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Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Medical Imaging and Theranostics".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 31079

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Prof. Dr. Angela Spanu

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Nuclear Medicine Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
Interests: nuclear medicine; image-based diagnostics; SPECT; SPECT/CT; PET/CT; molecular breast imaging; oncology (breast cancer, lung cancer, thyroid cancer, neuroendocrine tumors, and prostate cancer); radiomics; neurodegenerative disorders; radiometabolic therapy
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Dr. Giuseppe De Vincentis

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Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy
Interests: nuclear medicine; imaging; integrated imaging; high resolution scintigraphic detectors; heart failure; radionuclide therapy; dosimetry; target alpha therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Coleagues,

Well-differentiated thyroid cancer (DTC), which includes papillary carcinoma and follicular carcinoma, represents the vast majority of all thyroid cancers and the most frequent endocrine malignancy. The incidence of DTC is increasing worldwide due to the widespread use of thyroid ultrasound (US), but mortality is stable over the years as more cancers are diagnosed at a very early stage.

FNAC, in association with neck US, represents the method of choice for the pre-surgical diagnosis and loco-regional staging of DTC.

After surgery, neck US and ¹³¹I-Whole-Body scan, the latter preferably integrated with SPECT/CT, in combination with the serum assay of basal/stimulated Thyroglobulin (TG) and Ab-TG, are currently the diagnostic tools of preference.

¹⁸FDG-PET adds important prognostic information and is especially indicated in the presence of elevated serum levels of TG and a negative radioiodine scan.

Further diagnostic tools, such as computed tomography and MRI, may be considered in selected cases. Moreover, novel diagnostic techniques (e.g., ¹⁸FDG-PET/MRI) and radiotracers (e.g., Tetrafluoroborate) are ongoing in this field.

DTC is usually characterized by a favorable prognosis and maintains the ability to concentrate iodine, thus making the radiometabolic treatment with ¹³¹Iodine (RAI) the most effective therapy after surgery. However, recurrent DTC may become poorly differentiated over time and lose the ability to concentrate iodine. Alternative therapies (e.g., molecular targeted therapy) should be considered in RAI refractory disease.

In this Special Issue, we encourage researchers to submit original papers, review articles, brief communications, or comments on current image-based diagnostics and radiometabolic therapy of DTC. Papers focused on novel diagnostic and therapeutic tools, radiomics, and personalized medicine are also welcome.

Prof. Dr. Angela Spanu
Prof. Dr. Giuseppe De Vincentis
Guest Editors

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Keywords

differentiated thyroid cancer
neck ultrasound
diagnostic radioiodine scan
131I-SPECT/CT
FDG-PET/CT
computed tomography
MRI
PET/MRI
tetrafluoroborate
131I-iodine therapy
dosimetry
theranostics
thyroglobulin
radiomics
personalized medicine

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Published Papers (9 papers)

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11 pages, 801 KiB

Open AccessArticle

2-[¹⁸F]FDG PET in the Management of Radioiodine Refractory Differentiated Thyroid Cancer in the Era of Thyrosin-Kinases Inhibitors: A Real-Life Retrospective Study

by Stefano Gay, Stefano Raffa, Anna De’Luca di Pietralata, Matteo Bauckneht, Lara Vera, Alberto Miceli, Manuela Albertelli, Silvia Morbelli, Massimo Giusti and Diego Ferone

Diagnostics 2022, 12(2), 506; https://doi.org/10.3390/diagnostics12020506 - 16 Feb 2022

Cited by 5 | Viewed by 2302

Abstract

Purpose To evaluate the role of 2-[¹⁸F]FDGPET/CT in the follow-up of radioiodine refractory thyroid cancer (RR-TC). Methods Forty-six 2-[¹⁸F]FDGPET/CT scans from 14 RR-TC patients were considered. Thyroid function tests: thyroglobulin (Tg), levothyroxine (LT4), and tyrosine-kinases inhibitors (TKIs) assumptions were recorded. Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from each scan and correlated with clinical parameters and the overall survival (OS). Results Baseline TLG and MTV predicted OS (p = 0.027 and p = 0.035), and negative correlation with OS was also confirmed when the same parameters were measured in follow-up scans (p = 0.015 and p = 0.021). Tg also correlated with the OS; (p = 0.014; p = 0.019 and p = 0.009). However, TLG and MTV were not significantly correlated with Tg levels. MTV and TLG variation in time were reduced during TKI therapy (p = 0.045 and p = 0.013). Conclusions 2-[¹⁸F]FDGPET/CT confirmed its prognostic role at the first assessment and during the follow-up of RR-TC patients. 2-[¹⁸F]FDGPET/CT parameters seem at least partially independent from Tg. TKI therapy resulted in a measurable effect on the variation of 2-[¹⁸F]FDGPET/CT parameters over time. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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11 pages, 2361 KiB

