31 research outputs found

    The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

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    Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAFV600E-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAFV600E status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAFV600E was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAFV600E-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAFV600E-negative tumors. Comparison of the BRAFV600E-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAFV600E-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAFV600E-negative sporadic tumors. Thus, BRAFV600E is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAFV600E-negative tumors

    Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident

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    With time after the Chernobyl accident, the number of papillary thyroid carcinomas (PTCs) driven by the BRAFV600E oncoprotein is growing in patients exposed to radiation at a young age. Clinicopathological associations of BRAFV600E in PTCs from patients with internal radiation history have not been sufficiently studied so far. This work analyzes the structural characteristics, proliferative activity, invasive features, clinical information, and dosimetric data in the BRAFV600E-positive and BRAFV600E-negative PTCs from the Ukrainian patients exposed to Chernobyl radiation and treated over 30 years after the accident. The study included 428 PTCs from patients aged 4–49 years at surgery who lived in the six northern regions of Ukraine most contaminated by 131I, were ≤18 years of age at the time of exposure, and were operated on from 1990 to 2017. Immunohistochemical staining for BRAFV600E was performed with the VE1 antibody. The probability of causation (POC) of a tumor due to radiation was determined using an interactive online NIH/NCI software. BRAFV600E was detected in 136/428 (31.8%) PTCs. In comparison with the BRAFV600E-negative PTCs, the BRAFV600E-positivity was associated with older patient age at the accident and at surgery, a longer period of latency, and lower POC. The BRAFV600E-positive PTCs were characterized by smaller tumor size, higher Ki67 labeling index, more frequent oncocytic changes, multifocality, and dominant papillary growth pattern. Tumor invasive features were less frequent in the BRAFV600E-positive PTCs and did not change with POC level. Despite a less aggressive tumor phenotype, BRAFV600E was a risk factor for recurrence, namely radioiodine-refractory (RAI-R) recurrent metastases. Multivariate models of RAI-R included BRAFV600E and/or histopathological parameters closely correlating with BRAFV600E such as tumor size, multifocality, dominant papillary growth pattern, or oncocytic changes. Thus, the BRAFV600E-positive PTCs from patients from a high-risk group for radiogenic thyroid cancer diagnosed in the 30 years after the Chernobyl accident did not display higher invasiveness regardless of POC level, but in view of the prognostic impact of this genetic alteration, knowledge of the BRAF status may be beneficial for middle-aged patients with radiogenic PTC considered for RAI therapy, and suggests more careful follow-up of patients with the BRAFV600E-positive tumors

    The high degree of similarity in histopathological and clinical characteristics between radiogenic and sporadic papillary thyroid microcarcinomas in young patients

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    The potential overtreatment of patients with papillary thyroid rocarcinoma(MPTC) has been an important clinical problem in endocrine oncology over the past decade. At the same time, current clinical guidelines tend to consider prior radiation exposure as a contraindication to less extensive surgery, even for lowrisk thyroid carcinomas, which primarily include microcarcinomas. This study aims to determine whether there are differences in the behavior of MPTC of two etiological forms (radiogenic and sporadic), including invasive properties, clinical data, and recurrence in patients aged up to 30 years. For this purpose, 136 radiogenic (from patients aged up to 18 years at the time of the Chornobyl accident) and 83 sporadic (from patients born after the Chornobyl accident) MPTCs were selected and compared using univariate and multivariate statistical methods in a whole group and in age and tumor size subgroups. No evidence of more aggressive clinical and histopathological behavior of radiogenic MPTCs as compared to sporadic tumors for basic structural, invasive characteristics, treatment options, and postoperative follow-up results was found. Moreover, radiogenic MPTCs were characterized by the lower frequencies of oncocytic changes (OR = 0.392, p = 0.004), nodal disease (OR = 0.509, p = 0.050), and more frequent complete remission (excellent response) after radioiodine therapy (OR = 9.174, p = 0.008). These results strongly suggest that internal irradiation does not affect tumor phenotype, does not associate with more pronounced invasive properties, and does not worse prognosis in pediatric or young adult patients with MPTC, implying that radiation history may be not a pivotal factor for determining treatment strategy in such patients

    The relationship of the clinicopathological characteristics and treatment results of post-Chornobyl papillary thyroid microcarcinomas with the latency period and radiation exposure

