BAlloon expandable vs. SElf expanding transcatheter vaLve for degenerated bioprosthesIs: design and rationale of the BASELINE trial.

BACKGROUND: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. METHODS: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. CONCLUSIONS: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072).

The EANM guideline on radioiodine therapy of benign thyroid disease.

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

Differentiated thyroid cancer: Case report of false positive 131I uptake on whole body scintigraphy in a patient with bilateral femur osteonecrosis.

OBJECTIVE: Differentiated thyroid cancer (DTC) is one of the fastest growing cancers worldwide. Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, exhibiting a more aggressive behavior. Radioiodine whole-body scintigraphy (WBS) has been used in the detection of DTC. Radioiodine is a sensitive marker for detection of thyroid cancer; however, radioiodine uptake is not specific for thyroid tissue. It can also be seen in healthy tissue as well as in inflammation, or in a variety of benign and malignant non-thyroidal entities. SUBJECT AND METHODS: The subject of the present case report is a 52 years old man with brain metastatic DTC who received radioiodine therapy and corticosteroids as palliative therapy. Whole-body scintigraphy revealed bilateral iodine uptake of the femur. Corticosteroid therapy is among the most widely recognized risk factor for osteonecrosis, which at the present case had to be recognized as a false positive (iodine-131) 131I uptake in order to avoid diagnostic error. RESULTS: Post therapeutic whole body scintigraphy revealed no uptake in the thyroid bed as well as pathologic uptake of radioiodine in both femurs. The magnetic resonance imaging (MRI) of the femurs combined with the history of long term exposition on high doses of corticosteroids evidenced diagnosis of steroid-induced osteonecrosis of the femurs. CONCLUSION: Radioiodine WBS plays an important role in clinical decision making for the evaluation and the management of patients with DTC. Despite its high range of sensitivity and specificity, a variety of reports of false positive whole body scans has demonstrated a diversity of causes. Comprehension of the physiology of iodine uptake and of the pathophysiology of clinical entities which end up giving false positives scans, provides clinicians a useful tool in order to avoid diagnostic and therapeutic errors as far as DTC is concerned.

Variations in Radioiodine Therapy in Europe: Decision-Making after Total Thyroidectomy.

The role of radioiodine therapy (RIT) (used as ablation therapy or adjuvant therapy) following total thyroidectomy for differentiated thyroid cancer (DTC) changed. Major revisions of the American Thyroid Association (ATA) Guidelines in 2015 resulted in significant differences in treatment recommendations in comparison to the European Association of Nuclear Medicine (EANM) 2008 guidelines. Recently, we presented the effects on daily practice for RIT among Swiss Nuclear Medicine centres. We now performed a study at the European level and hypothesized that there is also considerable variability among European experts. We performed a decision-tree-based analysis of management strategies from all members of the EANM thyroid committee to map current practice among experts. We collected data on whether or not RIT is administered, on which criteria these decisions are based and collected details on treatment activities and patient preparation. Our study shows discrepancies for low-risk DTC, where "follow-up only" is recommended by some experts, while RIT with significant doses is used by other experts. E.g., for pT1b tumours without evidence of metastases, the level of agreement for the use of RIT is as low as 50%. If RIT is administered, activities of I-131 range from 1.1 GBq to 3.0 GBq. In other constellations (e.g., pT1a), experts diverge from current clinical guidelines as up to 75% administer RIT in certain cases. For intermediate and high-risk patients, RIT is generally recommended. However, dosing and treatment preparation (rhTSH vs. thyroid hormone withdrawal) vary distinctly. In comparison to the Swiss study, the general level of agreement is higher among the European experts. The recently proposed approach on the use of RIT, based on integrated post-surgery assessment (Martinique article) and results of ongoing prospective randomized studies are likely to reduce uncertainty in approaching RIT treatment. In certain constellations, consensus identified among European experts might be helpful in formulating future guidelines.

SPECT analysis and language profile in Greek speaking patients with subtypes of frontotemporal dementia.