Open AccessArticle

Shear Wave Elastography and Thyroid Imaging Reporting and Data System (TIRADS) for the Risk Stratification of Thyroid Nodules—Results of a Prospective Study

by Manuela Petersen, Simone A. Schenke, Jonas Firla, Roland S. Croner and Michael C. Kreissl

Diagnostics 2022, 12(1), 109; https://doi.org/10.3390/diagnostics12010109 - 4 Jan 2022

Cited by 17 | Viewed by 2999

Abstract

Purpose: To compare the diagnostic performance of thyroid imaging reporting and data system (TIRADS) in combination with shear wave elastography (SWE) for the assessment of thyroid nodules. Methods: A prospective study was conducted with the following inclusion criteria: preoperative B-mode ultrasound (US) including TIRADS classification (Kwak-TIRADS, EU-TIRADS), quantitative SWE and available histological results. Results: Out of 43 patients, 61 thyroid nodules were detected; 10 nodules were found to be thyroid cancer (7 PTC, 1 FTC, 2 HüCC) and 51 were benign. According to Kwak-TIRADS the majority of benign nodules (47 out of 51, 92.2%) were classified in the low-risk- and intermediate-risk class, four nodules were classified as high-risk (7.8%). When using EU-TIRADS, the benign nodules were distributed almost equally across all risk classes, 21 (41.2%) nodules were classified in the low-risk class, 16 (31.4%) in the intermediate-risk class and 14 (27.4%) in the high-risk class. In contrast, most of the malignant nodules (eight out of ten) were classified as high-risk on EU-TIRADS. One carcinoma was classified as low-risk and one as intermediate-risk nodule. For SWE, ROC analysis showed an optimal cutoff of 18.5 kPa to distinguish malignant and benign nodules (sensitivity 80.0%, specificity 49.0%, PPV 23.5% and NPV 92.6%). The addition of elastography resulted in an increase of accuracy from 65.6% to 82.0% when using Kwak-TIRADS and from 49.2% to 72.1% when using EU-TIRADS. Conclusion: Our data demonstrate that the combination of TIRADS and SWE seems to be superior for the risk stratification of thyroid nodules than each method by itself. However, verification of these results in a larger patient population is mandatory. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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10 pages, 7188 KiB

Open AccessArticle

Deep Learning Based Fast Screening Approach on Ultrasound Images for Thyroid Nodules Diagnosis

by Hafiz Abbad Ur Rehman, Chyi-Yeu Lin and Shun-Feng Su

Diagnostics 2021, 11(12), 2209; https://doi.org/10.3390/diagnostics11122209 - 26 Nov 2021

Cited by 8 | Viewed by 3210

Abstract

Thyroid nodules are widespread in the United States and the rest of the world, with a prevalence ranging from 19 to 68%. The problem with nodules is whether they are malignant or benign. Ultrasonography is currently recommended as the initial modality for evaluating thyroid nodules. However, obtaining a good diagnosis from ultrasound imaging depends entirely on the radiologists levels of experience and other circumstances. There is a tremendous demand for automated and more reliable methods to screen ultrasound images more efficiently. This research proposes an efficient and quick detection deep learning approach for thyroid nodules. An open and publicly available dataset, Thyroid Digital Image Database (TDID), is used to determine the robustness of the suggested method. Each image is formatted into a pyramid tile-based data structure, which the proposed VGG-16 model evaluates to provide segmentation results for nodular detection. The proposed method adopts a top-down approach to hierarchically integrate high- and low-level features to distinguish nodules of varied sizes by employing fuse features effectively. The results demonstrated that the proposed method outperformed the U-Net model, achieving an accuracy of 99%, and was two times faster than the competitive model. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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9 pages, 1537 KiB

Open AccessArticle

Whole-Body Radioiodine Effective Half-Life in Patients with Differentiated Thyroid Cancer

by Michele Klain, Carmela Nappi, Marina De Risi, Leandra Piscopo, Fabio Volpe, Mariarosaria Manganelli, Elisa Caiazzo, Davide Bianco, Martin Schlumberger and Alberto Cuocolo

Diagnostics 2021, 11(10), 1740; https://doi.org/10.3390/diagnostics11101740 - 22 Sep 2021

