed. In order to resolve this problem, this study used a bone sample large enough to extract clusters containing up to 8 x 8 x 8 = 512 micro-matrices and which was scanned with two different voxel resolutions. Taking into account a recent proposal, this investigation also calculated the BSC equivalent dose on medullary surfaces of cortical bone in the arm and leg bones. The results showed (1) that different voxel resolutions have no effect on the RBM equivalent dose but do influence the BSC equivalent dose due to voxel effects by up to 5% for incident photon energies up to 200 keV, (2) that the whole-body BSC equivalent dose calculated with a cluster with 2 x 2 x 2 = 8 micromatrices is consistent with results received with clusters of up to 8 x 8 x 8 = 512 micromatrices, and (3) that for external whole-body exposure the inclusion of the BSC on medullary surfaces of cortical bone has a negligible effect on the whole-body BSC equivalent dose.

RADIATION DOSES TO ANAESTHETISTS DURING PROSTATIC ARTERY EMBOLIZATION INTERVENTIONAL PROCEDURES.

The objective of this study was to assess the radiation doses received by anaesthetists from prostatic artery embolization (PAE) procedures. Ten PAE procedures conducted in a reference hospital in the city of Recife, Brazil were investigated. Occupational dosimetry was performed using thermoluminescent dosemeters which were located next to the eyes, close to the thyroid (over the shielding), on the thorax (under the apron), on the wrist and on the feet of the physician's body. The results showed that the anaesthetist's feet received the highest doses followed by the eyes and the hands. In some complex PAE procedures the doses received by anaesthetists on the lens of the eyes and the effective dose were higher than those received by the main operator due to the anaesthetist's close position to the patient's table and the use of oblique projections. The personal dose equivalent Hp(3) per procedure for the anaesthetist's right eyebrow ranged from 20.2 µSv to 568.3 µSv. This result shows that anaesthetists assisting PAE procedures can exceeds the annual eye lens dose limit of 20 mSv recommended by the ICRP with only one procedure per week if radiation protection measures are not implemented during procedures.

Evaluation of the MOSkin dosimeter for diagnostic X-ray CT beams.

The aim of the present study was to evaluate the response of the MOSkin MOSFET dosimeter for X-ray diagnostic CT beams. Experiments were performed to investigate the sensitivity, energy dependence, reproducibility, fading and angular dependence of the dose response for the device. The dosimeter's performance was evaluated for the standard radiation qualities RQT 8, RQT 9 and RQT 10 in a metrology laboratory. In a CT scanner, the MOSkin was used to assess the air kerma profile and the dose profile in a phantom. The integral of the dose profile was compared to the CPMMA,100 measured with a pencil ionization chamber. The results showed that the MOSkin response was linear and reproducible with doses in the CT range. Energy dependence varied up to a factor of 1.19 among the tested X-ray energies. Angular dependence of the response was not greater than 7.8% within the angle range from 0 to 90 degrees. Signal fading within 3 min was negligible. Additionally, the MOSkin was able to accurately assess the air kerma profile and the integral of the dose profile in a CT scanner. The integral of the dose profile in a phantom was in agreement with the CPMMA,100. The presented results demonstrated the potential of the MOSkin for application in CT dosimetry.

Development of a realistic 3D printed eye lens dosemeter using CAD integrated with Monte Carlo simulation.

Recent epidemiological studies suggested to lower the threshold dose for radiation induced cataract in the eye lens. Therefore, eye lens radiation protection became to play a more important role in personal dosimetry. The main objective of this work is to propose a new methodology for prototyping and benchmarking of an eye lens dosimter based on the equivalent dose to the sensitive part of the eye lens, using CAD Software and Geant4 Monte Carlo simulations with mesh modelling and 3D printing. A 3D printed dosemeter was type tested based on IEC 62387:2012, in terms of energy and angular dependence for the measurements of Hp(3). The results show that the methodology employed is suitable for the development of new eye lens dosemeters.

REDUCTION OF STAFF RADIATION DOSE IN PROSTATIC ARTERY EMBOLISATION.

Prostatic artery embolisation (PAE) is used to treat patients with benign prostatic hyperplasia and with lower urinary obstructive tract symptoms. It is an interventional procedure which uses fluoroscopy equipment and can result in exposure to high doses of radiation in patients and staff. We aimed to demonstrate the reduction of radiation doses received by staff during PAE by implementing an optimised protocol called Radiation Exposure Curtailment for Embolisation (RECiFE). This protocol was implemented in cooperation with the medical team and technical team using Siemens Combined Applications to Reduce Exposure (CARE) protocol. The results showed approximately 83% reduction in the radiation doses received by the main physician during PAE. Thus, by adjusting the acquisition parameters of the angiographic equipment and implementing the RECiFE protocol, it is possible to optimise the PAE procedure and reduce the staff radiation dose.

CALDose_X-a software tool for the assessment of organ and tissue absorbed doses, effective dose and cancer risks in diagnostic radiology.

