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.

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.

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.

Pre-Treatment and Post-Treatment I-131 Imaging in Differentiated Thyroid Carcinoma.

Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment.

Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

PET/CT Variants and Pitfalls in Head and Neck Cancers Including Thyroid Cancer.

PET/CT imaging is a dual-modality diagnostic technology that merges metabolic and structural imaging. There are several currently available radiotracers, but 18F-FDG is the most commonly utilized due to its widespread availability. 18F-FDG PET/CT is a cornerstone of head and neck squamous cell carcinoma imaging. 68Ga-DOTA-TOC is another widely used radiotracer. It allows for whole-body imaging of cellular somatostatin receptors, commonly expressed by neuroendocrine tumors and is the standard of reference for the characterization and staging of neuroendocrine tumors. The normal biodistribution of these PET radiotracers as well as the technical aspects of image acquisition and inadequate patient preparation affect the quality of PET/CT imaging. In addition, normal variants, artifacts and incidental findings may impede accurate image interpretation and can potentially lead to misdiagnosis. In order to correctly interpret PET/CT imaging, it is necessary to have a comprehensive knowledge of the normal anatomy of the head and neck and to be cognizant of potential imaging pitfalls. The interpreter must be familiar with benign conditions which may accumulate radiotracer potentially mimicking neoplastic processes and also be aware of malignancies which can demonstrate low radiotracer uptake. Appropriate use of structural imaging with either CT, MR or ultrasound can serve a complimentary role in several head and neck pathologies including local tumor staging, detection of bone marrow involvement or perineural spread, and classification of thyroid nodules. It is important to be aware of the role of these complementary modalities to maximize diagnostic accuracy and patient outcomes. The purpose of this article is to outline the basic principles of PET/CT imaging, with a focus on 18F-FDG PET/CT and 68Ga-DOTA PET/CT. Basic physiology, variant imaging appearances and potential pitfalls of image interpretation are presented within the context of common use cases of PET technology in patients with head and neck cancers and other pathologies, benign and malignant.

MRI versus ¹³¹I whole-body scintigraphy for the detection of lymph node recurrences in differentiated thyroid carcinoma.

OBJECTIVE: The aim of this study was to compare the clinical usefulness of MRI and radioiodine (¹³¹I) whole-body scintigraphy for the detection of lymph node metastases in differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: After surgery and ¹³¹I therapy, 40 patients with DTC underwent ¹³¹I whole-body scintigraphy and MRI. Each patient was clinically suspected of having or already had evidence of nodal recurrences (confirmed by laboratory studies, cytologic analysis, or whole-body scintigraphy). Planar whole-body scintigraphy was done after administration of 111 MBq of ¹³¹I, and MRI was done using spin-echo T1- and T2-weighted imaging, T1-weighted spin-echo imaging with fat suppression, and STIR sequences. RESULTS: MRI detected nodal metastases as partly or entirely cystic and as heterogeneously enhanced on contrast-enhanced T1-weighted images. Hyperintense cystic areas appeared on T1- and T2-weighted images and STIR sequences in 57% of cases. Nodal metastases showed extracapsular spread in 24% of patients. MRI results were true-positive in 76%, true-negative in 90%, false-negative in 24%, and false-positive in 11% of cases, whereas ¹³¹I whole-body scintigraphy results were true-positive in 71%, true-negative in 91%, and false-negative in 29% of cases. There were no false-positive results of ¹³¹I whole-body scintigraphy. False-negative whole-body scintigraphy was induced by tumor dedifferentiation. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MRI were 76.2%, 89.5%, 82.5%, 88.9%, and 77.3%, respectively, and the corresponding values for ¹³¹I whole-body scintigraphy were 71.4%, 100%, 85%, 100%, and 76%, respectively. CONCLUSION: Whole-body scintigraphy is more specific than MRI in the detection of nodal metastases in patients with DTC. The principal value of MRI is in non-iodine-avid recurrences and in evaluation of mediastinal foci.

Aminosilanized flower-structured superparamagnetic iron oxide nanoparticles coupled to 131I-labeled CC49 antibody for combined radionuclide and hyperthermia therapy of cancer.

