scholarly journals MON-502 Clinical-Pathological and Molecular Prognostic Markers in Aggressive and Poorly Differentiated Thyroid Cancers; A Tertiary-Center Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Suhaib Radi ◽  
Sabin Filimon ◽  
Michael Tamilia
Keyword(s):  
Thyroid Cancer ◽  
Vascular Invasion ◽  
Prognostic Markers ◽  
Recurrent Disease ◽  
Primary Therapy ◽  
Tumor Involvement ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

Abstract Background: Aggressive variants of papillary thyroid cancer (AV-PTC) and poorly differentiated thyroid cancers (PDTC) are 2 malignancies that lie in between the well-differentiated and the undifferentiated anaplastic cancers. While management of those well-differentiated cancers is established in the literature, that of AV-PTC and PDTC is less clear as they behave different to their more benign counterparts. The aim of this study is to describe the clinico-pathologic characteristics and genotypic background of AV-PTC and PDTC and to assess their prognostic value. Methods: The charts of all patients with thyroid cancer in our center for the last 10 years were retrospectively reviewed. Those with AV-PTC and PDTC were selected and included in the analysis. Clinical presentation, pathologic characteristics, molecular markers, specific treatments and clinical outcomes were compared among groups. Results: Out of 3244 thyroid cancer charts reviewed, 87 patients met the criteria for AV-PTC (n=45) and PDTC (n=42). Mean age at diagnosis was 48.1 years (SD 17.8), with female predominance (64.4% vs 35.6%). Median duration of follow up was 3 years (0.1-30). Out of the 75 patients with follow up for more than a year, 42.7% had either persistent disease or recurrence (52.6% in AV-PTC and 32.4% in PDTC) and 4.1% died. Presence of vascular invasion was associated with higher rates of persistent or recurrent disease (74.1% in positive vascular invasion vs 20.5% in negative vascular invasion, p < 0.001). Recurrence rate was 0% in patients with Ki67 < 10% and 40% in those >= 10%. There was no difference in terms of recurrence based on presence of BRAF mutation (33% in BRAF+ & 29% in BRAF-, p=1), or percentage of aggressive/poorly differentiated tumor involvement (48% in > 30% involvement vs 28% in < 30%, p = 0.132). Discussion and conclusion: The prevalence of AV-PTC and PDTC in this cohort was low at 1.3% each, and the rate of patients with persistent or recurrent disease at 1 year after primary therapy was also similar to that reported (42.7%). The mortality rates, however, in our study is surprisingly lower than that expected elsewhere (4.1%), most likely attributed to a shorter follow up period. Patients with absent vascular invasion were less likely to have persistent or recurrent disease. Those with lower Ki67 (<10%) also had lower relapse rate, although, the p value was > 0.05. It is worth mentioning that even though there were higher rates of recurrence among those with > 30% tumor involvement, it did not reach statistical significance, supporting recent studies stating that even tumor involvement of > 10% can have adverse outcomes. In conclusion, AV-PTC and PDTC are relatively rare but aggressive tumors. Possible prognostic markers that can be used to guide therapy and monitoring include: vascular invasion, extra-thyroidal extension, response to primary therapy and the proliferative index Ki67.

scholarly journals Therapeutic Outcomes of Recurrent Well-Differentiated Thyroid Carcinomas

2019 ◽  
Vol 104 (7-8) ◽  
pp. 304-313
Author(s):  
Chih-Yiu Tsai ◽  
Shu-Fu Lin ◽  
Szu-Tah Chen ◽  
Chuen Hsueh ◽  
Yann Sheng Lin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Recurrent Disease ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Carcinomas ◽  
Specific Mortality ◽  
Disease Specific Mortality ◽  
Well Differentiated ◽  
Disease Specific

