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2020 Update on the Management of Thyroid Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 43486

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Special Issue Editor

Prof. Iwao Sugitani

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Guest Editor

Department of Endocrine Surgery, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603 Japan
Interests: thyroid cancer surgery; active surveillance for low-risk papillary thyroid carcinoma; targeted therapy for advanced differentiated or anaplastic thyroid carcinoma

Special Issue Information

Dear colleagues,

During the past several years, the management of thyroid cancers has moved toward individualized care based on adequate risk stratification systems. A rapid increase in the incidence of small, nonlethal papillary thyroid carcinoma has been reported from many developed countries, raising a modern issue of overdiagnosis and overtreatment of those carcinomas. The 2015 American Thyroid Association guidelines recommended lobectomy for intrathyroidal papillary thyroid carcinomas 1–4 cm in diameter and active surveillance for very low-risk papillary thyroid carcinomas. In addition, the recent advent of molecular diagnostic tools is also expected to reduce unnecessary surgeries for patients with indeterminate thyroid nodules. Moreover, terms like “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” were introduced as borderline tumors in an attempt to avoid overdiagnosis and overtreatment for an indolent subset of neoplasms previously termed malignant. On the other hand, the treatment outcomes of nonradioactive iodine avid, progressive differentiated thyroid carcinoma and anaplastic thyroid carcinoma are still challenging. However, new therapeutic agents including not only conventional multikinase inhibitors but also agents with more specific targets have been developed and tested, based on the examination of each tumor’s gene expression pattern. In this trend of personalized medicine, the importance of patient-reported outcome studies has been increasing.

In this Special Issue, experts will review the current management of patients with the wide spectrum of thyroid cancer.

Prof. Iwao Sugitani
Guest Editor

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Keywords

risk stratification in differentiated thyroid carcinoma
conservative surgery for low-risk papillary thyroid carcinoma
active surveillance for very low-risk papillary thyroid carcinoma
molecular testing for indeterminate thyroid nodules
borderline thyroid tumors like NIFTP
therapeutic options of systemic therapy for advanced thyroid cancer
patient-reported outcomes in the management of thyroid cancer

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Published Papers (10 papers)

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Research

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11 pages, 22060 KiB

Open AccessArticle

Optimal Management of the Unilateral Recurrent Laryngeal Nerve Involvement in Patients with Thyroid Cancer

by Satoru Miyamaru, Daizo Murakami, Kohei Nishimoto, Narihiro Kodama, Joji Tashiro, Yusuke Miyamoto, Haruki Saito, Hiroki Takeda, Momoko Ise and Yorihisa Orita

Cancers 2021, 13(9), 2129; https://doi.org/10.3390/cancers13092129 - 28 Apr 2021

Cited by 7 | Viewed by 2652

Abstract

We aimed to determine the optimal management of recurrent laryngeal nerve (RLN) involvement in thyroid cancer. We enrolled 80 patients with unilateral RLN involvement in thyroid cancer between 2000 and 2016. Eleven patients with preoperatively functional vocal folds (VFs) underwent sharp tumor resection to preserve the RLN (shaving group). Thirty-three patients underwent RLN reconstruction with RLN resection (reconstruction group). We divided the reconstruction group into two subgroups based on preoperative VF mobility (normal-reconstruction and paralyzed-reconstruction subgroups). In the cases where RLN reconstruction was difficult, phonosurgeries including arytenoid adduction (AA), with or without thyroplasty type I, or nerve muscle pedicle implantation with AA were performed later (phonosurgery group). We evaluated and compared vocal function among the evaluated periods and different groups. Postoperative vocal function in the shaving and normal-reconstruction subgroups was favorable. There were no significant differences between the two groups. In the paralyzed-reconstruction and phonosurgery groups, postoperative vocal function was significantly improved, and vocal function in the paralyzed-reconstruction subgroup was significantly better than that in the phonosurgery group. For optimal management of unilateral RLN involvement in thyroid cancer, first, sharp dissection should be performed, and if this is impossible, a simultaneous RLN reconstruction procedure should be adopted whenever possible. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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12 pages, 569 KiB

