scholarly journals Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1625
Author(s):  
Eman A. Toraih ◽  
Mohammad H. Hussein ◽  
Mourad Zerfaoui ◽  
Abdallah S. Attia ◽  
Assem Marzouk Ellythy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Distant Metastases ◽  
Multiple Organ ◽  
Organ Involvement ◽  
Papillary Thyroid ◽  
Cancer Specific Survival ◽  
Organ Metastasis

Introduction—heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods—patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results—from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan–Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17–2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40–2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13–25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93–5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50–28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21–21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15–2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20–8.07, p = 0.010). Conclusion—the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

scholarly journals MON-533 Diffuse Sclerosing Variant Papillary Thyroid Cancer: Clinical and Histopathological Features, Mutational Profile, Management and Outcome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Abeer Abdulhadi Aljomaiah ◽  
Yosra Moria ◽  
Nora Aldaej ◽  
Meshael Alswailem ◽  
Ali Saeed Alzahrani
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Molecular Genetics ◽  
Papillary Thyroid Cancer ◽  
Distant Metastases ◽  
The Other ◽  
Papillary Thyroid ◽  
Histopathological Features ◽  
Diffuse Sclerosing Variant

Abstract Diffuse sclerosing variant (DSV) is a rare subtype of papillary thyroid cancer (PTC). Whether it represents a higher grade subtype than conventional PTC is not quite clear. Furthermore, there are limited data on its long-term outcome and its molecular genetics. In this report, we studied all cases of DSV PTC seen at our center during the last 20 years. Out of more than 6000 patients (pts) with differentiated thyroid cancer, only 37 were DSV. We reviewed the clinical and histopathological features, management and outcome of these cases. In addition, molecular genetics is partially achieved; 17 out of these 37 cases have been genotyped for BRAFV600E, TERT promotor mutations, NRAS, HRAS and KRAS mutations. The molecular profiling of the other 20 cases is being done. A total of 37 pts were studied {(12 Males:25 Females, median age 21 years (8-89)}. One pt had lobectomy and the other 36 pts (97.3%) had a total thyroidectomy. Central only (4 pts) or central/lateral lymph node dissection (29 pts) were performed. The median tumor size was 4.5 cm (1.5-8.1). The tumor was multifocal in 27 cases (73%), with extrathyroidal invasion in 27 (73%) and lymphovascular invasion in 24 pts (64.8%). A background lymphocytic thyroiditis was present in 12 pts (32.4%). Lymph node metastases were present in 34 pts (92%) and distant metastases in 13 pts (35%). The sites of metastasis are lungs in 12 pts (32.4%) and lungs and bone in 1 pt. Twenty pts (54.1%) were in TNM8 stage 1, 10 pts (27%) in stage 2, 1 (2.7%) in stage 4a, 3 (8.1%) in stage 4b and 3 unstageable. The ATA risk classification for these pts was 4 pts (10.8%) in low, 12 (32.4%) in intermediate, 19 (51.4%) in high-risk groups and 2 could not be assessed. I-131 was administered to 33 pts (89.2%). The median administered activity was 136 mCi (46-218). Fifteen pts (40.5%) received additional therapies (3 surgeries, 7 RAI, 5 surgeries, and RAI). In 17 pts (46%) which were genotyped, only 3 tumors (8.1%) had BRAFV600E mutation, 1 (2.7%) had TERT promotor C228T mutation and none had RAS mutations. At the last follow up, 15 pts (40.5%) achieved an excellent response, 9 (24%) an indeterminate response, 6 (16.2%) with a structural disease, and 7 (19%) were lost for follow up. Conclusion: DSV PTC is a rare variant, occurs mostly in adolescent and young pts, characterized by aggressive histopathological features and high rates of lymph node and distant metastases but the commonly reported mutations in PTC are rare in DSV and mortality is absent.

scholarly journals Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3624
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Zeeshan Qadri ◽  
Khawar Siddiqui ◽  
Saif S. Al-Sobhi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hazard Rate ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Middle Eastern ◽  
Treatment Strategies ◽  
Recurrence Risk ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

scholarly journals Comprehensive Analysis of Prognostic Alternative Splicing Signature Reveals Recurrence Predictor for Papillary Thyroid Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mian Liu ◽  
Rooh Afza Khushbu ◽  
Pei Chen ◽  
Hui-Yu Hu ◽  
Neng Tang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Papillary Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
Cox Regression ◽  
Prognostic Biomarkers ◽  
Papillary Thyroid ◽  
Network Diagram ◽  
Prognostic Prediction

BackgroundAlternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC).MethodsAS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established.ResultsWe identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC.ConclusionThrough the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

scholarly journals A case of papillary thyroid cancer with soft tissue metastasis

2018 ◽  
Vol 5 (10) ◽  
pp. 3425 ◽  
Author(s):  
Jayan Stephen ◽  
Mebin B. Thomas ◽  
Mathew B. Thomas
Keyword(s):  
Thyroid Cancer ◽  
Soft Tissue ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid Cancer ◽  
Distant Metastases ◽  
Differentiated Thyroid Carcinoma ◽  
Metastatic Tumour ◽  
Papillary Thyroid ◽  
Soft Tissue Metastasis ◽  
Regional Lymph Nodes