Combined radionuclide therapy with magnetic nanoparticles-mediated hyperthermia has been under research focus as a promising tumor therapy approach. The objective of this study was to investigate the potential of 131I-radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) prepared as the ~40 nm flower-shaped structures with excellent heating efficiency (specific absorption rate at H0 = 15.9 kA∙m-1 and resonant frequency of 252 kHz was 123.1 W∙g-1) for nano-brachytherapy of tumors. 131I-radiolabeled CC49 antibody attached to SPIONs via reactive groups of 3-aminopropyltriethoxysilane (APTES) provided specificity and long-lasting localized retention after their intratumoral application into LS174T human colon adenocarcinoma xenografts in NOD-SCID mice. The results demonstrate feasibility and effectiveness of magnetic hyperthermia (HT), radionuclide therapy (RT) and their combination (HT + RT) in treating cancer in xenograft models. Combined therapy approach induced a significant (p < 0.01) tumor growth suppression in comparison to untreated groups presented by the tumor volume inhibitory rate (TVIR): 54.38%, 68.77%, 73.00% for HT, RT and HT + RT, respectively in comparison to untreated group and 48.31%, 64,62% and 69,41%, respectively, for the SPIONs-only injected group. Histopathology analysis proved the necrosis and apoptosis in treated tumors without general toxicity. Obtained data support the idea that nano-brachytherapy combined with hyperthermia is a promising approach for effective cancer treatment.

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey.

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case-control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial "misdiagnosis."

Differentiated thyroid carcinoma with distant metastases: probability of survival and its predicting factors.

The purpose was to analyze survival and its predicting factors in differentiated thyroid carcinoma (DTC) patients with distant metastases (M1). Radioiodine ((131)I) therapy was performed in 363 DTC patients from 1977 to 2000. Among 75 patients, 44 patients had M1 at the time of initial therapy and 31 patients had M1, which developed during the follow up. The probability of survival and its predicting factors were tested by Kaplan-Meier's method. Seventy five DTC patients with M1 included 49 (65.3%) women and 26 (34.7%) men; 30 (40%) patients were < 45 years old and 45 (60%) patients were >or= 45 years old (range 8-70 years; mean age = 45.5 years); 52 papillary carcinomas, 22 follicular carcinomas, and one inconclusive finding. Probability of survival after appearance of M1 was 60.7% at 5 years, 51.2% at 10, and 38.4% at 15 and 20 years. Some predicting factors showed significant influence on the survival: age (p = 0.0001), histological type (p = 0.0138), and initial therapy (p = 0.0351), while gender had no influence (p = 0.2046). We can conclude that patients' age, histopathology of the tumor, and initial therapy significantly influence the survival. Longer survival of DTC patients with M1 could be achieved by adequate surgery followed by 131I therapy.

18F-fluorideoxyglucose positron emission tomography/computed tomography imaging: artifacts and pitfalls.

"F-fluorodeoxyglucose, being a radiolabeled glucose analogue, is a marker of glucose metabolism indicator. Since glucose uptake is increased in malignant tumors, its major application is in oncology. However, an increased 18F-fluorodeoxyglucose uptake is found in various benign tumors, granulomatous diseases, tuberculosis, inflammation, infection. A healing process may be interpreted as a false positive finding. In contrast, some types of renal cell cancers and lymphomas, neuroendocrine tumors, colonic mucinous adenocarcinomata, hepatocellular carcinomas, prostate cancer, and carcinoid tumors have low "F-fluorodeoxyglucose avidity which may give a misleading false negative result. In addition, an increased "F-fluorodeoxyglucose uptake in the bone marrow may be seen in oncologycal patients following various types of therapy. Besides the advantages of hybrid positron emission tomography-computed tomography imaging, this dual-modality scanning may produce their own specific artifacts due to different causes, such as metallic implants, respiratory motion, contrast medium and truncation. Proper patient preparation is required to minimize the potential artifactual uptake patterns that make reporting difficult. It is important to learn about proper quality control, imaging and reconstruction and to be familiar with potential artifacts and, pitfalls for the accurate interpretation of "F-fluorodeoxyglucose positron emission tomography-computed tomography.