Open AccessArticle

Additional Tissue Sampling Trials Did Not Change Our Thyroid Practice

by Hisakazu Shindo, Kennichi Kakudo, Keiko Inomata, Yusuke Mori, Hiroshi Takahashi, Shinya Satoh and Hiroyuki Yamashita

Cancers 2021, 13(6), 1270; https://doi.org/10.3390/cancers13061270 - 12 Mar 2021

Cited by 3 | Viewed by 1991

Abstract

This study aimed to determine whether additional tissue sampling of encapsulated thyroid nodules would increase the frequency of follicular thyroid carcinoma (FTC) diagnoses. We examined thyroid tissue specimens from 86 patients suspected of FTC (84.9% female; mean age, 49.0 ± 17.8 years). The number of tissue blocks created for pathological assessments ranged from 3 to 20 (mean, 9.1 ± 4.1); the numbers in the previous method recommended by the Japanese General Rules for the Description of Thyroid Cancer and additional blocks ranged from 1 to 12 (mean, 6.0 ± 2.8) and from 1 to 8 (mean, 3.1 ± 2.0), respectively. The additional blocks were subsequently examined to determine whether any diagnoses changed from those based on the previous method. Five patients were diagnosed with FTC using the previous method; however, additional tissue blocks led to the diagnosis of FTC in 6 patients, as 1 diagnosis was revised from follicular adenoma to FTC. It has been reported that increasing the number of tissue blocks used for pathological assessments can increase the frequency of FTC diagnoses; however, this was not clinically significant in thyroid carcinoma, which requires completion thyroidectomy and radioactive iodine treatment. It resulted in no benefits to the patient because all minimally invasive FTCs, follicular tumors of uncertain malignant potential (FT-UMP), and follicular adenomas are treated with lobectomy alone in Japan. Additional tissue sampling only had a slight impact on our thyroid practice; therefore, we decided to cease it. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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15 pages, 5215 KiB

Open AccessArticle

Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models

by Keisuke Enomoto, Shun Hirayama, Naoko Kumashiro, Xuefeng Jing, Takahito Kimura, Shunji Tamagawa, Ibu Matsuzaki, Shin-Ichi Murata and Muneki Hotomi

Cancers 2021, 13(4), 862; https://doi.org/10.3390/cancers13040862 - 18 Feb 2021

Cited by 6 | Viewed by 3086

Abstract

E7080, known as lenvatinib, is an oral multitargeted tyrosine kinase inhibitor that has been shown to improve the survival rate of patients with radioiodine-refractory thyroid cancer. However, a majority of patients do not continue lenvatinib intake due to disease progression or significant toxicity. To improve treatment success rates, we propose the combination of lenvatinib with mitogen-activated protein kinase (MEK) inhibitors. To test this hypothesis, we tested the effects of lenvatinib with the MEK inhibitor U0126 in vitro using two human anaplastic thyroid cancer (ATC) cell lines, 8505C and TCO1, and with another MEK inhibitor, selumetinib (AZD6244), in an ATC mouse model. We found that the combination of lenvatinib with MEK inhibitors enhanced the antitumor effects of monotherapy with either agent in vitro and in vivo, and these effects may be through the AKT (Protein Kinase B) and extracellular signal-regulated kinase (ERK) signaling pathways. Furthermore, the combination does not have significant adverse effects in the ATC mouse models in terms of body weight, blood biochemical parameters, and histopathology. In conclusion, the combination of lenvatinib with an MEK inhibitor is a potentially viable therapeutic approach for ATC treatment. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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11 pages, 739 KiB

Open AccessArticle

Decision-making in Surgery or Active Surveillance for Low Risk Papillary Thyroid Cancer During the COVID-19 Pandemic

by Anna M. Sawka, Sangeet Ghai, Ogemdi Ihekire, Jennifer M. Jones, Amiram Gafni, Nancy N. Baxter, David P. Goldstein and on behalf of the Canadian Thyroid Cancer Active Surveillance Study Group

