Differentiated Thyroid Cancer Presenting with Distant Metastases: A Population Analysis Over Two Decades

Goffredo, Paolo; Sosa, Julie Ann; Roman, Sanziana A.

doi:10.1007/s00268-013-2006-9

Cited by 62 publications

(61 citation statements)

References 26 publications

(32 reference statements)

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“…The incidence of distant metastasis at presentation in well-differentiated thyroid cancer is reportedly 1-4% [7,8]. In a recent comprehensive Surveillance, Epidemiology, and End Results (SEER) database study between 1988 and 2009, a total of 1291 patients with metastatic DTC at diagnosis were identified, amounting to a prevalence rate of 2.2% [9]. Patients with thyroid carcinoma typically present with a neck lump and distant metastatic disease may be diagnosed on the initial full-body workup or during follow-up, most commonly with the use of systemic radioactive iodine.…”

Section: Discussionmentioning

confidence: 99%

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma

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Iyer

Tan

et al. 2017

Eur Arch Otorhinolaryngol

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Thyroid carcinoma usually presents as a neck lump. Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma (WDTC) is rare and little is known about these patients. The aim of this study is to characterize patients who present with distant metastasis as the sole initial manifestation of WDTC. Retrospective review of case records of WDTC seen at the National Cancer Centre Singapore from 2002 to 2015 was performed. Patients with no prior complaint of neck swelling and whose first presentation was distant metastatic WDTC were included. Patient demographics, disease characteristics, radiological imaging, histopathology, types of treatment administered, and survival outcomes were examined. Nineteen out of seven hundred and thirty-two cases fulfilled inclusion criteria. Mean age was 65.4 years. All patients presented with osseous (36.8%), pulmonary (31.6%), cerebral metastases (5.3%), or a combination of two out of three aforementioned sites (26.3%). Follicular thyroid carcinoma was most common (47.4%), followed by papillary (36.8%) and medullary (15.8%). More than two-thirds of patients had multiple metastatic foci. Thirteen out of nineteen patients (68.4%) underwent total thyroidectomy with or without neck dissection and adjuvant RAI, while the rest declined surgery. The mean length of follow-up was 40.1 ± 5.1 months and 5-year disease-specific survival was 48.0 ± 17.2%. Distant metastasis without a history of neck swelling as the initial presentation of WDTC is extremely rare. Osseous metastasis and follicular thyroid carcinoma are the most common metastatic site and etiology, respectively. Disease-specific survival at 5-year post-diagnosis is lower compared to patients with thyroid carcinoma diagnosed with distant metastasis on further work-up.

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Section: Discussionmentioning

confidence: 99%

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma

See

Iyer

Tan

et al. 2017

Eur Arch Otorhinolaryngol

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“…Importantly, distant metastatic disease occurs in 2–7% of cases (22, 40, 41, 42) and should be treated aggressively. It is notable that all patients in our series underwent initial therapy including thyroidectomy and neck dissection, followed by 131 I ablation.…”

Section: Discussionmentioning

confidence: 99%

Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer

Kwong¹,

Marqusee²,

Gordon³

et al. 2014

Endocrine Connections

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Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metastatic disease was confirmed via tissue biopsy, abnormal PET scan, and/or biochemical elevations in thyroglobulin or antibody levels. Progression of disease was monitored clinically and with repeat imaging. We describe five patients with WDTC and pulmonary metastases, aged 8–43 years at diagnosis. All patients underwent initial surgery and radioactive iodine (RAI) ablation, with some receiving multiple treatments. Persistent pulmonary metastatic disease was confirmed over decades (mean 22 years, range 8–42 years) with minimal progression despite no further treatment beyond thyroid hormone suppression. Persistent disease was biopsy-proven in all patients at a mean of 9.6 years from last RAI treatment. All patients had elevated thyroglobulin or anti-thyroglobulin antibody levels, while three demonstrated metabolically active disease with positive FDG uptake on PET scan, and one patient with persistent radioactive iodine avid pulmonary metastasis 36 years after her last RAI treatment. This case series demonstrates that some patients with distant metastases, even if metabolically active and radioactive iodine resistant, remain stable for decades without further treatment. Clinical awareness of such patients and continual reassessment of disease risk following initial therapy are crucial as aggressive treatment may not be necessary.

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“…(DTC) is favorable, with the 10-y overall survival rate being around 90%, it can be life-threatening when distant metastasis occurs (2.2%-23% of DTC patients) (1,2). Serial treatment with radioiodine can render a 10-y survival rate of 42%, despite the fact that distant metastasis contributes most to death from DTC (3).…”

mentioning

confidence: 99%

TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer

Yang

et al. 2016

J Nucl Med

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Telomerase reverse transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT mutation in distant metastatic DTC and evaluated the correlation between TERT mutation and radioiodine uptake, as well as that between TERT mutation and therapy response. Methods: TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 patients with distant metastatic DTC. Stimulated thyroglobulin (sTg) changes, radioiodine uptake status (avid or nonavid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 mo (interquartile range, 29.0-70.5 mo), therapy response was classified as either disease control or refractory. Results: The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of the TERT mutation group. Of cases negative for both mutations, 78.12% (25/ 32) presented with decreased sTg. TERT mutation closely correlated with a poor response to radioiodine therapy (P , 0.001), and all 15 patients were classified as refractory to radioiodine therapy, with a positive predictive value of 100% at the endpoint of follow-up. TERT mutation was associated with older mean age at diagnosis (P , 0.001), larger mean tumor diameter (P 5 0.013), and greater likelihood of both BRAF mutation coexistence (P 5 0.044) and radioiodine-refractory character (P , 0.001). In the 36 cases whose imaging results underwent semiquantitative analysis, TERT mutation significantly correlated with non-radioiodine avidity, with a much lower mean tumor-to-background ratio (obtained from postradioiodine whole-body scanning) than in TERT wild-type cases (P , 0.001). In addition, patients with distant metastatic DTC with TERT mutation were more likely to lose radioiodine avidity at the initial radioiodine therapy than were those with only BRAF mutation (8/8 vs. 5/11; Fisher exact test, P 5 0.018). Conclusion: TERT mutation closely associates with non-radioiodine avidity in distant metastatic DTC, and when compared with BRAF mutation, TERT mutation manifested a greater negative influence on radioiodine uptake. TERT mutation could also be used as an early predictor of radioiodine-refractory cases.

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Differentiated Thyroid Cancer Presenting with Distant Metastases: A Population Analysis Over Two Decades

Abstract: Overall, met-DTC is uncommon. Given the lack of survival improvement observed over the last two decades, novel treatments should be pursued aggressively for this subset of patients.

Cited by 62 publications

References 26 publications

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma

Distant metastasis as the sole initial manifestation of well-differentiated thyroid carcinoma

Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer

TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer

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