Papillary thyroid cancer is the most common thyroid malignancy, and although metastatic spread is typically confined to regional lymph nodes, there are rare documented cases of distant spread of disease. Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases are extremely rare. Here we present an unusual case of soft tissue metastasis of papillary thyroid cancer to skeletal muscle. Soft tissue metastasis is rarely seen in differentiated thyroid carcinoma. Differentiated thyroid carcinoma, although generally clinically indolent, may occasionally develop distant metastases and even manifest itself as a metastatic tumour.

scholarly journals Nomogram-Based New Recurrence Predicting System in Early-Stage Papillary Thyroid Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yongfeng Ding ◽  
Zhuochao Mao ◽  
Jiaying Ruan ◽  
Xingyun Su ◽  
Linrong Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Cox Model ◽  
Staging System ◽  
Papillary Thyroid ◽  
Cox Regression Analysis ◽  
Ajcc Staging

Background and Objectives. The clinicopathological risk factors to predict recurrence of papillary thyroid cancer (PTC) patients remain controversial. Methods. PTC patients treated with thyroidectomy between January 1997 and December 2011 at the First Affiliated Hospital of Zhejiang University (Zhejiang cohort) were included. Multivariate Cox regression analysis was conducted to identify independent recurrence predictors. Then, the nomogram model for predicting probability of recurrence was built. Results. According to Zhejiang cohort (N = 1,697), we found that the 10-year event-free survival (EFS) rates of PTC patients with early-stage (TNM stages I, II, and III) were not well discriminated (91.6%, 89.0%, and 90.7%; P=0.768). The multivariate Cox model identified age, bilaterality, tumor size, and nodal status as independent risk factors for tumor recurrence in PTC patients with TNM stages I–III. We then developed a nomogram with the C-index 0.70 (95% CI, 0.64 to 0.76), which was significantly higher (P<0.0001) than the AJCC staging system (0.52). In the validation group, the C-index remained at a similar level. Conclusions. In this study, we build up a new recurrence predicting system and establish a nomogram for early-stage PTC patients. This prognostic model may better predict individualized outcomes and conduct personalized treatments.

Downregulation of miR-519d-3p is Associated with Poor Outcomes and Facilitates Tumor Progression in Papillary Thyroid Cancer by Regulating FOXQ1

2021 ◽  
Vol 53 (09) ◽  
pp. 625-632
Author(s):  
Pihong Li ◽  
Xiaoyu Pan ◽  
Zhouci Zheng ◽  
Yihan Sun ◽  
Yifan Han ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Progression ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Biological Effects ◽  
Pearson Correlation ◽  
Progression Free Survival ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid

AbstractMicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan–Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.

Predictive impact of metastatic lymph node burden on distant metastasis across papillary thyroid cancer variants

Thyroid ◽  
2021 ◽  
Author(s):  
Allen S. Ho ◽  
Michael Luu ◽  
Iram Shafqat ◽  
Jon Mallen-St. Clair ◽  
Michelle M Chen ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Papillary Thyroid Cancer ◽  
Distant Metastasis ◽  
Metastatic Lymph Node ◽  
Papillary Thyroid ◽  
Metastatic Lymph

scholarly journals Blood-Rich Enhancement in Ultrasonography Predicts Worse Prognosis in Patients With Papillary Thyroid Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Luying Gao ◽  
Xuehua Xi ◽  
Qiong Gao ◽  
Jiajia Tang ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Papillary Thyroid ◽  
Predictive Values ◽  
Incomplete Response ◽  
Potential Association ◽  
Contrast Enhanced ◽  
Patient Prognosis

Contrast-enhanced ultrasound (CEUS) can be used to evaluate microcirculation in cancers, which in turn is associated with the biologic features and ultimately patient prognosis. We conducted a retrospective analysis to examine potential association between CEUS parameters and prognosis in patients with papillary thyroid cancer (PTC). The analysis included 306 patients who underwent CEUS prior to thyroidectomy at our center during a period from 2012 to 2019. Subjects with excellent response (ER) were compared to the non-ER group (including indeterminate response, biochemical incomplete response and structural incomplete response). During the median follow-up of 34 months, ER was observed in 195 (63.7%) subjects. The remaining 111 (36.3%) patients developed non-ER events, with distant metastasis in five (1.6%) cases. In a multivariate COX regression, non-ER event was associated with the male sex (OR = 1.83, 95%CI: 1.21–2.76) and blood-rich enhancement in CEUS (OR = 1.69, 95%CI: 1.04–2.75). Based on this finding, we developed a predictive model: high risk for developing non-ER events was defined as having both risk factors; low risk was defined as having none or only one risk. In receiver operating characteristic (ROC) analysis, the area under the curve was 0.59 (95%CI: 0.52–0.66). The sensitivity and specificity were 17.1 and 95.4%, respectively. The positive and negative predictive values were 67.9 and 66.9%, respectively. In conclusion, blood-rich enhancement in CEUS is associated with non-ER events after thyroidectomy in patients with PTC.

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