Neck lymph node metastasis detection in patients with differentiated thyroid carcinoma (DTC) in long-term follow-up: a 131I-SPECT/CT study.

BACKGROUND: The identification of neck lymph node (LN) metastases represents a very important issue in the management of patients with differentiated thyroid carcinoma (DTC). To this purpose, in the present study, we used 131I-SPECT/CT as a diagnostic imaging procedure. METHODS: A consecutive series of 224 DTC patients with ascertained neck radioiodine-avid foci at 131I-SPECT/CT during long-term follow-up was evaluated. All patients had already undergone total thyroidectomy and radioiodine therapy and had been classified as follows: 62 at high risk (H), 64 at low risk (L) and 98 at very low risk (VL). 131I-Whole body scan (WBS) followed by SPECT/CT was performed in all cases. RESULTS: In the 224 patients, 449 neck iodine avid foci were ascertained at SPECT/CT, while 322 were evidenced at WBS in 165/224 patients. WBS classified as residues 263/322 foci and as unclear 59/322 foci; among the former foci SPECT/CT correctly characterized 8 LN metastases and 3 physiologic uptakes and among the latter, it pinpointed 26 LN metastases, 18 residues, and 15 physiologic uptakes. SPECT/CT also classified 127 foci occult at WBS as 59 LN metastases and 68 residues. Globally, SPECT/CT identified 93 LN metastases in 59 patients (26 H, 20 L, 13 VL), while WBS evidenced 34 in 25 cases. All 13 VL patients, T1aN0M0, 5 of whom with LN near sub-mandibular glands, had thyroglobulin undetectable or < 2.5 ng/ml. Globally, SPECT/CT obtained an incremental value than WBS in 45.5% of patients, a more correct patient classification changing therapeutic approach in 30.3% of cases and identified WBS false-positive findings in 8% of cases. CONCLUSIONS: 131I-SPECT/CT proved to correctly detect and characterize neck LN metastases in DTC patients in long-term follow-up, improving the performance of planar WBS. SPECT/CT routine use is thus suggested; its role is particularly relevant in patients with WBS inconclusive, VL, T1aN0M0 and with undetectable or very low thyroglobulin levels.

Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up.

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28-5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised.

The Role of Risk Factors for the Progression of Patients with T1b-T2 Papillary Thyroid Carcinoma (PC) during Long-Term Follow-Up.

Background/Objectives: Recurrence prediction for patients with PC and tumor sizes ranging between 1 and 4 cm, classified as T1b and T2, remains a controversial problem. We evaluated which risk factors, identified during the primary tumor surgery, might play a prognostic role in predicting disease progression. Methods: We retrospectively enrolled 363 patients with classic PC who were in follow-up (207 T1b, 156 T2), with tissue risk factors at surgery in 209/363 cases. In all cases, an 131I-whole-body scan, SPECT/CT, and US were employed to detect any metastases during follow-up, and histology was used to confirm lesions. In the absence of surgery, metastases were validated by radioisotopic and radiologic procedures, eventually culminating in a needle biopsy and sequential thyroglobulin changes. Results: Metastases occurred in 61/363 (16.8%) patients (24 T1b, 37 T2). In 50/61 cases, the following risk factors were identified: minimal extrathyroid tumor extension (mETE) alone in 12/50 patients, neck lymph node (LN) metastases in 8/50 cases, and multifocality/multicentricity (M/M) in 6/50 cases. In the remaining 24/50 cases, the risk factors were associated with each other. From a Cox regression multivariate analysis, metastasis development was significantly (p < 0.001) influenced by only mETE and LN metastases, with a shorter disease-free survival (log-rank test). Conclusions: The current study proves that mETE and neck LN metastases are associated with aggressive PC. While LN metastasis' role is known, mETE's role is still being debated, and was removed by the AJCC's eighth edition because it was considered to not be associated with an unfavorable prognosis. However, this interpretation is not supported by the present study and, according to comparable studies, we suggest a revision of the mETE classification be considered in the next AJCC edition.

Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma: A Follow-Up Study in Patients with Absence of Aggressive Risk Factors at the Surgery of the Primary Tumor.

