Radioiodine versus radiofrequency ablation to treat autonomously functioning thyroid nodules: a systematic review and comparative meta-analysis.

PURPOSE: Radioiodine (RAI) is a well-established first-line therapy for autonomously functioning thyroid nodules (AFTN). Radiofrequency ablation (RFA) is a minimally invasive procedure that has been proposed as an alternative treatment option for hyperthyroidism caused by AFTN. Although RFA has been shown to be useful for reducing nodule volume and improving TSH levels in AFTN, no comprehensive comparative clinical studies have been proposed to evaluate the overall response to RFA treatment. The aim of this comparative systematic review and meta-analysis was to evaluate the response of RAI and RFA treatments in AFTN. METHODS: A systematic search strategy was applied in PubMed, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov until July 2023 without time or language restrictions. Studies investigating the response to RAI and/or RFA treatment in AFTN patients 6 and/or 12 months after treatment were included. The risk of bias was assessed based on the study design. Random-effect models were used for the meta-analysis. RESULTS: Twenty-three articles (28 reports) met the inclusion criteria and were included in the study. Overall, RAI therapy was found to have a significantly higher treatment response (94%) than RFA (59%), although the volume of AFTNs was reduced to a similar extent. In the direct comparison (n = 3 studies), RFA showed a higher risk of non-response than RAI (RR, 1.24; 95% CI, 0.94-1.63; z = 1.55; p = 0.12). CONCLUSIONS: Our results demonstrate the superiority of RAI over RFA in terms of success rates and safety profile and confirm RAI as the first choice for the treatment of AFTNs.

Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series.

OBJECTIVES: An accurate prognostic assessment is pivotal to adequately inform and individualize follow-up and management of patients with differentiated thyroid cancer (DTC). We aimed to develop a predictive model for recurrent disease in DTC patients treated by surgery and 131I by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), administered 131I activities and post-therapy whole body scintigraphy (PT-WBS) were identified as potential predictors and put into regression algorithm (conditional inference tree, c-tree) to develop a risk stratification model for predicting persistent/recurrent disease over time. RESULTS: The PT-WBS pattern identified a partition of the population into two subgroups (PT-WBS positive or negative for distant metastases). Patients with distant metastases exhibited lower disease-free survival (either structural, DFS-SD, and biochemical, DFS-BD, disease) compared to those without metastases. Meanwhile, the latter were further stratified into three risk subgroups based on their Tg values. Notably, Tg values >63.1 ng/mL predicted a shorter survival time, with increased DFS-SD for Tg values <63.1 and <8.9 ng/mL, respectively. A comparable model was generated for biochemical disease (BD), albeit different DFS were predicted by slightly different Tg cutoff values (41.2 and 8.8 ng/mL) compared to DFS-SD. CONCLUSIONS: We developed a simple, accurate and reproducible decision tree model able to provide reliable information on the probability of structurally and/or biochemically persistent/relapsed DTC after a TTA. In turn, the provided information is highly relevant to refine the initial risk stratification, identify patients at higher risk of reduced structural and biochemical DFS, and modulate additional therapies and the relative follow-up.

Free thyroxine measurement in clinical practice: how to optimize indications, analytical procedures, and interpretation criteria while waiting for global standardization.

Thyroid dysfunctions are among the most common endocrine disorders and accurate biochemical testing is needed to confirm or rule out a diagnosis. Notably, true hyperthyroidism and hypothyroidism in the setting of a normal thyroid-stimulating hormone level are highly unlikely, making the assessment of free thyroxine (FT4) inappropriate in most new cases. However, FT4 measurement is integral in both the diagnosis and management of relevant central dysfunctions (central hypothyroidism and central hyperthyroidism) as well as for monitoring therapy in hyperthyroid patients treated with anti-thyroid drugs or radioiodine. In such settings, accurate FT4 quantification is required. Global standardization will improve the comparability of the results across laboratories and allow the development of common clinical decision limits in evidence-based guidelines. The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests has undertaken FT4 immunoassay method comparison and recalibration studies and developed a reference measurement procedure that is currently being validated. However, technical and implementation challenges, including the establishment of different clinical decision limits for distinct patient groups, still remain. Accordingly, different assays and reference values cannot be interchanged. Two-way communication between the laboratory and clinical specialists is pivotal to properly select a reliable FT4 assay, establish reference intervals, investigate discordant results, and monitor the analytical and clinical performance of the method over time.

