Myositis/myasthenia after pembrolizumab in a bladder cancer patient with an autoimmunity-associated HLA: Immune\u2013biological evaluation and case report

Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe immune-related (ir) adverse events (AEs). Here, we report the clinical and immune\u2013biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting

External dose-rate measurements based on smartphone CMOS sensors.

In the framework of the European Project CONFIDENCE ("COping with uNcertainties For Improved modelling and DEcision making in Nuclear emergenCiEs"), the characterization of two applications ("RadioactivityCounter and "GammaPix") that enable dose-rate measurements with an ordinary smartphone was carried out. In case of a nuclear emergency, such softwares allow to use the CMOS sensor of the built-in camera as a radiation detector. This paper presents the results of the scientific investigation on the reliability of the so-called "citizen measurements" performed with 14 different mobile phones chosen among the most common brands sold in 2017. All tests were carried out at room temperature and in different reference fields at the Secondary Standard Dosimetry Laboratory of the Helmholtz Zentrum Munchen. Investigated properties were the response at different dose-rate levels, influence of integration time, background, energy dependence and angular dependence

Reduction of uncertainties in exposure assessment based on environmental monitoring data.

Emergency preparedness and response systems for nuclear and radiological emergencies have to deal with decision-making in situations with relevant uncertainties. Consistent and appropriate protective measures must be decided before, during and after emergency situations. CONFIDENCE WP2 research helps to improve this decision-making process in the urgent response and the early response phase of emergency situations with potential major releases to atmosphere. This paper describes methods to reduce uncertainties in dose assessment for the population using data from stationary and mobile environmental monitoring programs. A special focus is given to identification of the measurement uncertainties of stationary and mobile monitoring systems. Methods to reduce these uncertainties and procedures to optimise mobile monitoring strategies are discussed. A first contribution towards assessing the quality of dose-rate measurements performed by the general population is made. In addition, the paper introduces approaches for advanced dose assessment tools using monitoring data and concepts for identifying critically exposed groups

Preliminary study of lithium tetraborate doped with Cu and in for external dosimetry.

A potentially tissue-equivalent dosimeter based on lithium tetraborate co-doped with Cu and In was successfully synthesized in two steps melting process. Basic material properties were characterized using Differential scanning calorimetry, X-ray diffraction, and Fourier Transform Infrared Spectroscopy, the dosimetric properties using Thermoluminescence. The highest sensitivity was observed for dopant concentrations of 0.1% Cu and 0.5% In. Tmax-Tstop analysis revealed the existence of eight individual peaks in the composite TL glow curve, which was confirmed by computerized glow curve deconvolution. A linear dose-response was seen up to about 30 Gy, for higher doses saturation effects occurred. The minimum detectable dose was estimated at about 670 μGy. TL peaks, with peak temperature above 150 °C faded to values between 3.3 and 14.9% of the respective of initial values after 70 days storage

Position paper on management of iron deficiency in adult cancer patients

Disorders of iron metabolism are commonly seen in onco-hematological clinical practice. Iron-deficiency anemia and cancer-associated anemia are usually treated with supportive therapies. Optimal management of these conditions are discussed in this perspective paper. Areas covered: A position paper discussing a number of hot topics on anemia in cancer patients is presented. The main areas covered by experts in the field are: definitions, prevalence and consequences of anemia and iron deficiency, incidence of anemia resulting from targeted therapies, importance of anemia diagnosis and monitoring, evaluation of iron status before and during treatment, role of transfusions and erythropoiesis-stimulating agents, management of iron deficiency with or without anemia, parenteral iron supplementation, role of new oral iron formulations, safety and cost issues regarding different iron compounds and administration routes. Expert commentary: Despite the availability of newer therapeutic options for its management, anemia still represents a major complication of treatment in cancer patients (surgery, chemotherapy, radiotherapy, targeted therapies), aggravating physical impairment, and negatively affecting general outcome. The view expressed by the panelists, attendees of the 4th Mediterranean Course on Iron Anemia, summarizes what they consider optimal clinical practice for screening, diagnosis, treatment and monitoring of iron deficiency and anemia in cancer patients

Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the BALLET Study on Patients Previously Treated Without and with Chemotherapy in the Metastatic Setting

BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The Oncologist 2017;22:1-8Implications for Practice: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis