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9 pages, 435 KiB

Open AccessArticle

Post-Surgical Ablative or Adjuvant Radioiodine Therapy Has No Impact on Outcome in 1–4 cm Differentiated Thyroid Cancers without Extrathyroidal Extension

by Simone De Leo, Matteo Trevisan, Carla Colombo, Giacomo Gazzano, Sonia Palazzo, Leonardo Vicentini, Luca Persani and Laura Fugazzola

J. Clin. Med. 2021, 10(19), 4452; https://doi.org/10.3390/jcm10194452 - 28 Sep 2021

Cited by 1 | Viewed by 1740

Abstract

Whether to conduct remnant ablation or adjuvant radioactive iodine (RAI) therapy in patients with intrathyroidal differentiated thyroid carcinoma (DTC), sized 1.1–4 cm, is debated. We evaluated the impact of RAI on outcome in this category of DTCs. We retrospectively enrolled 308 patients submitted [...] Read more.

Whether to conduct remnant ablation or adjuvant radioactive iodine (RAI) therapy in patients with intrathyroidal differentiated thyroid carcinoma (DTC), sized 1.1–4 cm, is debated. We evaluated the impact of RAI on outcome in this category of DTCs. We retrospectively enrolled 308 patients submitted to total thyroidectomy: 198 had tumors sized 1.1–2 cm (Group 1) and 110 of 2.1–4 cm (Group 2). Both groups were divided into patients receiving and not receiving RAI after surgery. RAI+ and RAI− patients did not significantly differ, regarding several clinical and pathological features. Final outcome was defined according to dynamic risk stratification. Remission was observed in the majority of Group 1 and Group 2 patients and outcome did not significantly differ between RAI+ and RAI− patients: respectively, 95.8% vs. 93.7% in Group 1, and 87.7% vs. 86.5% in Group 2. The majority of persistent cases, either RAI+ or RAI−, received therapeutic RAI administration, and about 50% of RAI− cases had an excellent response at final follow up, whereas no RAI+ persistent patients had a beneficial effect. Our findings demonstrate that patients with an intrathyroidal DTC sized 1.1–4 cm do not benefit from RAI. The outcome of these patients remains favorable, and the few patients with persistent diseases can be treated with RAI during follow up. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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10 pages, 1199 KiB

Open AccessArticle

Assessing mPTC Progression during Active Surveillance: Volume or Diameter Increase?

by Maria Cristina Campopiano, Antonio Matrone, Teresa Rago, Maria Scutari, Alessandro Prete, Laura Agate, Paolo Piaggi, Rossella Elisei and Eleonora Molinaro

J. Clin. Med. 2021, 10(18), 4068; https://doi.org/10.3390/jcm10184068 - 9 Sep 2021

Cited by 7 | Viewed by 1940

Abstract

Active surveillance (AS) is considered an alternative to immediate surgery in micropapillary thyroid carcinoma (mPTC). However, the definition of clinical mPTC progression during AS is controversial. We evaluated changes in tumor size using both tumor diameters and volume in 109 patients with mPTC [...] Read more.

Active surveillance (AS) is considered an alternative to immediate surgery in micropapillary thyroid carcinoma (mPTC). However, the definition of clinical mPTC progression during AS is controversial. We evaluated changes in tumor size using both tumor diameters and volume in 109 patients with mPTC followed in an AS protocol for a mean period of 31 ± 18 months. At the time of data lock, 19/109 (17.4%) mPTC reached and maintained a volume increase of ≥50%. However, only 3/19 (15.7%) showed progression, according to the diameter increase. The remaining 16 showed a slight diameter growth without reaching the original protocol progression criteria. The mean mPTC growth rate in stable cases was 0.37 mm³/month, while it was significantly greater in the mPTC, which achieved a volume change ≥50% with respect to the other. The two mPTC that developed a significant diameter increase had a growth rate of 41 and 18 mm³/month. Instead, the growth rates of the three mPTC that developed lymph node metastases were 0, 2.5 and 16 mm³/month. The ≥50% volume increase appears to be a too sensitive marker of disease progression, with a downstream higher surgery rate. The assessment of growth rate could distinguish mPTC with high and low growth rates, which would allow us to tailor the algorithm of the evaluations to a more appropriate timing. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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11 pages, 1164 KiB

Open AccessArticle

Combined Mutational and Clonality Analyses Support the Existence of Intra-Tumor Heterogeneity in Papillary Thyroid Cancer

by Marina Muzza, Gabriele Pogliaghi, Luca Persani, Laura Fugazzola and Carla Colombo

J. Clin. Med. 2021, 10(12), 2645; https://doi.org/10.3390/jcm10122645 - 16 Jun 2021

Cited by 5 | Viewed by 1886

Abstract

Despite its potential clinical impact, intra-tumor genetic heterogeneity (ITH) has been scantly investigated in papillary thyroid cancer (PTC). We studied ITH in PTC by combining, for the first time, data derived from the evaluation of the normalized allelic frequencies (NAF) of the mutation/s, [...] Read more.