Hashimoto's thyroiditis (HT) is often associated with papillary thyroid carcinoma (PC); it is still a matter of controversy whether the behavior of carcinoma is more aggressive or not. During the follow-up, we retrospectively enrolled 97 patients with PC/HT after thyroidectomy without risk factors at the surgery of the primary tumor, such as multifocality/multicentricity, extrathyroid tumor extension, vascular invasion, neck and distant metastases, and aggressive histological variants. HT diagnosis was confirmed by histology and serum thyroid antibodies. Tumor size was ≤10 mm in 64 cases (microcarcinomas); 206 matched PC patients after thyroidectomy without HT and risk factors were enrolled as controls, totaling 122 microcarcinomas. During follow-up, metastases occurred in 15/97 (15.5%) PC/HT cases, eight microcarcinomas, and in 16/206 (7.8%) without HT, eight microcarcinomas (p = 0.04). Considering both PC/HT and PC patients without HT who developed metastases, univariate analysis showed an increased risk of metastases in patients with HT coexistence, OR: 2.17 (95% CI 1.03-4.60) p = 0.043. Disease-free survival (DFS) was significantly (p = 0.0253) shorter in PC/HT than in the controls. The present study seems to demonstrate that HT is not a cancer protective factor in PC patients given the less favorable outcomes and significantly shorter DFS. HT may also represent an independent recurrence predictor without other risk factors.

Metastatic differentiated thyroid cancer with negative serum stimulated Tg but positive post-therapeutic 131I-SPECT/CT scintigraphy: a single-center retrospective study.

PURPOSE: This study aimed to describe the characteristics of patients with metastatic differentiated thyroid carcinoma (DTC) who had positive 131I-scintigraphy but negative stimulated thyroglobulin (sTg), and to evaluate their short-term response to radioiodine therapy (RAI). METHODS: A total of 2250 consecutive postoperative DTC patients, who underwent RAI treatment from July 2019 to June 2022, were analyzed retrospectively. The target group was defined as stimulated Tg < 2 ng/mL with TgAb < 100 IU/mL but with post-therapeutic 131I-SPECT/CT metastases. The characteristics of these patients were analyzed and the metastatic profiles were compared with TgAb positive or sTg positive ones. A cross-sectional efficacy was evaluated 6-12 months after the RAI therapy and the treatment course until the end of the study was recorded. RESULTS: 105 (4.67%) DTC patients were post-therapeutic 131I-SPECT/CT positive and sTg negative (target group). Metastatic profiles were found significant differences between sTg negative and sTg positive ones (P < 0.001). Excellent response (ER) was achieved in 72.4% of the target group between 6-12 months of cross-sectional efficacy assessment, compared with only 12.8% in sTg positive ones (P < 0.001). The majority of the target group didn't require aggressive treatment in short-term follow-up compared with sTg positive group (P < 0.001). CONCLUSION: The percentage of DTCs with negative sTg but positive post-therapeutic 131I-SPECT/CT was relatively low, but still significant. Moreover, the majority of these patients showed an ER to RAI and may not require the next course of therapy. Long-term follow-up is still necessary to assess recurrence and adapt surveillance in these patients.

A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves' Disease.

Whether papillary carcinoma (PC) behavior is more aggressive in Graves' disease (GD) patients than PC cases without GD is controversial. We retrospectively enrolled 33 thyroidectomized PC/GD patients during long-term follow-up, 23/33 without risk factors at surgery, and 18/33 microcarcinomas; 312 PC euthyroid-matched patients without risk factors served as controls. A total of 14/33 (42.4%) PC/GD patients, 4 with and 10 without risk factors at diagnosis, 6 with microcarcinoma, underwent metastases during follow-up. In controls, metastases in 21/312 (6.7%) were ascertained. Considering 10/23 PC/GD patients and 21/312 controls without risk factors who developed metastases, univariate analysis showed that there was an increased risk of metastasis appearance for PC/GD cases (p < 0.001). Disease-free survival (DFS) was significantly (p < 0.0001, log-rank test) shorter in PC/GD patients than in controls. Significantly more elevated aggressiveness in 6/18 PC/GD patients with microcarcinoma than in controls was also ascertained with shorter DFS. Thus, in the present study, PC/GD had aggressive behavior during follow-up also when carcinoma characteristics were favorable and some cases were microcarcinomas. GD and non-GD patient comparison in the cases without risk factors at diagnosis showed an increased risk to develop metastases in GD during follow-up, suggesting that GD alone might be a tumor aggressiveness predictive factor in these cases.

The Diagnostic Usefulness of 131I-SPECT/CT at Both Radioiodine Ablation and during Long-Term Follow-Up in Patients Thyroidectomized for Differentiated Thyroid Carcinoma: Analysis of Tissue Risk Factors Ascertained at Surgery and Correlated with Metastasis Appearance.

