Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Predictive factors of outcome in poorly differentiated thyroid carcinomas.

BACKGROUND: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis. METHODS: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome). RESULTS: All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10-0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions -124 (C228T) and -146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations. CONCLUSION: PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness.

Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age.

BACKGROUND: This study validated the dynamic risk stratification (DRS) system with regard to its association with structural recurrence and risk factors associated with non-excellent responses in patients <45 years with stage I classical papillary thyroid cancer (PTC). METHODS: This historical cohort study included 598 patients with stage I classical PTC <45 years of age treated with total thyroidectomy followed by radioactive iodine remnant ablation (n = 440), total thyroidectomy without radioactive iodine remnant ablation (n = 23), and thyroid lobectomy alone (n = 135). RESULTS: The median follow-up period was 123 months. Structural recurrence occurred in 4.2% (n = 18/432) of the patients with an excellent response, 17.1% (18/105) of patients with an indeterminate response, 44.7% (17/38) of patients with a biochemically incomplete response, and 82.6% (19/23) of patients with a structurally incomplete response (p < 0.001) during the follow-up. The disease-free survival curves of each response showed significant differences (p < 0.001). Extensive extrathyroidal extension and extranodal extension were the independent risk factors associated with non-excellent response (p < 0.05). CONCLUSIONS: DRS may reduce unnecessary additional treatments by reclassifying initial risk estimates of structural recurrence. Furthermore, applying the risk factors associated with non-excellent response to initial therapy may be a more useful and viable surrogate of the risk for structural recurrence in stage I PTC patients <45 years of age.

Facilitating anaplastic thyroid cancer specialized treatment: A model for improving access to multidisciplinary care for patients with anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Several treatment trials are available, but the number of eligible patients to participate is very low because of the rarity and aggressiveness of the disease. METHODS: Facilitating Anaplastic Thyroid Cancer Specialized Treatment (FAST) is a quality improvement project aimed at decreasing time from referral to disposition (scheduling of first appointment) to our institution. After identifying reasons for delays, we created a new process flow specifically for patients with ATC allowing patients to be scheduled immediately. RESULTS: Historical data revealed a mean referral to disposition time for patients with ATC of 8.7 days before our intervention. After the intervention, the mean referral to disposition time was reduced to 0.5 days. Participation in treatment trials for all patients with ATC was 34%. CONCLUSION: Since the implementation of FAST, the access time has decreased and the number of successful referrals for ATC has increased significantly.

Postoperative radioactive iodine-131 ablation is not necessary among patients with intermediate-risk differentiated thyroid carcinoma: a population-based study.

OBJECTIVE: To assess the effectiveness of radioactive iodine (RAI) ablation among patients with intermediate-risk differentiated thyroid cancer (DTC) following surgery. SUBJECTS AND METHODS: This population based study obtained information from the Surveillance, Epidemiology, and End Results (SEER) Program Research Data (1973-2013). National Cancer Institute, DCCPS, Surveillance Research Programme, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. A total of 93,530 patients with primary thyroid cancer were identified in the SEER database during the period of 2004-2013 and focused on patients with DTC post-operatively treated or not treated with radioactive iodine (RAI). From these 9,127 patients were selected who had intermediate-risk DTC. A total of 8,601 patients were included in this study. For the overall population, the mean age of the population was 47.3 years and the majority were female (70.5%). RESULTS: Kaplan-Meier analysis found the mean overall survival time (os) for subjects with no radiation therapy which was 112.9 months and 114.9 months for those who received RAI ablation treatment (P<0.001). However, thyroid cancer-specific survival was not significantly different between treatment groups (117.7 vs. 118.0 months, log-rank test P=0.164). Overall survival and thyroid cancer-specific 1 year, 5 years, and 10-years survival rates were ≥89.8% and were similar between both treated groups. Multivariate analysis found age, gender, histologic type, and degree of lymph node metastases to be associated with OS, and age, gender, degree of lymph node metastasis and extra-thyroid tumor spread were independent factors for cancer-specific survival. In DTC patients with intermediate cancer risk multivariate analysis found that RAI was associated with a reduced risk of mortality compared with no radiation therapy (HR=0.710, 95% CI: 0.562-0.897, P=0.004) but no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category. CONCLUSION: In DTC patients with intermediate cancer risk although postoperative RAI ablation following surgery showed a benefit in overall survival, no significant difference was seen in cancer-specific survival, either based on whole study population or on tumor size category.

Application of the new American Thyroid Association guidelines leads to a substantial rate of completion total thyroidectomy to enable adjuvant radioactive iodine.

BACKGROUND: The recently published 2015 American Thyroid Association guidelines recognize lobectomy as a viable alternative for low-risk cancers and advise more conservative use of radioactive iodine. Some factors indicating adjuvant treatment with radioactive iodine (and therefore completion total thyroidectomy), however, only can be found upon pathologic investigation. METHODS: We performed a retrospective analysis including patients with American Thyroid Association low- and low-to-intermediate risk well-differentiated thyroid cancer 1-4 cm. We evaluated how often radioactive iodine would be indicated and compared this with our historic rate. A subanalysis was performed to determine the rate of completion total thyroidectomy necessary, based on the indications for adjuvant radioactive iodine therapy. RESULTS: A total of 394/1,000 (39.4%) patients were included for final analysis. Adjuvant radioactive iodine would have been favored in 101/394 (25.6%) of patients, which is 2.5 times less than was given in our historic cohort. Completion total thyroidectomy to enable adjuvant radioactive iodine would have been recommended in 29/149 (19.5%) patients preoperatively eligible for lobectomy. CONCLUSION: Despite the tightened regulations for radioactive iodine, about 20% of patients with apparently "low-risk" well-differentiated thyroid cancer who are eligible for lobectomy may need completion total thyroidectomy because of pathologic findings for which radioactive iodine use is listed as considered or favored by the current guidelines.

Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci. RESULTS: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013). CONCLUSIONS: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

In differentiated thyroid cancer, an incomplete structural response to therapy is associated with significantly worse clinical outcomes than only an incomplete thyroglobulin response.

BACKGROUND: We previously demonstrated the clinical utility of using response to therapy variables obtained during the first 2 years of follow-up to actively modify initial risk estimates which were obtained using standard clinic-pathologic staging systems. While our proposed dynamic risk stratification system accurately reclassified patients who demonstrated an excellent response to therapy as low-risk patients, it grouped patients with either biochemical or structural evidence of disease into a single incomplete response to therapy cohort. This cohort included a wide variety of patients ranging from very minor thyroglobulin (Tg) elevations in the absence of structurally identifiable disease to widespread, progressive structural disease. Here we determined whether subdivision of the incomplete response to therapy category more precisely predicted clinical outcomes. We hypothesized that patients with an incomplete response to therapy based on persistently abnormal Tg values alone would have better clinical outcomes than patients having structurally identifiable disease. METHODS: Following total thyroidectomy and radioactive iodine (RAI) ablation, 192 adult thyroid cancer patients were retrospectively identified as having either a biochemical incomplete response (abnormal Tg without structural evidence of disease) or structural incomplete response (structurally identifiable disease with or without abnormal Tg) as the best response to initial therapy within the first 24 months after RAI ablation. Clinical outcomes evaluated included structural disease progression, biochemical disease progression, and overall survival. RESULTS: Sixty-three patients (33%) had a biochemical incomplete response while 129 (67%) had a structural incomplete response. Eleven to 156 months after evaluation of their responses (mean=70 months), patients with structural incomplete response were significantly more likely to have structural evidence of disease at final follow-up (37% vs. 17%, p=0.0004), structural progression (52% vs. 5%, p<0.001), biochemical progression (45% vs. 11%, p<0.001), and death from disease (38% vs. 0%, p<0.0001) than patients demonstrating a biochemical incomplete response. Overall survival was significantly better in patients with either a biochemical incomplete response or a loco-regional structural incomplete response than patients demonstrating a structural incomplete response with distant metastasis (Kaplan-Meier analysis, p<0.0001). CONCLUSIONS: A structural incomplete response to initial therapy is associated with significantly worse clinical outcome than a biochemical incomplete response to therapy.

Classical and follicular variant of papillary thyroid carcinoma: a comparative study on clinicopathologic features and long-term outcome.