OBJECTIVE: We aimed to examine if single photon emission computed tomography (SPECT) can discriminate between variants of frontotemporal dementia (FTD). As a secondary investigation we identify and establish the linguistic differences between those variants. MATERIALS AND METHODS: Nine patients with semantic variant primary progressive aphasia (svPPA), 8 with non-fluent variant primary progressive aphasia (nfvPPA) and 17 with behavioral variant of frontotemporal dementia (bvFTD) were compared on Addenbrooke's cognitive examination-revised (ACE-R), auditory comprehension, oral expression and verbal fluency. All patients were also compared with healthy controls. Patients were evaluated using technetium-99m-hexamethylproyleneamine oxime (99mTc-HMPAO) brain SPECT as a measure of regional cerebral flow. RESULTS: Significant group differences between all patients and controls were found for ACE-R, auditory comprehension and oral expression. Semantic variant primary progressive aphasia patients performed higher in letter compared to category fluency with significant deficits in auditory comprehension and oral expression. Non-fluent variant primary progressive aphasia patients showed significant deficits in auditory comprehension but not oral expression while performed lightly worse in letter fluency compared to category. Behavioral variant of frontotemporal dementia patients showed deficits in auditory comprehension and oral expression and performed similar in category and letter fluency. Single photon emission computed tomography analysis revealed left frontotemporal hypoperfusion extending to the right frontotemporal region in svPPA patients. Non-fluent variant primary progressive aphasia patients presented left frontotemporal hypoperfusion with participation of the left parietal and right frontotemporal regions. Behavioral variant of frontotemporal dementia patients showed bilateral frontotemporal hypoperfusion compared to parietal and visual cortices. CONCLUSION: Our findings suggest that SPECT may assist in the discrimination of the FTD variants. We also confirmed that bvFTD patients share similar language deficits with svPPA patients.

A novel quantitative method for assessing the therapeutic response to Tafamidis therapy in patients with cardiac TTR amyloidosis. A preliminary report.

OBJECTIVE: Cardiomyopathy is a common manifestation of transthyretin amyloidosis (ATTR), leading to heart failure, associated with high morbidity and mortality. The aim of this study was to investigate the effect of Tafamidis treatment by means of cardiac radiotracer uptake on myocardial scintigraphy. SUBJECTS AND METHODS: Five male patients, mean age 76.2 years, with wild-type ATTR were included in the protocol. Total body scanning using technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (in four patients) and technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) (in one) was performed pre- and one year post-Tafamidis therapy. A novel quantitation method for assessing radiotracer cardiac uptake was employed. The geometric mean was computed for both cardiac and thigh region of interest (ROI) and the heart-to-thigh (HtT) ratio was assessed by dividing the corresponding geometric mean counts. RESULTS: Heart-to-thigh ratio was improved (decreased) in four of the patients receiving Tafamidis, in keeping with lower uptake to the cardiac region. These patients also demonstrated a relatively favorable clinical response to Tafamidis. The patient evaluated by 99mTc-HMDP exhibited minimal HtT ratio reduction and stable clinical and echocardiographic characteristics. CONCLUSION: Sequential HtT ratio measurements could potentially identify patients with a favorable response to Tafamidis treatment at earlier stages, compared to other imaging modalities or serological biomarkers.

Higher thyroid hormone levels and cancer.

PURPOSE: This narrative review aims to summarize the relationship between hyperthyroidism, upper reference range thyroid hormone (TH) levels, and cancer, and to address the clinical management of hyperthyroidism in cancer patients. METHODS: A comprehensive search was performed by an independent reviewer through Google Scholar and PubMed Electronic databases. All searches were restricted to English language manuscripts published between 2000 and 2020. RESULTS: Numerous in vitro, in vivo, and population-based studies suggest cancer-stimulating effect of triiodothyronine and thyroxin. THs are presented as mediators for tumor growth, proliferation, and progression. Many population and case-control studies suggest an increased risk of several solid but also hematologic malignancies in relation to hyperthyroidism and upper normal range TH levels. However, results are not unambiguous. In this review, we will summarize population and case-control studies that investigated the relationship between hyperthyroidism, upper reference range TH levels, lower thyrotropin (TSH) levels, lower reference range TSH levels with cancer risk, cancer prognosis, and cancer outcome. The vast majority of evidence suggests an association between clinical and subclinical hyperthyroidism with the risk of developing several types of cancer. Furthermore, hyperthyroidism is also linked with a poorer cancer prognosis. In this review, we will also discuss the diagnosis of hyperthyroidism in patients with pre-existing cancer and cover the management of hyperthyroidism in cancer patients, with special attention on the role of nuclear medicine. CONCLUSIONS: It is crucial to emphasize the importance of the rapid establishment of euthyroidism, and consequently, the importance of radioiodine therapy, as the therapy of choice in most cancer patients. We want to show that in this day and age there still is a high relevance for I-131 to achieve a permanent solution and thus likely reduce the risk of adverse influence of hyperthyroidism on the occurrence of new and course of existing cancer cases.