CALDose_X is a software tool that provides the possibility of calculating incident air kerma (INAK) and entrance surface air kerma (ESAK), two important quantities used in x-ray diagnosis, based on the output of the x-ray equipment. Additionally, the software uses conversion coefficients (CCs) to assess the absorbed dose to organs and tissues of the human body, the effective dose as well as the patient's cancer risk for radiographic examinations. The CCs, ratios between organ or tissue absorbed doses and measurable quantities, have been calculated with the FAX06 and the MAX06 phantoms for 34 projections of 10 commonly performed x-ray examinations, for 40 combinations of tube potential and filtration ranging from 50 to 120 kVcp and from 2.0 to 5.0 mm aluminum, respectively, for various field positions, for 29 selected organs and tissues and simultaneously for the measurable quantities, INAK, ESAK and kerma area product (KAP). Based on the x-ray irradiation parameters defined by the user, CALDose_X shows images of the phantom together with the position of the x-ray beam. By using true to nature voxel phantoms, CALDose_X improves earlier software tools, which were mostly based on mathematical MIRD5-type phantoms, by using a less representative human anatomy.

The performance of a multi guard ring (MGR) diode for clinical electron beams dosimetry.

The dosimetric response of a multi guard ring structure (MGR) diode has been studied with clinical electron beam energies from 5 MeV to 15 MeV. The results showed that the MGR dose response is linear in the range of 5-320 cGy and presents reproducibility with variation coefficients less than 0.4%. The field output factors measured with the MGR agreed within 2% with those measured with an ionization chamber. This study evidences that this diode can be used for clinical electron beam dosimetry.

Prognostic significance of early lymphocyte recovery after post-autografting administration of GM-CSF in non-Hodgkin's lymphoma.

The purpose of this study was to analyze the prognostic significance of early lymphocyte recovery after autologous SCT (ASCT) in the setting of routine post transplant administration of GM-CSF in patients with non-Hodgkin's lymphoma (NHL). This is a single institution retrospective comparative outcome analysis in a cohort of 268 relapsed chemosensitive NHL patients divided into two groups (early and late lymphocyte recovery) based on absolute lymphocyte counts (ALC) obtained on post transplant day +15 (ALC > or = 500, n=151 (56%) and ALC < 500, n=117 (44%)). Patient's characteristics were well-balanced between the two groups with regard to age, sex, preparative regimen, prior therapy, time from diagnosis to transplant and number of CD34+ cells infused. Post transplant complications were comparable in the two groups. Late lymphocyte recovery (ALC < 500 on day +15) was independently associated with a delay in platelet recovery (29 vs 21 days, P=0.0003) in patients who have not received pre-transplant rituximab. With a median follow-up of 22 months, no associations between early lymphocyte recovery and improvement of disease-free and overall survival were observed for either low- or intermediate-grade NHL. In conclusion, in this large single-centered retrospective analysis, where patients received routine post transplant GM-CSF, early lymphocyte recovery was not associated with favorable outcomes.

Skeletal dosimetry for external exposure to photons based on microCT images of spongiosa from different bone sites.

Micro computed tomography (microCT) images of human spongiosa have recently been used for skeletal dosimetry with respect to external exposure to photon radiation. In this previous investigation, the calculation of equivalent dose to the red bone marrow (RBM) and to the bone surface cells (BSC) was based on five different clusters of micro matrices derived from microCT images of vertebrae, and the BSC equivalent dose for 10 microm thickness of the BSC layer was determined using an extrapolation method. The purpose of this study is to extend the earlier investigation by using microCT images from eight different bone sites and by introducing an algorithm for the direct calculation of the BSC equivalent dose with sub-micro voxel resolution. The results show that for given trabecular bone volume fractions (TBVFs) the whole-body RBM equivalent dose does not depend on bone site-specific properties or imaging parameters. However, this study demonstrates that apart from the TBVF and the BSC layer thickness, the BSC equivalent dose additionally depends on a so-called trabecular bone structure (TBS) effect, i.e. that the contribution of photo-electrons released in trabecular bone to the BSC equivalent dose also depends on the bone site-specific structure of the trabeculae. For a given bone site, the TBS effect is also a function of the thickness of the BSC layer, and it could be shown that this effect would disappear almost completely, should the BSC layer thickness be raised from 10 to 50 microm, according to new radiobiological findings.

The safety of Bosutinib for the treatment of chronic myeloid leukemia.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are a potentially lifelong treatment for patients with chronic myeloid leukemia (CML). Adverse events (AEs) associated with TKIs are significant impediments in the daily life of patients that can impact compliance, and efficacy. Areas covered: This is a review on safety of bosutinib in the treatment of chronic phase CML. Data is extracted from the latest updates of bosutinib phase I/II and III trials. Expert opinion: Bosutinib is an effective agent against all phases of CML presently approved for the treatment in patients with resistance or intolerance to prior TKI therapy. Bosutinib has a unique toxicity profile characterized by early and transient diarrhea. Otherwise, the AE profile of bosutinib is comparable to other TKIs, with the exception of cardiovascular AEs that are infrequent in bosutinib-treated patients. Similar to other TKIs, the minimum effective dose of bosutinib remains unknown. Better definition of the optimal effective dose may spare, for those patients otherwise benefitting from treatment, unnecessary AEs.