INTRODUCTION: The follicular variant of papillary thyroid carcinoma (FVPTC) is the most common histologic subtype of papillary thyroid carcinoma (PTC). However, it is still controversial whether FVPTC should behave differently from classical PTC (CPTC). The present study aimed at evaluating any potential difference in clinicopathologic features and long-term outcome of FVPTC as compared with CPTC. PATIENTS AND METHODS: Of 568 patients with PTC managed from 1973 to 2004, 308 were shown to have CPTC (54.2%) and 67 (11.8%) FVPTC after histologic review. The mean (+/- SD) follow-up period was 11.3 (+/- 8.9) years. The two groups were compared in terms of clinicopathological features, treatment received, and outcome regarding recurrence and disease-specific survival. RESULTS: There was no difference in age and gender ratio between the CPTC and FVPTC patients. Both groups had similar tumor characteristics in terms of tumor size, presence of multifocality, capsular invasion, lymphovascular permeation, and perineural infiltration. However, FVPTC patients had significantly fewer histologically confirmed cervical lymph node metastases (P = 0.027) and extrathyroidal involvement (P = 0.005). The proportion of bilateral resection, adjuvant radioactive iodine, and lymph node dissection did not differ significantly between the two groups. The FVPTC patients had a more favorable tumor risk by DeGroot classification (P = 0.003) and MACIS (Metastasis, Age, Completeness of excision, Invasiveness, and Size) score (P = 0.026). The 10- and 15-year actuarial disease-specific survivals did not differ significantly between FVPTC and CPTC patients (96.2% versus 90.7% and 96.2% versus 89.1%, respectively). CONCLUSIONS: Although patients with FVPTC had more favorable clinicopathologic features and a better tumor risk group profile, their long-term outcome was similar to that of CPTC patients.

Is there a place for thyroidectomy in older patients with thyrotoxic storm and cardiorespiratory failure?

Early thyroidectomy is the treatment of choice for thyrotoxic storm in patients with thyroid autonomy often induced by iodine. However, older patients who are mostly affected by this condition often have underlying chronic cardiopulmonary diseases, apparently contradicting surgical intervention. The published evidence for suitable treatment strategies in these patients is limited. We report the outcome of a series of older critically ill patients who were treated by thyroidectomy because of thyrotoxic storm. We retrospectively analyzed the outcome of 10 patients (4 males, 6 females; 70 years of age, range, 54-79, Burch-Wartofsky point scale, 61; range, 40-85) with thyrotoxic storm, thyroid autonomy, and severe cardiorespiratory and renal failure with cardiac arrhythmia, coronary artery or chronic obstructive pulmonary disease, or acute inflammation. Thyroidectomy was performed for the following reasons: symptoms of thyrotoxic storm deteriorated or did not improve within 24-48 hours despite intensive medical treatment, or patients developed thionamide-induced agranulocytosis or severe thrombocytopenia. All patients with severe accompanying diseases survived thyroidectomy (early post-operative mortality, 0%). The two oldest patients died 2-3 weeks after thyroidectomy because of myocardial infarction or respiratory failure (late postoperative mortality, 20%). In contrast, in the few previous reports of patients who underwent thyroidectomy for thyrotoxic storm and severe accompanying diseases (n = 7), late postoperative mortality was 43%. The overall mortality for all reported patients including our own, who underwent thyroidectomy for thyrotoxic storm with and without severe accompanying disease (n = 49) was 10%. Our results suggest that early total thyroidectomy should be considered as the method of choice for older, chronically ill patients with thyrotoxic storm complicated by cardiorespiratory and renal failure, especially if high-dose thionamide treatment, iopanoic acid, glucocorticoids, and intensive care fail to improve the patient's conditions within 12-24 hours.

[A diminishing number of thyroid operations in The Netherlands in 1972-1986]. / Dalend aantal schildklieroperaties in Nederland in de periode 1972-1986.

The numbers of thyroidectomies in The Netherlands decreased by 35% in the period 1972-1986. The decline started in 1977 and was the result of a decrease in the numbers of thyroidectomies for nontoxic diffuse and nodular goitre, and for toxic diffuse and nodular goitre. The numbers of thyroidectomies for malignant and benign thyroid neoplasms remained unchanged. These findings can be explained by a decrease of the indication for surgery in nontoxic nodular goitre due to the introduction of fine needle aspiration cytology and an increase of the application of radioactive iodine in the treatment of toxic diffuse and nodular goitre. The decrease of the number of thyroidectomies for nontoxic goitre in the younger age groups is suggestive of a lower prevalence due to the improvement of the iodine supplementation. The mean hospital stay for thyroidectomy decreased from 19.5 to 10.1 days. The hospital mortality rate after partial thyroidectomies decreased from 6.6% to 0.9%.