One-year clinical and echocardiographic outcomes of direct implantation of a self-expanding valve.

OBJECTIVE: To present 1 year clinical and echocardiographic outcomes of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial. BACKGROUND: Intermediate-term data from randomized studies investigating the safety and efficacy of direct implantation are lacking. METHODS: DIRECT trial randomized 171 consecutive patients with severe aortic stenosis at four tertiary centers to undergo TAVI with the use of self-expanding prostheses with (pre-BAV) or without pre-dilatation (no-BAV). The primary endpoint was device success according to the VARC-2 criteria. All patients underwent a clinical and echocardiographic follow-up at 1 year. All-cause and cardiac mortality, stroke, heart failure hospitalization, and new pacemaker implantation were recorded. RESULTS: At 1 year, four deaths were recorded in pre-BAV group (4.7%) and three deaths in no-BAV group (3.5%). There was no difference in Kaplan-Meier plots between the two groups in all-cause mortality at 1 year (log-rank p = .72). Similarly, there was no difference in the incidence of permanent pacemaker implantation between the two groups at 1 year (27/67-40.3% in no-BAV group versus 20/69-29% in pre-BAV group, log-rank p = .24). There was no significant difference between pre-BAV and no BAV group in aortic valve area (1.84 ± 0.39 cm2 vs. 1.85 ± 0.44 cm2 , p = .90), mean aortic valve gradient (8.36 ± 5.04 vs. 8.00 ± 4.04 mmHg, p = .65) and moderate or severe paravalvular regurgitation (5-6.6 vs. 4-5.7%, respectively) at 1 year. The same applied independently from the performance of post-dilatation at baseline. CONCLUSIONS: Direct, without pre-dilatation, implantation of a self-expanding valve has no impact on one-year clinical and echocardiographic outcomes, independently also from the baseline performance of post-dilatation.

Theragnostics before we found its name.

Theragnostics embraces "gnosis" and "prognosis" and concerns a treatment strategy which combines diagnostics with therapeutics. The birth of what we call today theragnostics can be traced in 1936, with the proposal of radioiodine, the first radiopharmaceutical approved in 1951 by FDA, in USA, as 131I sodium iodide. In 1957, 89Sr was also approved as first therapeutic radiotracer for skeletal metastases, followed in the subsequent years by 186Rh, 153Sm and, more recently, 223Ra, the first alpha emitter clinically utilized, allowing curative results and not only a palliative effect. Proposed in first eighties as [131I] Metaiodobenzylguanidine (MIBG), the theragnostic couple 123I/131I MIBG is still used in neural crest tumors, while, starting from partially unsatisfactory results in 70's, models based on antibodies for radioimmunoscintigraphy/radioimmunotherapy have been subsequently upgraded thanks to the introduction of monoclonal antibodies and other significant biological and technical improvements. The "Theragnostics called with this name" can be dated to early 90's with the first proposal of the somatostatin model, actually widely operating in neuroendocrine tumors with radio-chelates usable for diagnosis and therapy. Since then, many investigators are working on new theragnostics agents, also outside of the nuclear medicine, based on peptides, antibodies and other tools to find new models applicable in the clinical practice. The fast growth is stimulated by the interest of big pharma. Theragnostic concepts are the roots of nuclear medicine and new great goals are soon to be achieved in the direction of an increasing precision and tailored medicine.

Vitamin D Deficiency as a Risk Factor for Myocardial Ischemia.

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≥4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10-29 ng/mL and ≥30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = -0.232, p = 0.014) and SRS (rho = -0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia.

EANM practice guideline for PET/CT imaging in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumour derived from the para-follicular thyroid C cells. It may occur in sporadic or hereditary forms and surgery represent the primary cure. METHODS: Ultrasound examination and, in selected cases, cross-sectional anatomic imaging procedures, are adopted to stage the disease before primary surgery while different anatomic/morphologic and functional/molecular imaging procedures can be adopted in detecting persistent/recurrent disease. Positron emitting radiopharmaceuticals including fluorine-18 fluorodeoxyglucose (18F-FDG), fluorine-18 dihydroxyphenylalanine (18F-FDOPA) and somatostatin analogues labelled with gallium-68 (68Ga-SSA) tracks different metabolic pathways or receptor expression/functioning, and proved to be useful in detecting MTC recurrences/metastasis. CONCLUSIONS: This practice guideline from the Thyroid Committee of the European Association of Nuclear Medicine (EANM), with involvement of external experts, provides recommendations based on updated literature's evidences. The purpose of this practice guideline is to assist imaging specialists and clinicians in recommending, performing and interpreting the results of PET/CT with various radiopharmaceuticals in patients with MTC.

