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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

Mathematical modelling of scanner-specific bowtie filters for Monte Carlo CT dosimetry.

The purpose of bowtie filters in CT scanners is to homogenize the x-ray intensity measured by the detectors in order to improve the image quality and at the same time to reduce the dose to the patient because of the preferential filtering near the periphery of the fan beam. For CT dosimetry, especially for Monte Carlo calculations of organ and tissue absorbed doses to patients, it is important to take the effect of bowtie filters into account. However, material composition and dimensions of these filters are proprietary. Consequently, a method for bowtie filter simulation independent of access to proprietary data and/or to a specific scanner would be of interest to many researchers involved in CT dosimetry. This study presents such a method based on the weighted computer tomography dose index, CTDIw, defined in two cylindrical PMMA phantoms of 16 cm and 32 cm diameter. With an EGSnrc-based Monte Carlo (MC) code, ratios CTDIw/CTDI100,a were calculated for a specific CT scanner using PMMA bowtie filter models based on sigmoid Boltzmann functions combined with a scanner filter factor (SFF) which is modified during calculations until the calculated MC CTDIw/CTDI100,a matches ratios CTDIw/CTDI100,a, determined by measurements or found in publications for that specific scanner. Once the scanner-specific value for an SFF has been found, the bowtie filter algorithm can be used in any MC code to perform CT dosimetry for that specific scanner. The bowtie filter model proposed here was validated for CTDIw/CTDI100,a considering 11 different CT scanners and for CTDI100,c, CTDI100,p and their ratio considering 4 different CT scanners. Additionally, comparisons were made for lateral dose profiles free in air and using computational anthropomorphic phantoms. CTDIw/CTDI100,a determined with this new method agreed on average within 0.89% (max. 3.4%) and 1.64% (max. 4.5%) with corresponding data published by CTDosimetry (www.impactscan.org) for the CTDI HEAD and BODY phantoms, respectively. Comparison with results calculated using proprietary data for the PHILIPS Brilliance 64 scanner showed agreement on average within 2.5% (max. 5.8%) and with data measured for that scanner within 2.1% (max. 3.7%). Ratios of CTDI100,c/CTDI100, p for this study and corresponding data published by CTDosimetry (www.impactscan.org) agree on average within about 11% (max. 28.6%). Lateral dose profiles calculated with the proposed bowtie filter and with proprietary data agreed within 2% (max. 5.9%), and both calculated data agreed within 5.4% (max. 11.2%) with measured results. Application of the proposed bowtie filter and of the exactly modelled filter to human phantom Monte Carlo calculations show agreement on the average within less than 5% (max. 7.9%) for organ and tissue absorbed doses.

Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin.

The oxidative pentose phosphate pathway (PPP) is crucial for cancer cell metabolism and tumor growth. We recently reported that targeting a key oxidative PPP enzyme, 6-phosphogluconate dehydrogenase (6PGD), using our novel small-molecule 6PGD inhibitors Physcion and its derivative S3, shows anticancer effects. Notably, humans with genetic deficiency of either 6PGD or another oxidative PPP enzyme, glucose-6-phosphate dehydrogenase, exhibit non-immune hemolytic anemia upon exposure to aspirin and various antimalarial drugs. Inspired by these clinical observations, we examined the anticancer potential of combined treatment with 6PGD inhibitors and antimalarial drugs. We found that stable knockdown of 6PGD sensitizes leukemia cells to antimalarial agent dihydroartemisinin (DHA). Combined treatment with DHA and Physcion activates AMP-activated protein kinase, leading to synergistic inhibition of human leukemia cell viability. Moreover, our combined therapy synergistically attenuates tumor growth in xenograft nude mice injected with human K562 leukemia cells and cell viability of primary leukemia cells from human patients, but shows minimal toxicity to normal hematopoietic cells in mice as well as red blood cells and mononucleocytes from healthy human donors. Our findings reveal the potential for combined therapy using optimized doses of Physcion and DHA as a novel antileukemia treatment without inducing hemolysis.

European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia.

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.

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.

Evaluation of staff, patient and foetal radiation doses due to endoscopic retrograde cholangiopancreatography (ERCP) procedures in a pregnant patient.

The use of endoscopic retrograde cholangiopancreatography (ERCP) in pregnant patients is not rare. Most studies on the safety and efficacy of these procedures report short- and long-term pregnancy outcomes and but not foetal absorbed doses. This investigation reports on an ERCP procedure for a 40-y-old woman who was 32-34 weeks pregnant. Thermoluminescent dosemeters (TLD 100) were used to measure doses received by the patient and the staff. Additionally, Monte Carlo calculations were performed using a 3D computational phantom representing a 9-month pregnant patient to estimate the foetal absorbed dose. The results show that the spleen of the mother received the largest absorbed dose of 12.18 mGy since it was closer to the source than other internal organs. For the foetus and uterus, the lowest absorbed dose was found to be 0.01 mGy to the foetal brain, while the largest absorbed dose was estimated to be 0.13 mGy to the placenta.

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.

Radiation exposure to patients and medical staff in hepatic chemoembolisation interventional procedures in Recife, Brazil.

The purpose of this study was to evaluate patient and medical staff absorbed doses received from transarterial chemoembolisation of hepatocellular carcinoma, which is the most common primary liver tumour worldwide. The study was performed in three hospitals in Recife, capital of the state of Pernambuco, located in the Brazilian Northeastern region. Two are public hospitals (A and B), and one is private (C). For each procedure, the number of images, irradiation parameters (kV, mA and fluoroscopy time), the air kerma-area product (PKA) and the cumulative air kerma (Ka,r) at the reference point were registered. The maximum skin dose (MSD) of the patient was estimated using radiochromic film. For the medical staff dosimetry, thermoluminescence dosemeters (TLD-100) were attached next to the eyes, close to the thyroid (above the shielding), on the thorax under the apron, on the wrist and on the feet. The effective dose to the staff was estimated using the algorithm of von Boetticher. The results showed that the mean value of the total PKA was 267.49, 403.83 and 479.74 Gy cm(2) for Hospitals A, B and C, respectively. With regard to the physicians, the average effective dose per procedure was 17 µSv, and the minimum and maximum values recorded were 1 and 41 µSy, respectively. The results showed that the feet received the highest doses followed by the hands and lens of the eye, since the physicians did not use leaded glasses and the equipment had no lead curtain.

Favorable impact of pre-transplant ATG on outcomes of reduced-intensity hematopoietic cell transplants from partially mismatched unrelated donors.

Reduced-intensity conditioning (RIC) permits allogeneic hematopoietic progenitor cell transplantation in patients who would not be considered candidates for transplantation using a myeloablative preparative regimen because of age, comorbidities or prior therapy. In the setting of myeloablative transplantation, use of antithymocyte globulin (ATG) can reduce the risk of GVHD without negatively affecting transplant outcomes; however, limited data exist on the impact of ATG in the setting of RIC, particularly when there is HLA-mismatch. We performed a retrospective analysis of 85 patients who received unrelated donor transplants at our institution for hematologic malignancies following conditioning with fludarabine and melphalan (FluMel), with or without rabbit ATG (6 mg/kg). ATG was targeted to patients receiving HLA-mismatched grafts. With a median follow-up of 36 months, those receiving ATG and a mismatched graft had similar rates of acute and chronic GVHD, relapse, and similar OS compared with those receiving HLA-matched grafts without ATG. In a multivariate analysis, HLA-mismatched donor was not associated with a decrement in OS. We conclude that this intermediate dose of ATG is effective in preventing severe GVHD in the setting of HLA-mismatch, without undue compromise of the graft versus tumor effects on which RIC transplants depend.