131I Single-photon emission computerized tomography/computerized tomography (SPECT/CT) in the management of patients thyroidectomized for differentiated thyroid carcinoma (DTC) was further investigated. Retrospectively, 106 consecutive DTC patients were enrolled at the first radioiodine ablation, 24 at high risk (H), 61 at low risk (L) and 21 at very low risk (VL). 131I whole-body scan (WBS) and SPECT/CT were performed after therapeutic doses using a hybrid dual-head gamma camera. At ablation, SPECT/CT correctly classified 49 metastases in 17/106 patients with a significantly (p < 0.001) more elevated number than WBS which evidenced 32/49 foci in 13/17 cases. In this case, 86/106 patients could be monitored in the follow-up including 13/17 cases with metastases already at post-therapeutic scans. SPECT/CT after radioiodine diagnostic doses more correctly than WBS ascertained disease progression in 4/13 patients, stable disease in other 4/13 cases and disease improvement in the remaining 5/13 cases. Further 13/86 patients with only residues at post-therapeutic scans showed at SPECT/CT 16 neck lymph node (LN) metastases, three unclear and 13 occult at WBS. Significant involvement of some tissue risk factors with metastasis appearance was observed, such as minimal extrathyroid tumor extension and neck LN metastases. These risk factors should be carefully considered in DTC patient follow-up where 131I-SPECT/CT routinely use is suggested as a support tool of WBS.

Thyroid Cancer Radiotheragnostics: the case for activity adjusted 131I therapy.

Radiotheragnostics represents the systematic integration of diagnostic imaging and therapeutics using radionuclides targeting specific characteristics of tumor biology. Radioiodine (131I) is the classic radiotheragnostic agent used for the diagnosis and treatment of differentiated thyroid cancer (DTC) based on sodium-iodine symporter expression in normal and neoplastic thyroid tissue. Application of radiotheragnostics principles in thyroid cancer involves using pre-ablation diagnostic scans (Dx Scans) for detection of iodine-avid regional and distant metastatic disease and patient-individualized targeted 131I therapy with goal of maximizing the benefits of the first therapeutic 131I administration. Clinically available nuclear medicine imaging technology has significantly evolved over the past 10 years with the introduction of hybrid SPECT/CT and PET/CT systems, as well as advances in iterative image reconstruction with modeling of image degrading physical factors. This progress makes possible the acquisition of accurate diagnostic radioiodine scintigraphy capable of identifying regional and distant metastatic disease, which can be used for 131I treatment planning and delivery of activity adjusted 131I therapy for achieving intended treatment goals (e.g. remnant ablation, adjuvant 131 I treatment and targeted 131-I treatment). The overarching aim of thyroid cancer radiotheragnostics is to optimize the balance between 131I therapeutic efficacy and potential side-effects on non-target tissues.

Role of Diagnostic 131I SPECT/CT in Long-Term Follow-up of Patients with Papillary Thyroid Microcarcinoma.

Papillary thyroid microcarcinoma (PTMC) usually has a favorable prognosis but can also be aggressive, with neck and distant metastases. We evaluated the diagnostic role of 131I SPECT/CT in detecting metastases in PTMC patients during long-term follow-up and whether the procedure should be included in the current diagnostic protocol. Methods: We retrospectively studied 351 consecutive PTMC patients who had undergone thyroidectomy and radioiodine therapy; 21 were at high risk, 94 at low risk, and 236 at very low risk. During follow-up, the patients underwent diagnostic 131I whole-body scanning (WBS) followed by SPECT/CT. Results: WBS found 248 radioiodine-avid foci in 126 patients, and SPECT/CT found 298 in 139 patients, confirming all foci found on WBS. SPECT/CT also correctly classified 76 of the avid foci as unclear or wrongly classified on WBS. Globally, SPECT/CT detected and correctly classified 64 neoplastic lesions in 27 of 30 patients with metastases, and WBS evidenced 39 of 64 lesions, 28 of which were unclear or wrongly classified, in 16 of the 30 patients. Nineteen of 27 patients, including 13 at very low risk, had only neck metastases, 9 of 19 being T1aN0M0 with an undetectable thyroglobulin level. Three of 27 patients, including 1 at very low risk, had only distant metastases with an undetectable or very low thyroglobulin level. Five of 27 patients had neck and distant metastases with a thyroglobulin level <2.5 ng/mL in 1 case, between 2.5 and 10 in 3 cases, and >10 in the remaining case. SPECT/CT also reduced WBS false-positive results in 15 of 139 patients (10.8%). SPECT/CT had an incremental value over WBS in 38.1% of patients with positive findings and changed the classification and therapeutic management in 21.6%. Conclusion: Metastases occurred in 8.5% of patients during long-term follow-up. SPECT/CT performed better than WBS, particularly in patients at very low risk with inconclusive WBS results, a TNM stage of T1aN0M0, and an undetectable or very low level of thyroglobulin. Prolonged surveillance is justified in PTMC patients, and wider use of 131I SPECT/CT in the diagnostic protocol is suggested.