Nuclear thyroidology in pandemic times: The paradigm shift of COVID-19.

Since its outbreak in Wuhan, China the SARS-CoV-2 has become a public health emergency of international concern, impacting all areas of daily life, including medical care. Although not in the front line nuclear medicine practice should adjust their standard operating procedures. The adaptations and the flexibility that nuclear thyroidology, among other fields of nuclear medicine, should show during the pandemic, must focus not only in minimizing the risk of infection to staff, patients, and family members, but also in controlling the transmission of the virus while continuing to provide health care services which do not jeopardize patients' prognosis and quality of life. Favorable prognosis and indolent symptoms of most cases of thyroid diseases, allows postponements and rescheduling as well as alternative procedures, provided that they are cautiously considered for each case individually. The objective of the current paper is to provide guidance on how diagnostic and therapeutic management of patients with thyroid diseases can be safely and effectively adjusted during pandemic, in nuclear medicine settings.

Associating radioiodine therapy in hyperthyroidism with cancer mortality: robust or random results of a statistical analysis?

Dear Editor, Recently, Kitahara et al. (2019) published an article in JAMA Internal Medicine entitled "Association of radioactive iodine treatment with cancer mortality in patients with hyperthyroidism". This publication was based on organ dosimetry calculations from 18,805 patients with hyperthyroidism treated with radioiodine treatment (RAI) followed for nearly 7 decades. The results of the work suggest that solid cancer mortality increases in hyperthyroid patients treated with RAI, with greater absorbed doses to exposed organs being associated with increased risk of death. As expected, these -undoubtedly interesting- findings have raised serious concerns in both physicians and patients regarding the safety profile of RAI. Driven by this, we aim to critically read the article and highlight some of the limitations of the study. First of all, the authors provide data on the association of RAI with cancer mortality and not with cancer incidence, which may be an interesting approach, but constitutes at the same time a weakness of the study. The authors' choice to investigate RAI as a progression and not as an actual risk factor for the onset of malignancies in hyperthyroid patients may be interpreted as an inability to document a causal relationship between them. It would be methodologically more correct either to examine as confounders -among others- cancer stage, patients' age and other co-morbidities, previous treatment administered, or to declare the absence of these data as a major limitation of the conducted analysis. Moreover, the negligence of the role of thyroid hormone levels is another fundamental limitation of this analysis, since a large body of the literature has documented the association of increased thyroid hormone levels with carcinogenicity. In their introduction, the authors state that RAI has declined in favor of antithyroid drugs (ATD). This trend is attempted to be explained by the "increased awareness" of an association between RAI and Graves ophthalmopathy exacerbation as well as radiation-induced secondary malignancies. This argument has however little supporting evidence, since several studies demonstrate that ATD remain the least commonly used agents through the last decades. Moreover, the authors neglect that ATD carry a statistically significant and more obvious cancer death risk than RAI. On the other hand, the use of RAI as index therapy has been doubled through the decades, influenced by several causes including patient-, disease-, physician- and health system- related factors and, of course, not only patients' and physicians' "increased awareness". In addition, concerns are raised regarding organ dosimetry calculations with large uncertainties introduced in the analysis due to reported errors in measured thyroid uptake and mass as well as same model parameters used for patients with different thyroid entities. As Tulchinsky and Bertrand Brill -the Nuclear Medicine physician coauthors of the JAMA paper- state, 'the Kitahara et al. (2019) publication provides a numerical estimate of excess cancer deaths after RAI using assumptive model-based calculations' but 'no excess cancer deaths were actually observed after RAI relative to that predicted in contemporaneous population (using standardized mortality ratio analyses)'. Further, the authors report that "Malignancy was the primary cause for 2,366 deaths (15.3%)" without mentioning other causes of death. However, it would be appropriate to provide some data at least on cardiovascular disease (CVD)-related mortality given that thyrotoxicosis has been associated with CVD by a large number of studies. Some other methodological limitations include the lack of more appropriate control groups for comparison, such as hyperthyroid patients treated with other treatments (surgery, ATD or both), hyperthyroid patients without treatment, as well as euthyroid patients. Finally, the lack of multivariate analyses for all the aforementioned confounders as well as the lack of detailed description of "Other risk factors (x)" in the applied model: "background (a, s, b, x)[1+ßd*f(y)]" constitute methodological drawbacks of the analysis. The key-point of the analysis-thankfully mentioned by the authors- is summarized by the phrase: "some results may be because of chance; therefore, the results should be interpreted with caution." And we could not agree more.