Cancers 2021, 13(3), 371; https://doi.org/10.3390/cancers13030371 - 20 Jan 2021

Cited by 10 | Viewed by 3803

Abstract

We describe our experience conducting a prospective observational cohort study on the management of small, low risk papillary thyroid cancer during the COVID-19 pandemic. Our study participants are given the choice of active surveillance (AS) or surgery, and those in the AS arm are followed at the study center, whereas surgical patients undergo usual care. During the pandemic we have transitioned from in-person research patient visits to largely virtual care of patients under AS. As of 30 October 2020, we had enrolled 181 patients enrolled in our study (including 25 during the pandemic), of which 92.3% (167/181) consented to telephone communication and 79.0% (143/181) consented to secure videoconferencing communication. Prior to the pandemic, 74.5% (117/157) of our patients chose AS over surgery, whereas during the pandemic, 96.0% (24/25) chose AS. Of the 133 study patients who were under AS within the timeframe from 12 March 2020, to 30 October 2020, the percentage of patients who missed appointments was 8.3% (11/133, for neck ultrasound and physician visits, respectively) and delayed appointments was 23.3% (31/133). This preliminary data suggests that prospective observational research on AS of thyroid cancer can safely continue during the pandemic. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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14 pages, 1647 KiB

Open AccessArticle

TERT Promoter Mutation and Extent of Thyroidectomy in Patients with 1–4 cm Intrathyroidal Papillary Carcinoma

by Aya Ebina, Yuki Togashi, Satoko Baba, Yukiko Sato, Seiji Sakata, Masashi Ishikawa, Hiroki Mitani, Kengo Takeuchi and Iwao Sugitani

Cancers 2020, 12(8), 2115; https://doi.org/10.3390/cancers12082115 - 30 Jul 2020

Cited by 15 | Viewed by 2792

Abstract

There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1–4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, p < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, p < 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1–4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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Review

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18 pages, 998 KiB

Open AccessReview

Management of VEGFR-Targeted TKI for Thyroid Cancer

by Tomohiro Enokida and Makoto Tahara

Cancers 2021, 13(21), 5536; https://doi.org/10.3390/cancers13215536 - 4 Nov 2021

Cited by 20 | Viewed by 3755

Abstract

Recent advances in the development of multitarget tyrosine kinase inhibitors (MTKIs), which mainly target the vascular endothelial growth factor receptor (VEGFR), have improved prognoses and dramatically changed the treatment strategy for advanced thyroid cancer. However, adverse events related to this inhibition can interrupt treatment and sometimes lead to discontinuation. In addition, they can be annoying and potentially jeopardize the subjects’ quality of life, even allowing that the clinical outcome of patients with advanced thyroid cancer remains limited. In this review, we summarize the potential mechanisms underlying these adverse events (hypertension, proteinuria and renal impairment, hemorrhage, fistula formation/gastrointestinal perforation, wound healing, cardiovascular toxicities, hematological toxicity, diarrhea, fatigue, and acute cholecystitis), their characteristics, and actual management. Furthermore, we also discuss the importance of related factors, including alternative treatments that target other pathways, the necessity of subject selection for safer administration, and patient education. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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11 pages, 1719 KiB

Open AccessReview

Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan

by Hiroki Shimura, Yoshiko Matsumoto, Tsukasa Murakami, Nobuhiro Fukunari, Masafumi Kitaoka and Shinichi Suzuki

Cancers 2021, 13(18), 4629; https://doi.org/10.3390/cancers13184629 - 15 Sep 2021

Cited by 15 | Viewed by 8499

Abstract

In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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13 pages, 480 KiB