Long-term predictive value of highly sensitive thyroglobulin measurement.

OBJECTIVE: To examine the predictive value of unremarkable nonstimulated highly sensitive thyroglobulin (hsTg) measurement with regard to the results of stimulated thyroglobulin (Tg) measurement, diagnostic whole-body scintigraphy, recurrence and differentiated thyroid cancer (DTC)-related death. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed the data of all 461 (410 without anti-Tg-antibodies [TgAbs], 51 with) DTC patients who were referred to our department for treatment and follow-up care of differentiated thyroid cancer from 2004 onwards, and in whom at least one posttreatment Tg value was measured in our hospital at least 3 months after I-131 ablation. RESULTS: In the group of TgAb-negative patients, 2.0% of patients with an unstimulated Tg < 0.1 ng/ml showed a stimulated Tg ≥ 1.0 ng/ml, whereas this happened in 77.6% with an unstimulated Tg ≥ 0.1 but <1.0 ng/ml. An unstimulated hsTg ≥ 0.1 ng/ml had a sensitivity specificity positive and negative predictive value of 90.0%, 94.1%, 77.6% and 97.6%, respectively, for a stimulated Tg ≥ 1.0 ng/ml. In TgAb-positive patients, this was 75%, 97%, 75% and 97%, respectively. An unstimulated Tg ≥ 0.1 ng/ml did not significantly discriminate with regard to the risk of DTC-related death (p = .06), but ≥1.0 ng/ml did (p = .012), as did a stimulated Tg ≥ 1.0 ng/ml (p = .029). Excluding patients with distant metastases at diagnosis nullifies this significance. CONCLUSION: Except for patients with distant metastases, both TgAb negative and TgAb positive patients with an undetectable nonstimulated hsTg measurement have a very good prognosis. The high net present value of unstimulated hsTg testing means that further diagnostic procedures can be omitted in such patients.

Prognostic role of early prostate specific antigen changes after [177 Lu]Lu-PSMA radioligand therapy of metastasized prostate cancer: A meta-analysis.

BACKGROUND: Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [177 Lu]Lu-prostate-specific membrane antigen (PSMA) is an emerging treatment for metastasized mCRPC and its efficacy is assessed not only but also by prostate specific antigen (PSA) measurement after 12 weeks or more after treatment. Our aim was to evaluate the role of early PSA measurement after RLT in predicting overall survival (OS) of mCRPC patients. METHODS: A systematic search on PubMed, Web Of Science and Scopus was performed from January to December 2022. PRISMA guidelines for prognostic studies was adopted. Risk of bias was assessed using quality of prognostic studies (QUIPS). RESULTS: Twelve studies at low-intermediate risk of bias, were included in the meta-analysis (1646 patients, mean age 70 years). About 50% of patients showed a PSA decline after 1-2 of [177 Lu]Lu-PSMA, and more than 30% reported a PSA decline ≥50%. The median OS range for patients with any PSA decline was 13-20 months, while for patients with stable or increased PSA, the median OS fell to 6-12 months. The OS rate for a PSA decline after the one-two [177 Lu]Lu-PSMA cycles was 0.39 (95% CI: 0.31-0.50), while OS for a PSA decline ≥50% was 0.69 (95% CI: 0.57-0.83). CONCLUSIONS: A PSA decline is observed in almost 50% of mCRPC patients after 1-2 [177 Lu]Lu-PSMA cycles, with a significantly longer OS compared to stable or increased PSA levels, respectively. Accordingly, any PSA decline after 1-2 cycles of therapy should be regarded as a favourable prognostic factor for OS.

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.

EANM enabling guide: how to improve the accessibility of clinical dosimetry.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

Postoperative thyroglobulin as a yard-stick for radioiodine therapy: decision tree analysis in a European multicenter series of 1317 patients with differentiated thyroid cancer.

