Sarcopenia Increases the Risk of Major Organ Invasion in Patients with Papillary Thyroid Cancer

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Download Full-text

Impact of lymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation in defining CND

Endocrine Related Cancer ◽

10.1530/erc-12-0309 ◽

2012 ◽

Vol 20 (1) ◽

pp. 13-22 ◽

Cited By ~ 27

Author(s):

Ali S Alzahrani ◽

Mingzhao Xing

Keyword(s):

Thyroid Cancer ◽

Neck Dissection ◽

Papillary Thyroid Cancer ◽

Tertiary Care ◽

Disease Recurrence ◽

Central Neck Dissection ◽

Central Neck ◽

Papillary Thyroid ◽

Cervical Lymph Nodes ◽

The Impact

The impact of metastasized cervical lymph nodes (CLN) identified on central neck dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC) and the extent of CND needed to reduce recurrence/persistence have not been firmly established. To assess the impact of CLN metastasis andBRAFmutation on the recurrence/persistence of PTC and the potential ofBRAFmutation in assisting CND. Analyses of 379 consecutive patients with PTC who underwent thyroidectomy with (n=243) or without CND (n=136) at a tertiary-care academic hospital during the period 2001–2010 for their clinicopathological outcomes andBRAFmutation status. Increasingly aggressive tumor characteristics were found as the extent of CND was advanced following conventional risk criteria from non-CND to limited CND to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to 15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An increasing rate ofBRAFmutation was also found from less to more extensive CND. A strong association of CLN metastasis andBRAFmutation with disease recurrence/persistence was revealed on Kaplan–Meier analysis andBRAFmutation strongly predicted CLN metastasis. CLN metastases found on CND are closely associated with disease recurrence/persistence of PTC, which are both strongly predicted byBRAFmutation. Current selection of PTC patients for CND is appropriate but higher extent of the procedure, once selected, is needed to reduce disease recurrence, which may be defined by combination use of preoperativeBRAFmutation testing and conventional risk factors of PTC.

Download Full-text

The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

10.21203/rs.3.rs-35309/v4 ◽

2020 ◽

Author(s):

Krzysztof Kaliszewski ◽

Dorota Diakowska ◽

Łukasz Nowak ◽

Beata Wojtczak ◽

Jerzy Rudnicki

Keyword(s):

Thyroid Cancer ◽

Clinical Practice ◽

Risk Stratification ◽

Papillary Thyroid Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Papillary Thyroid ◽

Locally Advanced Disease ◽

In Series ◽

8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

Download Full-text

The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

10.21203/rs.3.rs-35309/v3 ◽

2020 ◽

Author(s):

Krzysztof Kaliszewski ◽

Dorota Diakowska ◽

Łukasz Nowak ◽

Beata Wojtczak ◽

Jerzy Rudnicki

Keyword(s):

Thyroid Cancer ◽

Clinical Practice ◽

Risk Stratification ◽

Papillary Thyroid Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Papillary Thyroid ◽

Locally Advanced Disease ◽

In Series ◽

8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

Download Full-text

The Age Threshold of the 8th Edition AJCC ClassificationIs Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

10.21203/rs.3.rs-35309/v2 ◽

2020 ◽

Author(s):

Krzysztof Kaliszewski ◽

Dorota Diakowska ◽

Łukasz Nowak ◽

Beata Wojtczak ◽

Jerzy Rudnicki

Keyword(s):

Thyroid Cancer ◽

Clinical Practice ◽

Risk Stratification ◽

Papillary Thyroid Cancer ◽

Advanced Disease ◽

Locally Advanced ◽

Papillary Thyroid ◽

Locally Advanced Disease ◽

In Series ◽

8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classificationis to increase the age cutoff for risk stratification in PTC from 45 to 55 years. However, whether this cutoff is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cutoff. In the first series (cutoff 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cutoff 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cutoff point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

Download Full-text

Surgical Treatment of Locally Advanced Papillary Thyroid Cancer

Thyroid and Parathyroid Diseases ◽

10.1007/978-3-319-78476-2_37 ◽

2018 ◽

pp. 239-244

Author(s):

Fatih Tunca

Keyword(s):

Thyroid Cancer ◽

Surgical Treatment ◽

Papillary Thyroid Cancer ◽

Locally Advanced ◽

Papillary Thyroid

Download Full-text

The Impact of Age and Gender on Papillary Thyroid Cancer Survival

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2011-2864 ◽

2012 ◽

Vol 97 (6) ◽

pp. E878-E887 ◽

Cited By ~ 96

Author(s):

J. Jonklaas ◽

G. Nogueras-Gonzalez ◽

M. Munsell ◽

D. Litofsky ◽

K. B. Ain ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Cancer Survival ◽

Papillary Thyroid ◽

Age And Gender ◽

And Gender ◽

The Impact

Download Full-text

Impact of Extent of Surgery on Survival for Papillary Thyroid Cancer Patients Younger Than 45 Years

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3039 ◽

2015 ◽

Vol 100 (1) ◽

pp. 115-121 ◽

Cited By ~ 50

Author(s):

Mohamed Abdelgadir Adam ◽

John Pura ◽

Paolo Goffredo ◽

Michaela A. Dinan ◽

Terry Hyslop ◽

...

Keyword(s):

Thyroid Cancer ◽

Total Thyroidectomy ◽

Papillary Thyroid Cancer ◽

Extent Of Resection ◽

Stage I ◽

Papillary Thyroid ◽

Cancer Data ◽

Thyroid Lobectomy ◽

Extent Of Surgery ◽

The Impact

Abstract Context: Papillary thyroid cancer (PTC) patients <45 years old are considered to have an excellent prognosis; however, current guidelines recommend total thyroidectomy for PTC tumors >1.0 cm, regardless of age. Objective: Our objective was to examine the impact of extent of surgery on overall survival (OS) in patients <45 years old with stage I PTC of 1.1 to 4.0 cm. Design, Setting, and Patients: Adult patients <45 years of age undergoing surgery for stage I PTC were identified from the National Cancer Data Base (NCDB, 1998–2006) and the Surveillance, Epidemiology, and End Results dataset (SEER, 1988–2006). Main Outcome Measure: Multivariable modeling was used to compare OS for patients undergoing total thyroidectomy vs lobectomy. Results: In total, 29 522 patients in NCDB (3151 lobectomy, 26 371 total thyroidectomy) and 13 510 in SEER (1379 lobectomy, 12 131 total thyroidectomy) were included. Compared with patients undergoing lobectomy, patients having total thyroidectomy more often had extrathyroidal and lymph node disease. At 14 years, unadjusted OS was equivalent between total thyroidectomy and lobectomy in both databases. After adjustment, OS was similar for total thyroidectomy compared with lobectomy across all patients with tumors of 1.1 to 4.0 cm (NCDB: hazard ratio = 1.45 [confidence interval = 0.88–2.51], P = 0.19; SEER: 0.95 (0.70–1.29), P = 0.75) and when stratified by tumor size: 1.1 to 2.0 cm (NCDB: 1.12 [0.50–2.51], P = 0.78; SEER: 0.95 [0.56–1.62], P = 0.86) and 2.1 to 4.0 cm (NCDB: 1.93 [0.88–4.23], P = 0.10; SEER: 0.94 [0.60–1.49], P = 0.80). Conclusions: After adjusting for patient and clinical characteristics, total thyroidectomy compared with thyroid lobectomy was not associated with improved survival for patients <45 years of age with stage I PTC of 1.1 to 4.0 cm. Additional clinical and pathologic factors should be considered when choosing extent of resection.

Download Full-text