The lack of prospective randomized clinical trials for most management topics in differentiated thyroid cancer forces us to make management recommendations based on retrospective observational data, ...which are often incomplete, subject to selection bias, and conflicting. Therefore, it is not surprising that many aspects of thyroid cancer management remain controversial and not well defined. This review will examine the controversies surrounding 3 important topics in thyroid cancer management: the option of thyroid lobectomy as initial therapy, the use of preoperative neck imaging to optimize the completeness of the initial surgery, and the selective use of radioactive iodine for remnant ablation, adjuvant treatment, or treatment for known persistent or recurrent disease. As thyroid cancer management moves toward a much more risk-adapted approach to personalized recommendations, clinicians and patients must balance the risks and benefits of the potential options to arrive at a plan that is optimized regarding both patient preferences/values and the philosophy/experience of the local disease management team.
Inhibition of mitogen-activated protein kinase resulted in an increase in expression of the sodium–iodide symporter in 12 of 20 patients, 8 of whom had sufficient uptake to warrant treatment with ...radioiodine. Five patients had a response, and 3 had stable disease.
Metastatic disease is the most frequent cause of death related to thyroid cancer.
1
Radioiodine (iodine-131) remains a mainstay of therapy for patients with metastatic thyroid cancer of follicular origin (i.e., papillary thyroid cancer or follicular thyroid cancer). Unfortunately, many patients have tumors that do not concentrate iodine, resulting in radioiodine resistance and a poor prognosis (the 10-year survival rate among patients with metastatic thyroid cancer that retains radioiodine avidity is approximately 60%, whereas it is only 10% if the metastases are refractory to radioiodine therapy).
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Several trials have evaluated strategies to “redifferentiate” metastatic thyroid cancers and render them responsive to . . .
The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter ...thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States.
A risk-stratified approach to the evaluation of patients with probable or proven PMC being considered for an active surveillance management approach requires an evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound characteristics (e.g., size of the primary tumor, the location of the tumor within the thyroid gland); (ii) patient characteristics (e.g., age, comorbidities, willingness to accept observation); and (iii) medical team characteristics (e.g., availability and experience of the multidisciplinary team). Based on an analysis of the critical factors within each of these domains, patients with probable or proven PTC can then be classified as ideal, appropriate, or inappropriate candidates for active surveillance.
Risk stratification utilizing the proposed decision-making framework will improve the ability of clinicians to recognize individual patients with proven or probable PMC who are most likely to benefit from an active surveillance management option while at the same time identifying patients with proven or probable PMC that would be better served with an upfront biopsy and surgical management approach.
ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. ...We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long-term survival. Patients with MASC of the thyroid may potentially benefit from Trk molecular-targeted therapy.
Ultrasound and prophylactic dissections have facilitated identification of small-volume cervical lymph node (LN) metastases in patients with papillary thyroid carcinoma (PTC). Since most staging ...systems do not stratify risk based on size or number of LN metastases, even a single-microscopic LN metastasis can upstage a patient with low-risk papillary thyroid microcarcinoma (PMC) to an intermediate risk of recurrence in the American Thyroid Association (ATA) system and to an increased risk of death in the American Joint Committee on Cancer (AJCC) staging system (stage III if the metastatic node is in the central neck or stage IVA if the microscopic LN metastasis is identified in the lateral neck). Such microscopic upstaging may lead to potentially unnecessary or additional treatments and follow-up studies. The goal of this review is to determine if the literature supports the concept that specific characteristics (clinically apparent size, number, and extranodal extension) of LN metastases can be used to stratify the risk of recurrence in PTC.
In patients with pathological proven cervical LN metastases (pathological N1 disease; pN1), the median risk of loco-regional LN recurrence varies markedly by clinical staging, with recurrence rates for patients who are initially clinically N0 (clinical N0 disease; cN0) of 2% (range 0%-9%) versus rates of recurrence for patients who are initially clinically N-positive (clinical N1 disease; cN1) of 22% (range 10%-42%). Furthermore, the median risk of recurrence in pN1 patients varies markedly by the number of positive nodes, <5 nodes (4%, range 3%-8%) vs. >5 nodes (19%, range 7%-21%). Additionally, the presence of extranodal extension was associated with a median risk of recurrence of 24% (range 15%-32%) and possibly a worse disease-specific survival.
Our previous paradigm assigned the same magnitude of risk for all patients with N1 disease. However, small-volume subclinical microscopic N1 disease clearly conveys a much smaller risk of recurrence than large-volume, macroscopic clinically apparent loco-regional metastases. Armed with this information, clinicians will be better able to tailor initial treatment and follow-up recommendations. Implications of N1 stratification for PTC into small-volume microscopic disease versus clinically apparent macroscopic disease importantly relate to issues of prophylactic neck dissection utility, need for pathologic nodal size description, and suggest potential modifications to the AJCC TNM (tumor, nodal disease, and distant metastasis) and ATA risk recurrence staging systems.
Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a ...multidisciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC.
Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop.
The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations.
These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.
Modern management of differentiated thyroid cancer requires individualized care plans that tailor the intensity of therapy and follow-up to the estimated risks of recurrence and disease-specific ...mortality.
This summary is based on the authors' knowledge and extensive clinical experience, supplemented by review of published review articles, thyroid cancer management guidelines, published staging systems, and original articles identified through a PubMed search, which included terms such as risk stratification, staging, clinical outcomes, and differentiated thyroid cancer.
In the past, risk stratification in differentiated thyroid cancer usually referred to a static estimate of disease-specific mortality that was based on a small set of clinicopathological features available within a few weeks of completing initial therapy (thyroidectomy, with or without radioactive iodine). Today, risk stratification is a dynamic, active process used to predict the appropriateness for minimalistic initial therapy, disease-specific mortality, risk of recurrence, and the most likely response to initial therapy. Rather than being a static prediction available only after initial therapy, modern risk stratification is a dynamic, iterative process that begins as soon as a suspicious nodule is detected and continues through final follow-up.
Dynamic risk assessment should be used to guide all aspects of thyroid cancer management, beginning before a definitive diagnosis is made and continuing through the final follow-up visit.
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