PURPOSE: An accurate postoperative assessment is pivotal to inform postoperative 131I treatment in patients with differentiated thyroid cancer (DTC). We developed a predictive model for post-treatment whole-body scintigraphy (PT-WBS) results (as a proxy for persistent disease) by adopting a decision tree model. METHODS: Age, sex, histology, T stage, N stage, risk classes, remnant estimation, TSH, and Tg were identified as potential predictors and were put into regression algorithm (conditional inference tree, ctree) to develop a risk stratification model for predicting the presence of metastases in PT-WBS. RESULTS: The lymph node (N) stage identified a partition of the population into two subgroups (N-positive vs N-negative). Among N-positive patients, a Tg value > 23.3 ng/mL conferred a 83% probability to have metastatic disease compared to those with lower Tg values. Additionally, N-negative patients were further substratified in three subgroups with different risk rates according to their Tg values. The model remained stable and reproducible in the iterative process of cross validation. CONCLUSIONS: We developed a simple and robust decision tree model able to provide reliable informations on the probability of persistent/metastatic DTC after surgery. These information may guide post-surgery 131I administration and select patients requiring curative rather than adjuvant 131I therapy schedules.

Evolution of thyroid cancer biomarkers: from laboratory test to patients' clinical management.

Over the past three decades, laboratory medicine has significantly evolved thanks to technological advances made possible by new materials and evidence. Clinicians' ongoing requests for powerful, rapid, and minimally invasive tests has led manufacturers to develop rapid, accurate, and sensitive tests that can increase diagnostic accuracy and improve follow-up, bringing laboratory medicine ever closer to personalized medicine. The aim of this study was to critically review the main problems of the current Tg and CT biomarkers for the diagnosis/monitoring of DTC and MTC, respectively, and to identify the advantages and challenges of using the new laboratory biomarkers in the clinical management of patients with differentiated and medullary thyroid cancer. Insufficient harmonization of Tg and CT assays and lack of interchangeability of laboratory results and cutoff values pose challenges for comparability and standardization of procedures and methods. New diagnostic and monitoring approaches such as PCT or the Tg doubling time have proven to be effective. Close collaboration between clinicians and laboratory specialists remains essential to translate the advantages and limitations of current assays into appropriate clinical interpretation criteria. Over the years, the journal Clinical Chemistry and Laboratory Medicine (CCLM) has taken many steps to develop advanced research and technology in the diagnosis and monitoring of tumor cancer and to help clinicians translate it into clinical practice.

BRAF-AXL-PD-L1 Signaling Axis as a Possible Biological Marker for RAI Treatment in the Thyroid Cancer ATA Intermediate Risk Category.

The use of radioiodine therapy (RIT) is debated in intermediate-risk differentiated thyroid cancer (DTC) patients. The understanding of the molecular mechanisms involved in the pathogenesis of DTC can be useful to refine patient selection for RIT. We analyzed the mutational status of BRAF, RAS, TERT, PIK3 and RET, and the expression of PD-L1 (as a CPS score), the NIS and AXL genes and the tumor-infiltrating lymphocytes (TIL, as the CD4/CD8 ratio), in the tumor tissue in a cohort of forty-six ATA intermediate-risk patients, homogeneously treated with surgery and RIT. We found a significant correlation between BRAF mutations and a less than excellent (LER, according to 2015 ATA classification) response to RIT treatment (p = 0.001), higher expression of the AXL gene (p = 0.007), lower expression of NIS (p = 0.045) and higher expression of PD-L1 (p = 0.004). Moreover, the LER patient group had a significantly higher level of AXL (p = 0.0003), a lower level of NIS (p = 0.0004) and a higher PD-L1 level (p = 0.0001) in comparison to patients having an excellent response to RIT. We also found a significant direct correlation between the AXL level and PD-L1 expression (p < 0.0001) and a significant inverse correlation between AXL and NIS expression and TILs (p = 0.0009 and p = 0.028, respectively). These data suggest that BRAF mutations and AXL expression are involved in LER among DTC patients and in the higher expression of PD-L1 and CD8, becoming new possible biomarkers to personalize RIT in the ATA intermediate-risk group, as well as the use of higher radioiodine activity or other possible therapies.

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.

Joint EANM, SNMMI and IAEA enabling guide: how to set up a theranostics centre.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of existing and the establishment of new theranostics centres. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostics centres. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Generation and validation of a PET radiomics model that predicts survival in diffuse large B cell lymphoma treated with R-CHOP14: A SAKK 38/07 trial post-hoc analysis.

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression-free (PFS), cause-specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p < 0.001) and validation (AUC, 0.706; p < 0.001) sets. RS was significantly associated also with CSS and OS in testing (CSS: AUC, 0.721; p < 0.001; OS: AUC, 0.740; p < 0.001) and validation (CSS: AUC, 0.763; p < 0.0001; OS: AUC, 0.703; p = 0.004) sets. The RS allowed risk classification of patients with significantly different PFS, CSS, and OS in both cohorts showing better predictive accuracy respect to clinical international indices. PET-derived radiomics may improve the prediction of outcome in DLBCL patients.