Gender-related differences in side-effects and hemodynamic response to regadenoson in patients undergoing SPECT myocardial perfusion imaging.

PURPOSE: To evaluate differences in side-effects and hemodynamic response between men and women undergoing regadenoson-stress SPECT myocardial perfusion imaging (MPI). METHODS: The initial population of the study included 858 consecutive patients who underwent regadenoson-stress MPI at our institution. These patients underwent prospective assessment and classification of regadenoson-induced side-effects in six categories and recording of heart rate (HR) and blood pressure (BP) before and after regadenoson administration. From this initial population, after adjustment with 1:1 propensity matching using gender as the dependent variable and age, BMI, diabetes mellitus, hypertension, smoking, presence of coronary artery disease, LVEF, baseline systolic and diastolic blood pressure (BP) and HR, on-going use of cardio-active medications during test, and abnormal MPI scan as independent variables, a population of 279 pairs of opposite gender was formed and studied. RESULTS: Compared with men, women had a significantly higher rate of any side-effect (71% vs. 58%, p = 0.002), chest pain (23% vs. 12%, p < 0.001), gastrointestinal discomfort (20% vs. 12%, p = 0.01), dizziness (12% vs. 5%, p = 0.002), and headache (20% vs. 13%, p = 0.03) and similar rates of dyspnea and other side-effects. Women demonstrated a higher median HR-response compared with men (41% (- 8, 127) vs. 34% (- 5, 106), p = 0.001) while men demonstrated a lower median systolic BP response (- 3% (- 27, 48) vs. 0% (- 36, 68), p = 0.02) compared with women. CONCLUSIONS: Gender is independently associated with a differential response to regadenoson with regard to overall side-effects and HR-response. These observations have the potential of important management and prognostic implications respectively.

EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy.

INTRODUCTION: Scintigraphic evaluation of the thyroid gland enables determination of the iodine-123 iodide or the 99mTc-pertechnetate uptake and distribution and remains the most accurate method for the diagnosis and quantification of thyroid autonomy and the detection of ectopic thyroid tissue. In addition, thyroid scintigraphy and radioiodine uptake test are useful to discriminate hyperthyroidism from destructive thyrotoxicosis and iodine-induced hyperthyroidism, respectively. METHODS: Several radiopharmaceuticals are available to help in differentiating benign from malignant cytologically indeterminate thyroid nodules and for supporting clinical decision-making. This joint practice guideline/procedure standard from the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides recommendations based on the available evidence in the literature. CONCLUSION: The purpose of this practice guideline/procedure standard is to assist imaging specialists and clinicians in recommending, performing, and interpreting the results of thyroid scintigraphy (including positron emission tomography) with various radiopharmaceuticals and radioiodine uptake test in patients with different thyroid diseases.

Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data.

Background and Objective: Radium-223 dichloride (Xofigo®) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. This targeted, α-particle-emitting therapy has demonstrated significant survival benefit accompanied by a favorable safety profile. Nevertheless, recent evidence suggests that its combined use with abiraterone and prednisone/prednisolone may be associated with increased risk of death and fractures. While the precise pathophysiologic mechanisms of these events are not yet clear, collecting evidence from more clinical trials and translational studies is necessary. The aim of our present study is to assess whether accessible sources of patient outcome data can help gain additional clinical insights to radium-223 dichloride's safety profile. Materials and Methods: We performed a retrospective analysis of cases extracted from the FDA Adverse Event Reporting System and characterized side effect occurrence by using reporting ratios. Results: A total of ~1500 prostate cancer patients treated with radium-223 dichloride was identified, and side effects reported with the use of radium-223 dichloride alone or in combination with other therapeutic agents were extracted. Our analysis demonstrates that radium-223 dichloride may often come with hematological-related reactions, and that, when administered together with other drugs, its safety profile may differ. Conclusions: While more prospective studies are needed to fully characterize the toxicological profile of radium-223 dichloride, the present work constitutes perhaps the first effort to examine its safety when administered alone and in combination with other agents based on computational evidence from public real-world post marketing data.

