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.

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.

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.

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.

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.

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 .).

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.

Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons.

Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic­periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger µCT images of TB.

Radioluminescence of rare-earth doped aluminum oxide.

Al(2)O(3):C is one of the most used radioluminescence materials for fiberoptic dosimetry due mainly to its high efficiency. However, this compound presents the drawback of emitting in the spectral region, where the spurious radioluminescence of fibers is also important. In this work, sintered samples of Al(2)O(3):C doped with Tb, Sm, Ce and Tm have been prepared by combustion synthesis and their radioluminescence responses have been evaluated. The influence of the different activators on the radioluminescence spectra has been investigated.

Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis.

Allogeneic hematopoietic SCT is an effective treatment in accelerated (AP) or blast phase (BP) CML. Imatinib (IM) has transient but significant activity in advanced phases of CML, which may permit early allografting for responding patients. To identify prognostic factors in allograft recipients previously treated with IM, we analyzed 449 allogeneic hematopoietic SCTs performed from 1999 to 2004 in advanced-phase CML, using the data reported to the Center for International Blood and Marrow Transplant Research. CML patients in second chronic phase (CP2, n=184), AP (n=185) and BP (n=80) received HLA-identical sibling (27%), related (3%), or matched or mismatched unrelated donor (70%), peripheral blood (47%) or BM (53%) hematopoietic SCT after myeloablative (78%) or non-myeloablative (22%) conditioning. In all, 52% in CP2, 49% in AP and 46% in BP received IM before hematopoietic SCT. Disease-free survival was 35-40% for CP2, 26-27% for AP and 8-11% for BP. Cumulative incidence of acute and chronic GVHD and TRM were not affected by the stages of CML or pre-hematopoietic SCT IM exposure. Multivariate analyses showed that conventional prognostic indicators remain the strongest determinants of transplant outcomes. In conclusion, there are no new prognostic indicators of the outcomes of allogeneic hematopoietic SCT for advanced-phase CML in the IM era.

Electron absorbed fractions of energy and S-values in an adult human skeleton based on µCT images of trabecular bone.

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on µCT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 µm thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters (14)C, (59)Fe, (131)I, (89)Sr, (32)P and (90)Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 µm endosteum and the previously recommended 10 µm endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by ∼20% when the beta emitters are in marrow.