Open AccessReview

Surgical Management of Tracheal Invasion by Well-Differentiated Thyroid Cancer

by Fumihiko Matsumoto and Katsuhisa Ikeda

Cancers 2021, 13(4), 797; https://doi.org/10.3390/cancers13040797 - 14 Feb 2021

Cited by 16 | Viewed by 3573

Abstract

Well-differentiated thyroid carcinoma (WDTC) is a slow-growing cancer with a good prognosis, but may show extraglandular progression involving the invasion of tumor-adjacent tissues, such as the trachea, esophagus, and recurrent laryngeal nerve. Tracheal invasion by WDTC is infrequent. Since this condition is rare, relevant high-level evidence about it is lacking. Tracheal invasion by a WDTC has a negative impact on survival, with intraluminal tumor development constituting a worse prognostic factor than superficial tracheal invasion. In WDTC, curative resection is often feasible with a small safety margin, and complete resection can ensure a good prognosis. Despite its resectability, accurate knowledge of the tracheal and peritracheal anatomy and proper selection of surgical techniques are essential for complete resection. However, there is no standard guideline on surgical indications and the recommended procedure in trachea-invading WDTC. This review discusses the indications for radical resection and the three currently available major resection methods: shaving, window resection, and sleeve resection with end-to-end anastomosis. The review shows that the decision for radical resection should be based on the patient’s general condition, tumor status, expected survival duration, and the treating facility’s strengths and weaknesses. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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14 pages, 1971 KiB

Open AccessReview

Thyroid Hürthle Cell Carcinoma: Clinical, Pathological, and Molecular Features

by Shoko Kure and Ryuji Ohashi

Cancers 2021, 13(1), 26; https://doi.org/10.3390/cancers13010026 - 23 Dec 2020

Cited by 27 | Viewed by 8043

Abstract

Hürthle cell carcinoma (HCC) represents 3–4% of thyroid carcinoma cases. It is considered to be more aggressive than non-oncocytic thyroid carcinomas. However, due to its rarity, the pathological characteristics and biological behavior of HCC remain to be elucidated. The Hürthle cell is characterized cytologically as a large cell with abundant eosinophilic, granular cytoplasm, and a large hyperchromatic nucleus with a prominent nucleolus. Cytoplasmic granularity is due to the presence of numerous mitochondria. These mitochondria display packed stacking cristae and are arranged in the center. HCC is more often observed in females in their 50–60s. Preoperative diagnosis is challenging, but indicators of malignancy are male, older age, tumor size > 4 cm, a solid nodule with an irregular border, or the presence of psammoma calcifications according to ultrasound. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas, or clinically detectable cervical nodal metastases, but total thyroidectomy is recommended for tumors larger than 4 cm. The effectiveness of radioactive iodine is still debated. Molecular changes involve cellular signaling pathways and mitochondria-related DNA. Current knowledge of Hürthle cell carcinoma, including clinical, pathological, and molecular features, with the aim of improving clinical management, is reviewed. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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18 pages, 275 KiB

Open AccessReview

Thyroid Lobectomy for Low to Intermediate Risk Differentiated Thyroid Cancer

by Dana M. Hartl, Joanne Guerlain, Ingrid Breuskin, Julien Hadoux, Eric Baudin, Abir Al Ghuzlan, Marie Terroir-Cassou-Mounat, Livia Lamartina and Sophie Leboulleux

Cancers 2020, 12(11), 3282; https://doi.org/10.3390/cancers12113282 - 6 Nov 2020

Cited by 23 | Viewed by 3874

Abstract

Many recent publications and guidelines have promoted a “more is less” approach in terms of treatment for low to intermediate risk differentiated thyroid cancer (DTC), which comprise the vast majority of thyroid cancers: less extensive surgery, less radioactive iodine, less or no thyroid hormone suppression, and less frequent or stringent follow-up. Following this approach, thyroid lobectomy has been proposed as a means of decreasing short- and long-term postoperative morbidity while maintaining an excellent prognosis for tumors meeting specific macroscopic and microscopic criteria. This article will examine the pros and cons of thyroid lobectomy for low to intermediate risk cancers and discuss, in detail, criteria for patient selection and oncological outcomes. Full article

(This article belongs to the Special Issue 2020 Update on the Management of Thyroid Cancer)

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