Functional and molecular thyroid imaging.

Nuclear medicine methods were introduced in the 1940s for thyroid disease diagnosis and therapy. They is still a crucial part of thyroid nodules work-up. Thyroid imaging with iodine or iodine-analog isotopes is widely employed in patients with thyrotoxicosis and remains the only examination able to prove the presence of autonomously functioning thyroid tissue, which excludes malignancy with a high probability. In addition, technetium-99m-methoxyisobutylisonitrile ([99mTc]Tc-MIBI) scintigraphy and positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxy-d-glucose ([18F]FDG) are able to avoid unnecessary surgical procedures for cytologically inconclusive thyroid nodules, as confirmed by meta-analysis and cost-effectiveness studies. All considered thyroid molecular imaging allows functional characterization of different thyroid diseases, even before clinical symptoms become manifest, and remains integral to the management of such conditions. This paper summarizes main concepts of thyroid scintigraphy and its clinical use. In addition, it elaborates development of thyroid scintigraphy, as well as thyroid molecular imaging in patients with thyroid nodules and thyrotoxicosis.

An essential practice summary of the new EANM guidelines for parathyroid imaging.

Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.

Is thyroglobulin a reliable biomarker of differentiated thyroid cancer in patients treated by lobectomy? A systematic review and meta-analysis.

OBJECTIVES: The prognostic role of thyroglobulin in predicting recurrence in differentiated thyroid cancer (DTC) patients treated by lobectomy is controversial. This systematic review with meta-analysis aimed to update the current evidence deepening the reliability of circulating thyroglobulin in assessing the early response and in predictive recurrence. METHODS: The methodology was registered in the PROSPERO database under the protocol number CRD42021288189. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from September to November 2021 without time and language restrictions. The literature search strategy was based on the following keywords: Thyroglobulin AND (Lobectomy OR Hemithyroidectomy). RESULTS: After screening 273 articles, seven studies were included in the systematic review, and only six of them were included in the meta-analysis for a total of 2,455 patients. Circulating thyroglobulin was found non-reliable in assessing early response and predicting recurrence in patients with hemithyroidectomy, especially those with a low initial ATA classification. CONCLUSIONS: Our study does not support serum thyroglobulin levels for monitoring patients with low-risk DTC treated with lobectomy, and weak evidence supports its role for intermediate- or high-risk patients. Studies with longer follow-up, different study designs, and stringent inclusion/exclusion criteria are needed to evaluate the role of thyroglobulin in recurrence prediction.

CT evaluation of lung infiltrates in the two months preceding the Coronavirus disease 19 pandemic in Canton Ticino (Switzerland): were there suspicious cases before the official first case?

PURPOSE: The main objective of this study was to assess the presence of pulmonary infiltrates with computed tomography (CT) appearance compatible with infection by coronavirus disease 2019 (COVID-19), in Canton Ticino in the 2 months preceding the first official case. Secondary aims were to compare the classification of infiltrates in the same time frame in 2020 and 2019; to compare the number of chest CT scans in the same period; to search for pathological confirmation of the virus. MATERIALS AND METHODS: Chest CT scans performed between January 1 and February 24 in 2019 and 2020 were collected and classified by COVID-19 Reporting and Data System (CO-RADS). Pathological presence of the virus was searched for when appropriate material was available. RESULTS: The final cohort included 881 patients. Among the CO-RADS 3 and 4 categories, 30 patients had pneumonitis of unknown etiology. Pathological specimens were available in six patients but they were negative for COVID-19. CONCLUSION: Before the first official case of COVID-19 infection, in Canton Ticino there were about 30 cases of pneumonitis of uncertain origin, with CT appearance compatible with infection by COVID-19, but with no confirmation of the disease. The number of chest CT scans in the first two months of 2020 was > 12% compared to 2019.

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.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

AIM: Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12 months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. MATERIAL AND METHODS: We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2 days after RaIT (late-stimulated Tg). The early response assessment was done 12 months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. RESULTS: Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874) ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. CONCLUSION: Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

The EANM practice guidelines for parathyroid imaging.

INTRODUCTION: Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration. METHODS: Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT. CONCLUSION: These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.