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    Introduction: A worldwide increase in the incidence of thyroid cancer during the last decades is largely due to papillary thyroid microcarcinomas (MPTCs), which are mostly low-risk tumors. In view of recent clinical recommendations to reduce the extent of surgery for low-risk thyroid cancer, and persisting uncertainty about the impact of radiation history, we set out to address whether clinicopathological characteristics and prognosis of post-Chornobyl MPTCs were changing with regard to: i) the latency period, ii) probability of causation (POC) of a tumor due to radiation, and iii) tumor size.Methods: Patients (n = 465) aged up to 50 years at diagnosis who lived in April, 1986 in six northern, most radiocontaminated regions of Ukraine were studied.Results: Latency period was statistically significantly associated with the reduction of POC level, tumor size and the frequency of fully encapsulated MPTCs. In contrast, the frequency of oncocytic changes and the BRAFV600E mutation increased. Invasive properties and clinical follow-up results did not depend on latency except for a lower frequency of complete remission after postsurgical radioiodine therapy. The POC level was associated with more frequent extrathyroidal extension, and lymphatic/vascular invasion, less frequent oncocytic changes and BRAFV600E, and did not associate with any clinical indicator. Tumor size was negatively associated with the latency period and BRAFV600E, and had a statistically significant effect on invasive properties of MPTCs: both the integrative invasiveness score and its components such as lymphatic/vascular invasion, extrathyroidal extension and lymph node metastases increased. The frequency of total thyroidectomy, neck lymph node dissection and radioiodine therapy also increased with the larger tumor size. The duration of the latency period, POC level or tumor size did not associate with the chance of disease recurrence.Discussion: In summary, we did not observe overall worsening of the clinicopathological features or treatment results of radiogenic MPTCs that could be associated with the latency period or POC level, suggesting that radiation history did not strongly affect those in the analyzed MPTC patients. However, the increase in the invasive properties with tumor size indicates the need for individual risk stratification for each MPTC patient, regardless of radiation history, for treatment decision-making

    The relationship of the clinicopathological characteristics and treatment results of post-Chornobyl papillary thyroid microcarcinomas with the latency period and radiation exposure

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    IntroductionA worldwide increase in the incidence of thyroid cancer during the last decades is largely due to papillary thyroid microcarcinomas (MPTCs), which are mostly low-risk tumors. In view of recent clinical recommendations to reduce the extent of surgery for low-risk thyroid cancer, and persisting uncertainty about the impact of radiation history, we set out to address whether clinicopathological characteristics and prognosis of post-Chornobyl MPTCs were changing with regard to: i) the latency period, ii) probability of causation (POC) of a tumor due to radiation, and iii) tumor size.MethodsPatients (n = 465) aged up to 50 years at diagnosis who lived in April, 1986 in six northern, most radiocontaminated regions of Ukraine were studied.ResultsLatency period was statistically significantly associated with the reduction of POC level, tumor size and the frequency of fully encapsulated MPTCs. In contrast, the frequency of oncocytic changes and the BRAFV600E mutation increased. Invasive properties and clinical follow-up results did not depend on latency except for a lower frequency of complete remission after postsurgical radioiodine therapy. The POC level was associated with more frequent extrathyroidal extension, and lymphatic/vascular invasion, less frequent oncocytic changes and BRAFV600E, and did not associate with any clinical indicator. Tumor size was negatively associated with the latency period and BRAFV600E, and had a statistically significant effect on invasive properties of MPTCs: both the integrative invasiveness score and its components such as lymphatic/vascular invasion, extrathyroidal extension and lymph node metastases increased. The frequency of total thyroidectomy, neck lymph node dissection and radioiodine therapy also increased with the larger tumor size. The duration of the latency period, POC level or tumor size did not associate with the chance of disease recurrence.DiscussionIn summary, we did not observe overall worsening of the clinicopathological features or treatment results of radiogenic MPTCs that could be associated with the latency period or POC level, suggesting that radiation history did not strongly affect those in the analyzed MPTC patients. However, the increase in the invasive properties with tumor size indicates the need for individual risk stratification for each MPTC patient, regardless of radiation history, for treatment decision-making

    Radiation-Induced Cerebro-Ophthalmic Effectsin Humans

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    : Exposure to ionizing radiation (IR) could affect the human brain and eyes leading to both cognitive and visual impairments. The aim of this paper was to review and analyze the current literature, and to comment on the ensuing findings in the light of our personal contributions in this field. The review was carried out according to the PRISMA guidelines by searching PubMed, Scopus, Embase, PsycINFO and Google Scholar English papers published from January 2000 to January 2020. The results showed that prenatally or childhood-exposed individuals are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. In adulthood and medical/interventional radiologists, the most frequent IR-induced ophthalmic effects include cataracts, glaucoma, optic neuropathy, retinopathy and angiopathy, sometimes associated with specific neurocognitive deficits. According to available information that eye alterations may induce or may be associated with brain dysfunctions and vice versa, we propose to label this relationship “eye-brain axis”, as well as to deepen the diagnosis of eye pathologies as early and easily obtainable markers of possible low dose IR-induced brain damage