Despite its potential clinical impact, intra-tumor genetic heterogeneity (ITH) has been scantly investigated in papillary thyroid cancer (PTC). We studied ITH in PTC by combining, for the first time, data derived from the evaluation of the normalized allelic frequencies (NAF) of the mutation/s, using a customized MassARRAY panel, and those obtained by the HUMARA clonality assay. Among tumors with a single mutation, 80% of cases with NAF 50 ± 5% were clonal, consistent with the presence of a single mutated clone, while 20% of cases showed a polyclonal pattern, suggesting the presence of the same mutation in two or more clones. Differently, all cases with NAF < 45% were polyclonal. Among tumors with double mutation, cases with both mutations showing NAF 50 ± 5% were monoclonal, consistent with the presence of a single clone harboring both mutations. On the other hand, all cases with double mutation at NAF < 45% were polyclonal, indicating the presence of two clones with different mutations. Finally, no significant differences in the clinico-pathological characteristics were found between monoclonal and polyclonal tumors. In conclusion, the present study adds insights into the concept of ITH in PTC, which warrants attention because the occurrence of this phenomenon is likely to affect the response to targeted drugs. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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10 pages, 1405 KiB

Open AccessArticle

Improvement of Overall Survival Using TKIs as Salvage Therapy in Advanced Thyroid Carcinoma: Real-Life Data on a Single Center Experience

by Lucia Brilli, Cristina Dalmiglio, Tania Pilli, Filomena Barbato, Fabio Maino, Marco Capezzone, Alessandra Cartocci and Maria Grazia Castagna

J. Clin. Med. 2021, 10(3), 384; https://doi.org/10.3390/jcm10030384 - 20 Jan 2021

Cited by 4 | Viewed by 2284

Abstract

Background: Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients [...] Read more.

Background: Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer. Methods: We retrospectively evaluated 63 patients with progressive advanced thyroid carcinoma treated with TKIs divided into a Study group (23 patients) treated with salvage therapy, and a Control group (40 patients) treated with only one TKI. Results: Similar clinical benefits (stable disease + partial response) and progression free survival between the first and the second line TKI were observed in the Study group (p > 0.99 and p = 0.5, respectively). Median overall survival (OS) was 67.7 months in the Study group and 22.6 months in the Control group (HR 2.46; 95% CI 1.34–4.52, p = 0.004). After stratifying the whole population by age (<65 and ≥65 years), OS was significantly different (p < 0.001) with the best survival curve in younger patients, treated with salvage therapy and the worst in older subjects, treated with only one TKI. Conclusions: Salvage therapy showed a significant improvement of OS in patients with advanced thyroid cancer who experienced disease progression during prior TKI therapies. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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21 pages, 2741 KiB

Open AccessArticle

Clinical Outcome and Toxicity in the Treatment of Anaplastic Thyroid Cancer in Elderly Patients

by Teresa Augustin, Dmytro Oliinyk, Viktoria Florentine Koehler, Josefine Rauch, Claus Belka, Christine Spitzweg and Lukas Käsmann

J. Clin. Med. 2020, 9(10), 3231; https://doi.org/10.3390/jcm9103231 - 9 Oct 2020

Cited by 3 | Viewed by 2186

Abstract

Background: The present study aims to evaluate the outcomes and toxicity of elderly anaplastic thyroid cancer (ATC) patients receiving (chemo)radiotherapy, as well as to identify prognostic factors. Patients and methods: A systematic review using the MEDLINE/PubMed and Cochrane databases was performed. Individual data [...] Read more.

Background: The present study aims to evaluate the outcomes and toxicity of elderly anaplastic thyroid cancer (ATC) patients receiving (chemo)radiotherapy, as well as to identify prognostic factors. Patients and methods: A systematic review using the MEDLINE/PubMed and Cochrane databases was performed. Individual data from all eligible studies were extracted, and a pooled analysis (n = 186) was conducted to examine patient characteristics and treatment. All consecutive ATC patients (≥65 years) treated between 2009 and 2019 at our institution were evaluated for outcomes concerning progression-free survival (PFS), overall survival (OS) probabilities and treatment-related toxicity. Results: The systematic review and pooled analysis identified age as a prognostic factor. The median OS of our patient cohort (n = 26) was three months (range = 0–125). The 6-, 12- and 24-month survival rates were 35%, 22% and 11%, respectively. In the univariate analysis, a Karnofsky performance status of >70%, the Union for International Cancer Control Tumor–Node–Metastasis classification, multimodal therapy and an EQD2 of >49 Gy were correlated with longer OS and PFS. The acute grade 3 toxicity of dysphagia, dyspnea, dermatitis, mucositis and dysphonia was found in 23%, 15%, 12%, 12% and 8% of patients. Conclusion: Age appears to be a prognostic factor in ATC. Elderly ATC patients can tolerate multimodal treatment and achieve a promising outcome. Prospective studies need to confirm our findings. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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13 pages, 626 KiB

Open AccessArticle

Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer

by Evanthia Giannoula, Christos Melidis, Nikitas Papadopoulos, Panagiotis Bamidis, Vasilios Raftopoulos and Ioannis Iakovou

J. Clin. Med. 2020, 9(9), 2708; https://doi.org/10.3390/jcm9092708 - 21 Aug 2020

Cited by 6 | Viewed by 2996

Abstract

Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. [...] Read more.

Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. Identifying these cohorts at an early stage would allow patients at high risk to receive more aggressive treatment while avoiding unnecessary and invasive treatments in those at low risk. Most risk stratification systems include age, tumor size, grade, presence of local invasion, and regional or distant metastases. Here we discuss these common factors as well as their association with treatment response, but also other upcoming markers including histology and multifocality of primary tumor, dose administered and preparation method for Radioiodine Therapy (RAI), Thyroglobulin (Tg), Anti-thyroglobulin Antibodies (Tg-Ab) levels both at initial management and during follow-up, and the presence of previously existing benign thyroid disease. In addition, we examine the role of remnant size and avidity as well as surgeons’ experience in performing thyroidectomies with recurrence rate, discussing its impact on disease prognosis. Our results reveal that treatment response has a statistically significant association with histology, T and M stages, surgeons’ experience, Tg levels and remnant score both during RAI and follow up and Tg-Ab levels during follow-up whole body scan (WBS). Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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Review

Jump to: Research

23 pages, 1961 KiB

Open AccessReview

Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies

by Elisa Stellaria Grassi, Viola Ghiandai and Luca Persani

J. Clin. Med. 2021, 10(7), 1455; https://doi.org/10.3390/jcm10071455 - 1 Apr 2021

Cited by 12 | Viewed by 4209

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are [...] Read more.

Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are hypothesized to drive TC heterogeneity, contributing to its metastatic potential and therapy resistance. CSCs principally exist in tumor areas with specific microenvironmental conditions, the so-called stem cell niches. In particular, in thyroid cancer, CSCs’ survival is enhanced in the hypoxic niche, the immune niche, and some areas with specific extracellular matrix composition. In this review, we summarize the current knowledge about thyroid CSCs, the tumoral niches that allow their survival, and the implications for TC therapy. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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15 pages, 2297 KiB

Open AccessFeature PaperReview

The Impact of the Extent of Surgery on the Long-Term Outcomes of Patients with Low-Risk Differentiated Non-Medullary Thyroid Cancer: A Systematic Meta-Analysis

by Andreea Bojoga, Anna Koot, Johannes Bonenkamp, Johannes de Wilt, Joanna IntHout, Peep Stalmeier, Rosella Hermens, Johannes Smit, Petronella Ottevanger and Romana Netea-Maier

J. Clin. Med. 2020, 9(7), 2316; https://doi.org/10.3390/jcm9072316 - 21 Jul 2020

Cited by 20 | Viewed by 3283

Abstract

Recently, the management of patients with low-risk differentiated non-medullary thyroid cancer (DTC), including papillary and follicular thyroid carcinoma subtypes, has been critically appraised, questioning whether these patients might be overtreated without a clear clinical benefit. The American Thyroid Association (ATA) guideline suggests that [...] Read more.

Recently, the management of patients with low-risk differentiated non-medullary thyroid cancer (DTC), including papillary and follicular thyroid carcinoma subtypes, has been critically appraised, questioning whether these patients might be overtreated without a clear clinical benefit. The American Thyroid Association (ATA) guideline suggests that thyroid lobectomy (TL) could be a safe alternative for total thyroidectomy (TT) in patients with DTC up to 4 cm limited to the thyroid, without metastases. We conducted a meta-analysis to assess the clinical outcomes in patients with low-risk DTC based on the extent of surgery. The risk ratio (RR) of recurrence rate, overall survival (OS), disease-free survival (DFS) and disease specific survival (DSS) were estimated. In total 16 studies with 175,430 patients met the inclusion criteria. Overall, low recurrence rates were observed for both TL and TT groups (7 vs. 7%, RR 1.10, 95% CI 0.61–1.96, I² = 72%), and no statistically significant differences for OS (TL 94.1 vs. TT 94.4%, RR 0.99, CI 0.99–1.00, I² = 53%), DFS (TL 87 vs. TT 91%, RR 0.96, CI 0.89–1.03, I² = 85%), and DSS (TL 97.2 vs. TT 95.4%, RR 1.01, CI 1.00–1.01, I² = 74%). The high degree of heterogeneity of the studies is a notable limitation. Conservative management and appropriate follow-up instead of bilateral surgery would be justifiable in selected patients. These findings highlight the importance of shared-decision making in the management of patients with small, low-risk DTC. Full article

(This article belongs to the Special Issue Recent Advances in Thyroid Cancer)

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