Quantitative Comparison of 124I PET/CT and 131I SPECT/CT Detectability.

UNLABELLED: Radioiodine therapy with (131)I is used for treatment of suspected recurrence of differentiated thyroid carcinoma. Pretherapeutic (124)I PET/CT with a low activity (~1% of (131)I activity) can be performed to determine whether uptake of (131)I, and thereby the desired therapeutic effect, may be expected. However, false-negative (124)I PET/CT results as compared with posttherapeutic (131)I SPECT/CT have been reported by several groups. The purpose of this study was to investigate whether the reported discrepancies may be ascribed to a difference in lesion detectability between (124)I PET/CT and (131)I SPECT/CT and, hence, whether the administered (124)I activity is sufficient to achieve equal detectability. METHODS: Phantom measurements were performed using the National Electrical Manufacturers Association 2007 image-quality phantom. As a measure of detectability, the contrast-to-noise ratio was calculated. The (124)I activity was expressed as the percentage of (131)I activity required to achieve the same contrast-to-noise ratio. This metric was defined as the detectability equivalence percentage (DEP). RESULTS: Because lower DEPs were obtained for smaller spheres, a relatively low (124)I activity was sufficient to achieve similar lesion detectability between (124)I PET/CT and (131)I SPECT/CT. DEP was 1.5%, 1.9%, 1.9%, 4.4%, 9.0%, and 16.2% for spheres with diameters of 10, 13, 17, 18, 25, and 37 mm, respectively, for attenuation- and scatter-corrected SPECT versus point-spread function (PSF) model-based and time-of-flight (TOF) PET. For no-PSF no-TOF PET, DEP was 3.6%, 2.1%, 3.5%, 7.8%, 15.1%, and 23.3%, respectively. CONCLUSION: A relatively low (124)I activity of 74 MBq (~1% of (131)I activity) is sufficient to achieve similar lesion detectability between (124)I PSF TOF PET/CT and (131)I SPECT/CT for small spheres (≤10 mm), since the reported DEPs are close to 1%. False-negative (124)I PET/CT results as compared with posttherapeutic (131)I SPECT/CT may be ascribed to differences in detectability for large lesions (>10 mm) and for no-PSF no-TOF PET, since DEPs are greater than 1%. On the basis of DEPs of 3.5% for lesion diameters of up to 17 mm on no-PSF no-TOF PET, (124)I activities as high as 170 MBq may be warranted to obtain equal detectability.

Value of post-therapeutic ¹³¹I scintigraphy in stimulated serum thyroglobulin-negative patients with metastatic differentiated thyroid carcinoma.

Metastatic differentiated thyroid carcinoma (DTC) with positive (131)I scintigraphy, but negative stimulated Tg (sTg) is relatively rare in clinical practice. The clinical characteristics of these patients were analyzed in the current study. A total of 3367 consecutive histologically proven DTC patients were analyzed retrospectively from January 2007 to June 2013. Tg negativity was defined as a sTg level of <2 ng/mL without positive anti-Tg antibody (TgAb level of <100 IU/mL) under thyroid-stimulating hormone stimulation (TSH level of ≥30 mIU/L). Analyses were performed using the Statistical Package for the Social Sciences, version 20.0 (SPSS, Chicago, IL, USA). Seventy-one patients (median age 45 years, range 17-68 years) were post-therapeutic (131)I-SPECT/CT positive and sTg negative (PTP-TN) constituting 2.1 % of all patients. Of these 71 patients, 2 (2.8 %) had bone metastasis, 11 (15.5 %) had lung metastasis, and 59 (83.1 %) had lymph node metastasis. Fifty-six patients had cervical lymph node metastasis (cLNM), and US was positive in 15 patients (26.8 %), while negative in 41 patients (73.2 %). When compared to patients with concordant positive results for sTg and (131)I scintigraphy, US showed a relatively lower positive rate in the detection of cLNM in PTP-TN patients (28.8 vs. 53.8 %; χ (2) = 6.70; P = 0.01). In conclusion, even with sTg <2 ng/mL, there is a low risk of metastatic DTC. US had limitations in PTP-TN patients, while post-therapy (131)I-SPECT/CT demonstrated an advantage in the detection of functioning metastasis despite low sTg levels in patients with metastatic DTC.