    Radiation risk estimation: based on measurement error models

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    This monograph discusses statistics and risk estimates applied to radiation damage under the presence of measurement errors. The first part covers nonlinear measurement error models, with a particular emphasis on efficiency of regression parameter estimators. In the second part, risk estimation in models with measurement errors is considered. Efficiency of the methods presented is verified using data from radio-epidemiological studies

    Methods for Estimation of Radiation Risk in Epidemiological Studies Accounting for Classical and Berkson Errors in Doses

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    With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)−1, R = λ0 + EAR D, where λ0 is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes=fiQimes/Mimes. Here, Qimes is the measured content of radioiodine in the thyroid gland of person i at time tmes, Mimes is the estimate of the thyroid mass, and fi is the normalizing multiplier. The Qi and Mi are measured with multiplicative errors ViQ and ViM, so that Qimes=QitrViQ (this is classical measurement error model) and Mitr=MimesViM (this is Berkson measurement error model). Here, Qitr is the true content of radioactivity in the thyroid gland, and Mitr is the true value of the thyroid mass. The error in fi is much smaller than the errors in ( Qimes, Mimes) and ignored in the analysis

    Methods for Estimation of Radiation Risk in Epidemiological Studies Accounting for Classical and Berkson Errors in Doses

    No full text
    With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)-1, R = λ0 + EAR D, where λ0 is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes = fiQimes/Mimes. Here, Qimes is the measured content of radioiodine in the thyroid gland of person i at time tmes, Mimes is the estimate of the thyroid mass, and fi is the normalizing multiplier. The Qi and Mi are measured with multiplicative errors ViQ and ViM, so that Qimes = QitrViQ (this is classical measurement error model) and Mitr = MimesViM (this is Berkson measurement error model). Here, Qitr is the true content of radioactivity in the thyroid gland, and Mitr is the true value of the thyroid mass. The error in fi is much smaller than the errors in (Qimes, Mimes) and ignored in the analysis.

    The BRAFV600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age

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    SIMPLE SUMMARY: Analysis of the groups of young Ukrainian patients (aged ≤28 years) with radiogenic and sporadic papillary thyroid carcinomas (PTCs) showed that the frequency of BRAF(V600E) was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAF(V600E)-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAF(V600E)-negative tumors. Comparison of the BRAF(V600E)-positive PTCs across the groups found a virtual absence of differences, while the BRAF(V600E)-negative tumors differed markedly and displayed a higher frequency of invasive tumor features in the radiogenic PTCs. Hence, there is evidence that BRAF(V600E) does not confer a more aggressive course of PTC in young patients regardless of tumor etiology. ABSTRACT: Histopathological changes in the fusion oncogene-driven papillary thyroid carcinomas (PTCs) from children and adolescents exposed to Chernobyl fallout have been extensively studied. However, characteristics of the radiogenic BRAF(V600E)-positive PTCs, whose proportion is growing with time, are not well described yet. We analyzed the relationship between the BRAF(V600E) status (determined immunohistochemically with the VE1 antibody) and the clinicopathological features of 247 radiogenic and 138 sporadic PTCs from young Ukrainian patients aged ≤28 years. The frequency of BRAF(V600E) was increasing with patient age, consistently remaining lower in radiogenic PTCs. In both etiopathogenic groups, the BRAF(V600E)-positive PTCs more frequently had a dominant papillary growth pattern, smaller tumor size, higher Ki67 labeling index, and a frequency of the major indicators of tumor invasiveness that is lower than or equal to that of the BRAF(V600E)-negative tumors. Comparison of the BRAF(V600E)-positive PTCs across the groups found a virtual absence of differences. In contrast, the BRAF(V600E)-negative radiogenic PTCs displayed less frequent dominant papillary and more frequent solid growth patterns, lower Ki67 labeling index, and higher invasiveness than the BRAF(V600E)-negative sporadic tumors. Thus, BRAF(V600E) is not associated with a more aggressive course of PTC in young patients regardless of etiology. The major clinicopathological differences between the radiogenic and sporadic PTCs are observed among the BRAF(V600E)-negative tumors
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