Cited by 8 | Viewed by 3446

Abstract

Background: Radioactive ¹³¹I (RAI) therapy is used in patients with differentiated thyroid cancer (DTC) after total thyroidectomy for remnant ablation, adjuvant treatment or treatment of persistent disease. ¹³¹I retention data, which are used to indicate the time at which a ¹³¹I treated DTC patient can be released from the hospital, may bring some insights regarding clinical factors that prolong the length of hospitalization. The aim of this study was to investigate the ¹³¹I whole-body retention in DTC patients during ¹³¹I therapy. Methods: We monitored 166 DTC patients to follow the ¹³¹I whole-body retention during ¹³¹I therapy with a radioactivity detector fixed on the ceiling of each protected room. A linear regression fit permitted us to estimate the whole-body ¹³¹I effective half-life in each patient, and a relationship was sought between patients’ clinical characteristics and whole-body effective ¹³¹I half-life. Results: The effective ¹³¹I half-life ranged from 4.08 to 56.4 h. At multivariable analysis, longer effective ¹³¹I half-life was related to older age and extensive extra-thyroid disease. Conclusions: ¹³¹I effective half-life during ¹³¹I treatment in DTC patients is highly variable among patients and is significantly longer in older and in patients with RAI uptake in large thyroid remnants or in extrathyroidal disease that significantly prolongs the whole-body retention of ¹³¹I. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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20 pages, 2885 KiB

Open AccessArticle

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

by Angela Spanu, Susanna Nuvoli, Andrea Marongiu, Ilaria Gelo, Luciana Mele, Andrea De Vito, Maria Rondini and Giuseppe Madeddu

Diagnostics 2021, 11(8), 1504; https://doi.org/10.3390/diagnostics11081504 - 20 Aug 2021

Cited by 13 | Viewed by 3992

Abstract

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. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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12 pages, 695 KiB

Open AccessArticle

Impact of 18F-FDG PET/CT on Clinical Management of Suspected Radio-Iodine Refractory Differentiated Thyroid Cancer (RAI-R-DTC)

by Elisa Lodi Rizzini, Andrea Repaci, Elena Tabacchi, Lucia Zanoni, Valentina Vicennati, Ottavio Cavicchi, Uberto Pagotto, Alessio Giuseppe Morganti, Stefano Fanti and Fabio Monari

Diagnostics 2021, 11(8), 1430; https://doi.org/10.3390/diagnostics11081430 - 7 Aug 2021

Cited by 8 | Viewed by 2837

Abstract

Background: As reported in the literature, [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) provides useful qualitative and semi-quantitative data for the prognosis of advanced differentiated thyroid cancer. Instead, there is a lack of data about the real clinical impact of 18F-FDG PET/CT on the choice of the more effective therapeutic approach for advanced differentiated thyroid cancer (DTC) that starts to lose iodine avidity. The primary aim of this retrospective study was to assess how 18F-FDG PET/CT can guide the choice of the best therapeutic approach to RAI-refractory DTC (RAI-R-DTC) in patients with a doubtful iodine uptake/negative 18F-FDG PET/CT I whole-body scan after several radioactive iodine therapies (RAIT). The secondary aim was to assess the prognostic role of clinical and semi-quantitative metabolic 18F-FDG PET/CT parameters in comparison to published data. Materials and methods: A monocentric retrospective observational study was performed, reviewing the medical records of 53 patients recruited from a database of 208 patients treated at our Institution between 2011 and 2019, with advanced DTC that underwent FDG PET/CT scan for a suspected RAI-R-DTC. Selected patients had to perform a 18F-FDG PET/CT scan after the second RAIT based on a doubtful iodine uptake/negative 131 I whole-body scan and/or persistent elevated thyroglobulin levels. Metabolic response was defined according to positron emission tomography response criteria in solid tumors (PERCIST) guidelines. Standardized uptake value (SUV)max, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The association between metabolic features, clinical parameters and progression free survival (PFS) was assessed applying Kruskal–Wallis, chi-square-Pearson correlation tests, and Cox regression analyses when appropriate. Results: Among our sample of 53 patients (mean age 52.0 ± 19.9 years; 31 women and 22 men), 27 (51.0%) presented a positive 18F-FDG PET/CT scan: 16 (59.0%) underwent watchful waiting, 4 (15.0%) received external-beam radiation therapy (EBRT), 4 (15.0%) underwent surgery, 2 (7.4%) received another course of RAI therapy, and 1 underwent surgery + EBRT. PERCIST response was evaluated in 14/27 patients. Median follow-up was 5.8 ± 3.9 years and median PFS was 38.0 ± 21.8 months. At the last follow-up assessment, 14/53 (26.4%) demonstrated disease progression, 13/53 (24.5) persistence of structural disease, 25/53 (47%) persistence of biochemical disease, and 15/53 (28%) had an excellent response. A significant association was found between therapeutic approach, metabolic response, and final disease response evaluation, as well as a linear correlation between MTV and TLG with thyroglobulin level. Conclusions: Our Institutional experience confirmed the role of 18F-FDG PET/CT as a useful guide in the clinical management of RAI-R-DTC and obviated further unnecessary RAIT. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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13 pages, 1819 KiB