Rare renal metastases from differentiated thyroid carcinoma: early clinical detection and treatment based on radioiodine / Metástases renais raras de carcinoma diferenciado da tireoide: detecção clínica precoce e tratamento com radioiodoterapia

Objective : The aim of this study was to explore the clinical characteristics of renal metastatic cancer, the methods for its detection by radioiodine (131I), and the response to 131I treatment in fourteen patients with renal metastases from differentiated thyroid carcinoma (DTC).Subjects and methods : DTC patients (n = 2,955) that received treatment with 131I were retrospectively analyzed. Scans (131I-WBS, 31I-SPECT/CT and/or 18F-FDG-PET/CT) were performed after an oral therapeutic dose of 131I. Therapeutic efficacy was evaluated based on changes in Tg and anatomical imaging changes at renal lesions.Results : Among these 14 patients, 11 had avidity for 131I, but three patients did not accumulate 131I after 131I treatment. In the 11 131I-positive renal lesions, 10 cases were detected by 131I-SPECT/CT combined with another imaging modality and one case by 131I-WBS combined with ultrasonography (US). In the three 131I-negative renal lesions, two cases were detected by 18F-FDG-PET/CT and one case by computed tomography (CT). In 11 patients with 131I-avid renal metastases, Serum Tg levels in 81.82% (9/11) patients showed a gradual decline, and 18.18% (2/11) of the patients showed a significant elevation. There was no marked difference in serum Tg before the last 131I treatment (Z = 0.157; p = 0.875). Only one patient presented partial response, eight patients exhibited stable disease, and renal metastases progressed in two patients showing progressive disease. No patients reached complete response.Conclusion : 131I-SPECT/CT, combined with another imaging modality after 131I-WBS, can contribute to the early detection of renal metastases of DTC. 131I therapy is a feasible and effective treatment for most DTC renal metastases with avidity for 131I. Arq Bras Endocrinol Metab. 2014;58(3):260-9.

Objetivo : O objetivo deste estudo foi analisar as características clínicas de metástases renais, os métodos para sua detecção por radioiodo (131I) e a resposta ao tratamento com 131I em 14 pacientes com metástases renais de carcinoma diferenciado da tireoide (DTC).Sujeitos e métodos Pacientes com DTC (n = 2.955) que receberam tratamento com 131I foram analisados retrospectivamente. 131I-PCI, 31I-SPECT/CT e/ou 18F-FDG-PET/CT foram feitos após uma dose terapêutica oral de 131I. A eficácia terapêutica foi baseada nas alterações da Tg e nas imagens anatômicas das lesões renais.Resultados : Dos 14 pacientes, 11 apresentaram lesões ávidas por 131I, mas três pacientes não acumularam 131I depois do tratamento com 131I. Nas 11 lesões renais positivas para 131I, 10 casos foram detectados por 131I-SPECT/CT combinado com outra modalidade de exame de imagem e um caso por 131I-WBS combinado com US. Nas três lesões renais negativas para 131I, dois casos foram detectados por 18F-FDG-PET/CT e um caso por tomografia computadorizada (TC). Em 11 pacientes com metástases renais ávidas por 131I, os níveis séricos de Tg em 81,82% (9/11) dos pacientes mostraram um declínio gradual e 18,18% (2/11) apresentaram uma elevação significativa. Não houve diferenças marcadas na Tg sérica antes do último tratamento com 131I (Z = 0,157; p = 0,875). Apenas um paciente apresentou resposta parcial, oito pacientes apresentaram doença estável e as metástases renais progrediram em dois pacientes que apresentaram doença progressiva. Nenhum dos pacientes apresentou resposta completa.Conclusão : 131I-SPECT/CT, combinada com outra modalidade de diagnóstico por imagem após 131I-PCI, pode contribuir para a detecção precoce de metástases renais de DTC. O tratamento ...