Long term quality of life in differentiated thyroid cancer patients after thyroidectomy and high doses of 131I with or without suppressive treatment.

According to international guidelines, the most frequently applied diagnostic procedures and therapeutic interventions for differentiated thyroid cancer (DTC) patients are those of nuclear medicine. Differentiated thyroid cancer is the most common endocrine malignancy and over the past decades has shown the fastest increasing incidence of all malignancies. This cancer has a detrimental impact on a patients' quality of life (QoL), not very well considered in general practice. In this paper we aimed to review the QoL of DTC patients who received high doses of 131I and had (or not) a supplementary treatment. Our review includes physical, mental and social well-being and emotional and physical discomfort. Quality of life is related to the diagnostic and therapeutic procedures which DTC patients still have to undergo. Nuclear medicine physicians can maintain or restore the highest achievable QoL of these patients based on guidelines as well as individualized patient centered practice.

Acknowledging gray areas: 2015 vs. 2009 American Thyroid Association differentiated thyroid cancer guidelines on ablating putatively low-intermediate-risk patients.

PURPOSE: Typically formulated by investigators from "world centres of excellence," differentiated thyroid carcinoma (DTC) management guidelines may have more limited applicability in settings of less expert care and fewer resources. Arguably the world's leading DTC guidelines are those of the American Thyroid Association, revised in 2009 ("ATA 2009") and 2015 ("ATA 2015"). To further explore the issue of "real-world applicability" of DTC guidelines, we retrospectively compared indications for ablation using ATA 2015 versus ATA 2009 in a two-centre cohort of ablated T1-2, M0 DTC patients (N = 336). Based on TNM status and histology, these patients were low-intermediate risk, but many ultimately had other characteristics suggesting elevated or uncertain risk. METHODS: Working by consensus, two experienced nuclear medicine physicians considered patient and treatment characteristics to classify each case as having "no indication," a "possible indication," or a "clear indication" for ablation according to ATA 2009 or ATA 2015. The physicians also identified reasons for classification changes between ATA 2015 versus ATA 2009. Classification was unblinded, but the physicians had cared for only 138/336 patients, and the charts encompassed September 2010-October 2013, several years before the classification was performed. RESULTS: One hundred of 336 patients (29.8 %) changed classification regarding indication for ablation using ATA 2015 versus ATA 2009. Most reclassified patients (70/100) moved from "no indication" or "clear indication" to "possible indication." Reflecting this phenomenon, "possible indication" became the largest category according to the ATA 2015 classification (141/336, 42.0 %, versus 96/336, 28.6 %, according to ATA 2009). Many reclassifications were attributable to multiple clinicopathological characteristics, most commonly, stimulated thyroglobulin or anti-thyroglobulin antibody levels, multifocality, bilateral involvement, or capsular/nodal invasion. CONCLUSIONS: Regarding indications for ablation, ATA 2015 appears to better "acknowledge grey areas," i.e., patients with ambiguous or unavailable data requiring individualised, nuanced decision-making, than does ATA 2009.

[Radiation treatment of head and neck carcinomas as a risk factor for thyroid carcinomas].

OBJECTIVE: Cancer of the thyroid is a relatively rare malignant neoplasm with an increasing incidence in the last decades. Ionizing radiation is the best documented risk factor for thyroid malignant neoplasms, in current medical literature. An increase in the global annual per caput effective radiation dose has been described, partly as a result of medical exposure. External beam radiation therapy of the head and neck region has also been attributed. Thyroid tissue is particularly vulnerable to the carcinogenic effects of ionizing radiation because of its anatomical position and radiosensitivity. We review the relationship between external beam radiotherapy and secondary thyroid cancer and of factors influencing this correlation. Since 1950 this causal relationship has been confirmed by numerous researchers. The role of the primary disease, the administrated radiation dose, the irradiation field, sex, age and genetic background and also the time interval between radiation and the onset of thyroid cancer are the main factors that have been studied in medical literature. Developments in the field of radiotherapy, recent findings on the relationship between head and neck carcinomas and thyroid carcinomas and interactions between confounding factors, raise the need for further study on this subject.