scholarly journals Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

2021 ◽  
Vol 12 ◽  
Author(s):  
Cristiane J. Gomes-Lima ◽  
Leila Shobab ◽  
Di Wu ◽  
Dorina Ylli ◽  
Athanasios Bikas ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Tumor ◽  
Differentiated Thyroid Cancer ◽  
Distant Metastases ◽  
Molecular Profile ◽  
Mutation Burden ◽  
Genetic Landscape ◽  
Digital Microfluidic ◽  
Metastatic Sites ◽  
Promoter Mutations

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25–82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

scholarly journals Preoperative Serum Thyroglobulin and Its Correlation with the Burden and Extent of Differentiated Thyroid Cancer

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 625
Author(s):  
Hosu Kim ◽  
So Young Park ◽  
Jun-Ho Choe ◽  
Jee Soo Kim ◽  
Soo Yeon Hahn ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Tumor ◽  
Differentiated Thyroid Cancer ◽  
Medical Center ◽  
Distant Metastases ◽  
Predictive Biomarker ◽  
Tumor Burden ◽  
Serum Thyroglobulin ◽  
Preoperative Serum ◽  
Clinical Records

Lymph node metastasis (LNM) in differentiated thyroid cancer (DTC) is usually detected with preoperative ultrasonography; however, this has limited sensitivity for small metastases, and there is currently no predictive biomarker that can help to inform the extent of surgery required. We evaluated whether preoperative serum thyroglobulin levels can predict tumor burden and extent. We retrospectively reviewed the clinical records of 4029 DTC cases diagnosed and treated at a Samsung Medical Center between 1994 and 2016. We reviewed primary tumor size, number and location of LNM, and presence of distant metastases to reveal relationships between tumor burden and extent and preoperative serum thyroglobulin levels. We found a linear association between increasing preoperative thyroglobulin levels, the size of the primary tumor, and the number of LNM (r = 0.34, p < 0.001, r = 0.20, p < 0.001, respectively). Tumor extent also increased with each decile of increasing preoperative thyroglobulin level (r = 0.18, p < 0.001). Preoperative thyroglobulin levels of 13.15 ng/mL, 30.05 ng/mL, and 62.9 ng/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. Our results suggest that preoperative measurement of serum thyroglobulin may help to predict LNM and help to tailor surgery.

MOLECULAR PROFILE AND CLINICAL OUTCOMES IN DIFFERENTIATED THYROID CANCER PATIENTS PRESENTING WITH BONE METASTASIS

2019 ◽  
Vol 25 (12) ◽  
pp. 1255-1262 ◽  
Author(s):  
Nilma Malik ◽  
Alyaksandr V. Nikitski ◽  
Elie Klam ◽  
Jason Hunt ◽  
Benjamin Witt ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastasis ◽  
Primary Tumor ◽  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Radioiodine Therapy ◽  
Molecular Profile ◽  
Follicular Variant ◽  
Primary Tumor Size ◽  
Ras Gtpase

Objective: Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Methods: Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. Results: These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase ( TERT) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring TERT and RAS GTPase gene ( RAS) mutations, 2 had isolated TERT mutations, and 1 had TERT and proto-oncogene B-Raf ( BRAF) V600E mutations, respectively. Tumors carrying RAS, TERT, or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored BRAF and TERT mutations. Conclusion: These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of TERT mutations, frequently coexisting with RAS mutations. This molecular signature may predict a favorable response to radioiodine therapy. Abbreviations: BRAF = proto-oncogene B-Raf; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; FV = follicular variant; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; RAS = Ras GTPase gene; TERT = telomerase reverse transcriptase; TG = thyroglobulin

scholarly journals Metastatic site discriminates survival benefit of primary surgery for differentiated thyroid cancer with distant metastases: A real-world observational study

2020 ◽  
Author(s):  
WU DING ◽  
Guodong Ruan ◽  
Jianming zhu ◽  
Chuanjian Tu ◽  
Zhian Li
Keyword(s):  
Thyroid Cancer ◽  
Survival Benefit ◽  
Differentiated Thyroid Cancer ◽  
Distant Metastases ◽  
Metastatic Site ◽  
Primary Surgery ◽  
Surgery Group ◽  
Survival Difference ◽  
Clinicopathologic Factors ◽  
Metastatic Sites

Abstract Background: Role of surgery in the management of differentiated thyroid cancer (DTC) with distant metastases (DM) remains controversial. We aimed to determine the survival benefit of primary surgery on the basis of metastatic site. Methods: A retrospective cohort study based on the SEER database was conducted to identify DTC patients with DM diagnosed between 2010 and 2016. Patients were divided into surgery and non-surgery group, and propensity score weighting was used to balance clinicopathologic factors between groups. Results: Of 3537 DTC patients with DM, 956 (66.0%) cases were managed with surgery and 493 (34.0%) cases were managed without surgery. There were 798 all-cause deaths and 704 DTC specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 55.2%, compared to 27.8% (P < 0.001) for the non-surgery group. The magnitude of the survival difference with surgery was significantly correlated with metastatic sites (Pinteraction<0.001). Significant survival improvements in surgery group compared with non-surgery group were observed in patients with lung-only metastasis (adjusted HR = 0.45, P < 0.001) , bone-only metastasis (adjusted HR = 0.40, P < 0.001), or liver-only metastasis (adjusted HR = 0.27, P < 0.001), whereas survival no improvement of surgery was found for patients with brain-only metastasis (adjusted HR = 0.57, P = 0.059) or multiply organs distant metastases (adjusted HR = 0.81, P = 0.099). Conclusion: The survival benefit offered by surgery for DTC patients with DM varies by metastatic sites. Decisions for primary surgery of DTC patients with DM should be tailored according to metastatic sites.

scholarly journals A Search for Causes of Rising Incidence of Differentiated Thyroid Cancer in Children and Adolescents after Chernobyl and Fukushima: Comparison of the Clinical Features and Their Relevance for Treatment and Prognosis

2021 ◽  
Vol 18 (7) ◽  
pp. 3444
Author(s):  
Valentina Drozd ◽  
Vladimir Saenko ◽  
Daniel I. Branovan ◽  
Kate Brown ◽  
Shunichi Yamashita ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Children And Adolescents ◽  
Differentiated Thyroid Cancer ◽  
Age Groups ◽  
Distant Metastases ◽  
Lifestyle Changes ◽  
Radiation Doses ◽  
Related Factors ◽  
Fukushima Accident ◽  
Tumor Stages

The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4–5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.

scholarly journals Late-onset distant metastases confer poor prognosis in patients with well-differentiated thyroid cancer

Gland Surgery ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1857-1866
Author(s):  
Chan Kwon Jung ◽  
Sohee Lee ◽  
Ja Seong Bae ◽  
Dong-Jun Lim
Keyword(s):  
Thyroid Cancer ◽  
Poor Prognosis ◽  
Differentiated Thyroid Cancer ◽  
Late Onset ◽  
Distant Metastases ◽  
Well Differentiated

scholarly journals Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000–2010

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
I. Rachinsky ◽  
M. Rajaraman ◽  
W. D. Leslie ◽  
A. Zahedi ◽  
C. Jefford ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Distant Metastases ◽  
Tnm Staging ◽  
Remnant Ablation ◽  
Thyroid Hormone Withdrawal ◽  
Care Patterns ◽  
Major Variation ◽  
Well Differentiated ◽  
Over Time

Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada.Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation.Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20–85% for T1, 44–100% for T2, 58–100% for T3, and 59–100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation.Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time.

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