Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods:Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n ¼ 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and antithyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P ¼ 0.04).Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
One of the most important aspects in the metrology of radiation fields is the problem of the measurement of dose profiles in regions where the dose gradient is large. In such zones, the 'detector size effect' may produce experimental measurements that do not correspond to reality. Mathematically it can be proved, under some general assumptions of spatial linearity, that the disturbance induced in the measurement by the effect of the finite size of the detector is equal to the convolution of the real profile with a representative kernel of the detector. In this work the exact relation between the measured profile and the real profile is shown, through the analytical resolution of the integral equation for a general type of profile fitting function using Gaussian convolution kernels.
Infants and children are a higher risk population for radiation cancer induction compared to adults. Although some values on pediatric patient doses for cardiac procedures have been reported, data to determine reference levels are scarce, especially when compared to those available for adults in diagnostic and therapeutic procedures. The aim of this study is to make a new contribution to the scarce published data in pediatric cardiac procedures and help in the determination of future dose reference levels. This paper presents a set of patient dose values, in terms of air kerma area product (KAP) and entrance surface air kerma (ESAK), measured in a pediatric cardiac catheterization laboratory equipped with a biplane x-ray system with dynamic flat panel detectors. Cardiologists were properly trained in radiation protection. The study includes 137 patients aged between 10 days and 16 years who underwent diagnostic catheterizations or therapeutic procedures. Demographic data and technical details of the procedures were also gathered. The x-ray system was submitted to a quality control programme, including the calibration of the transmission ionization chamber. The age distribution of the patients was 47 for <1 year; 52 for 1-<5 years; 25 for 5-<10 years and 13 for 10-<16 years. Median values of KAP were 1.9, 2.9, 4.5 and 15.4 Gy cm(2) respectively for the four age bands. These KAP values increase by a factor of 8 when moving through the four age bands. The probability of a fatal cancer per fluoroscopically guided cardiac procedure is about 0.07%. Median values of ESAK for the four age bands were 46, 50, 56 and 163 mGy, which lie far below the threshold for deterministic effects on the skin. These dose values are lower than those published in previous papers.
A method to carry out stoichiometric calibrations of CT scanners employed in radiotherapy treatment planning is proposed. The method is based on a simple parametrization of the CT number of a substance, which involves only two variables to describe the substance (electron density and one effective atomic number) and one parameter to describe the beam. The method was tested experimentally on a group of beams. A set of no tissue-like substances of known densities and elemental compositions were employed as calibrators. CT number-to-density curves (RED curves) were calculated with the proposed parametrization and compared to those measured with a commercial density phantom. Differences between the electron densities assigned by the calculated RED curves and the measured ones were in the range 0.009-0.019 (RMS). The proposed method may be employed to carry out accurate stoichiometric calibrations by using only one suitable substance as calibrator, not necessarily tissue-like.
Antral duplication cyst with an antral mucosal lining accounts for 2.2% of all gastric duplications, which represent 4-8% of all alimentary tract duplications. They usually become symptomatic before 2 years of age. We report a 6-year-old child with no previous history of symptoms who was admitted to our hospital because of frequent vomiting and acute abdominal pains for the previous 2 days. Abdominal examination revealed a mass in the epigastric area.
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