Open AccessArticle

A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [¹⁸F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer

by Hong Hua Piao, Subin Jeon, Su Woong Yoo, Young Jae Ryu, Dong-Yeon Kim, Ayoung Pyo, Hee-Seung Bom, Jung-Joon Min and Seong Young Kwon

Diagnostics 2021, 11(5), 836; https://doi.org/10.3390/diagnostics11050836 - 6 May 2021

Cited by 1 | Viewed by 2392

Abstract

We investigated whether an indication for [¹⁸F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [¹⁸F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy. The MLN ratio (LNR) was defined as the ratio of the number of MLNs to the number of removed LNs. To derive the LNR-combined criteria, different Tg cut-off values for identifying the PET/CT-indicated group for PD detection were applied individually to subgroups initially classified based on LNR cut-off values. The cut-off values for serum Tg, the number of MLNs, and LNR for a PET/CT indication were 6.0 ng/mL, 5, and 0.51, respectively. Compared to a single parameter (serum Tg, total number of MLNs, and LNR), the LNR-combined criteria showed significantly superior diagnostic performance in detecting FDG-avid PD (p < 0.001). The diagnostic performance of PET/CT in detecting FDG-avid PD was significantly improved when the PET/CT-indicated group was identified through the LNR-combined criteria in a stepwise manner; this can contribute to a customized PET/CT indication in PTC patients. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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Review

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12 pages, 733 KiB

Open AccessReview

Early Predictive Response to Multi-Tyrosine Kinase Inhibitors in Advanced Refractory Radioactive-Iodine Differentiated Thyroid Cancer: A New Challenge for [¹⁸F]FDG PET/CT

by Cristina Ferrari, Giulia Santo, Rossella Ruta, Valentina Lavelli, Dino Rubini, Paolo Mammucci, Angela Sardaro and Giuseppe Rubini

Diagnostics 2021, 11(8), 1417; https://doi.org/10.3390/diagnostics11081417 - 5 Aug 2021

Cited by 5 | Viewed by 2822

Abstract

Differentiated thyroid cancer (DTC) represents the most common thyroid cancer histotype. Generally, it exhibits a good prognosis after conventional treatments; nevertheless, about 20% of patients can develop a local recurrence and/or distant metastasis. In one-third of advanced DTC, the metastatic lesions lose the ability to take up iodine and become radioactive iodine-refractory (RAI-R) DTC. In this set of patients, the possibility to perform localized treatments should always be taken into consideration before the initiation of systemic therapy. In the last decade, some multi-tyrosine kinase inhibitor (MKI) drugs were approved for advanced DTC, impacting on patient’s survival rate, but at the same time, these therapies have been associated with several adverse events. In this clinical context, the role of 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) in the early treatment response to these innovative therapies was investigated, in order to assess the potentiality of this diagnostic tool in the early recognition of non-responders, avoiding unnecessary therapy. Herein, we aimed to present a critical overview about the reliability of [¹⁸F]FDG PET/CT in the early predictive response to MKIs in advanced differentiated thyroid cancer. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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20 pages, 9640 KiB

Open AccessReview

Thyroid Nodule Characterization: How to Assess the Malignancy Risk. Update of the Literature

by Daniele Fresilli, Emanuele David, Patrizia Pacini, Giovanni Del Gaudio, Vincenzo Dolcetti, Giuseppe Tiziano Lucarelli, Nicola Di Leo, Maria Irene Bellini, Vito D'Andrea, Salvatore Sorrenti, Domenico Mascagni, Marco Biffoni, Cosimo Durante, Giorgio Grani, Giuseppe De Vincentis and Vito Cantisani

Diagnostics 2021, 11(8), 1374; https://doi.org/10.3390/diagnostics11081374 - 30 Jul 2021

Cited by 42 | Viewed by 5420

Abstract

Ultrasound (US) is the first imaging modality for thyroid parenchyma evaluation. In the last decades, the role of ultrasound has been improved with the introduction of new US software, such as contrast-enhanced ultrasound (CEUS) and US-elastography (USE). USE is nowadays recognized as an essential part of the multiparametric ultrasound (MPUS) examination, in particular for the indeterminate thyroid nodule with possible fine-needle aspiration cytology (FNAC) number reduction; even if further and larger studies are needed to validate it. More controversial is the role of CEUS in thyroid evaluation, due to its high variability in sensitivity and specificity. Semi-automatic US systems based on the computer-aided diagnosis (CAD) system are producing interesting results, especially as an aid to less experienced operators. New knowledge on the molecular mechanisms involved in thyroid cancer is allowing practitioners to identify new genomic thyroid markers that could reduce the number of “diagnostic” thyroidectomies. We have therefore drawn up an updated representation of the current evidence in the literature for thyroid nodule multiparametric ultrasound (MPUS) evaluation with particular regard to USE, the US CAD system and CEUS. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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