Objective The aim of this study was to evaluate outcomes of the recurrent and non-recurrent groups including disease-specific mortality of patients with well-differentiated thyroid carcinoma after multimodality treatment. In addition, prognostic factors for disease-specific mortality were analyzed. Summary of Background Data Among 2,844, there were 166 patients with recurrent disease. Recurrent disease was defined as the presence of papillary or follicular thyroid cancer 6 months after the initial thyroidectomy, including locoregional or distant metastasis, diagnosed using diagnostic or therapeutic 131I scans or other imaging techniques. Methods The study was a retrospective analysis of prospectively collected data for a long-term follow-up result of well-differentiated thyroid carcinoma patients. Results The mean age of 166 patients was 45.8 ± 1.2 years, 116 (69.9%) were women, 111 (66.9%) had locoregional neck recurrence, and 55 (33.1%) had metastatic recurrence in distant organs. We found that when recurrences were observed, more than half were detected within the first 5 years following the initial therapy. The longest period of time before relapse was 29.8 years. After a mean follow-up period of 12.7 ± 0.5 years, 37 (22.3%) patients experienced disease-specific mortality. Multivariable analysis revealed that older age, male sex, and development of a second primary malignancy were associated with disease-specific mortality. Higher post-operative levels of thyroglobulin predicted a shorter time to relapse. Conclusions These data indicate that among the recurrent cases over 50% of recurrent well-differentiated thyroid carcinomas were diagnosed within 5 years after initial thyroidectomy. Additionally, more than 20% of the patients died of thyroid cancer.

scholarly journals Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

2016 ◽  
Vol 23 (4) ◽  
pp. R185-R205 ◽  
Author(s):  
David Viola ◽  
Laura Valerio ◽  
Eleonora Molinaro ◽  
Laura Agate ◽  
Valeria Bottici ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Survival Rates ◽  
Current Status ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

AbstractThyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15–20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

scholarly journals Shifting Paradigms and Debates in the Management of Well-differentiated Thyroid Cancer

2009 ◽  
Vol 1 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Ashok R Shaha
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Central Compartment ◽  
The United States ◽  
The Past ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Radioactive Iodine Ablation

ABSTRACT The incidence of thyroid cancer has almost quadrupled over the past 30 years in the United States, a large number of which are less than 2 cm in size. There have been several paradigms in the management of well-differentiated thyroid cancer. The common debate in the past was total vs less than total thyroidectomy, however recently there is more interest in evaluation of fine needle aspiration of thyroid nodules, and intraoperative management in relation to the central compartment. The debate about elective central compartment nodal dissection vs observation has generated considerable controversy in the recent literature. Postoperative follow-up with thyroglobulin and ultrasound has become the mainstay of postoperative evaluation. Radioactive iodine ablation has been used in selected patients with advanced or aggressive thyroid cancer. While risk stratification continues to be an important facet in the evaluation of thyroid cancer, low risk patients are rarely offered radioactive iodine ablation. Understanding of the details of the histopathology is crucial, especially dividing the patients between well-differentiated and poorly differentiated thyroid cancer. PET scanning has been useful in the follow-up of patients with poorly differentiated, insular or tall cell thyroid cancer. External radiation therapy is used in selected patients where gross residual disease was present or there are painful bony metastases. Considerable research has been undertaken to identify specific molecular markers and their applicability for targeted therapy. This manuscript describes the current debates and shifting paradigms in the management of well-differentiated thyroid cancer.

scholarly journals Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

2021 ◽  
Vol 22 (6) ◽  
pp. 3117
Author(s):  
Loredana Lorusso ◽  
Virginia Cappagli ◽  
Laura Valerio ◽  
Carlotta Giani ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Approved Drugs ◽  
New Generation ◽  
Systemic Therapies

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.

scholarly journals What is New on Thyroid Cancer Biomarkers

2008 ◽  
Vol 3 ◽  
pp. BMI.S669 ◽  
Author(s):  
Rosaria M. Ruggeri ◽  
Alfredo Campennì ◽  
Sergio Baldari ◽  
Francesco Trimarchi ◽  
Maria Trovato
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Follicular Epithelium ◽  
Routine Practice ◽  
Appropriate Treatment ◽  
Follicular Lesions ◽  
Needle Aspiration Cytology ◽  
Well Differentiated

Thyroid cancer harbours in about 5% of thyroid nodules. The majority of them are well-differentiated cancers originating from the follicular epithelium, and are subdivided into papillary and follicular carcinomas. Undifferentiated carcinomas and medullary thyroid carcinomas arising from C cells are less common. Although most thyroid nodules are benign, distinguishing thyroid cancer from benign lesions is crucial for an appropriate treatment and follow-up. The fine needle aspiration cytology (FNAC) allows the diagnosis of nature of thyroid nodules in the majority of cases. However, FNAC has some limitations, particularly in the presence of follicular lesions which can appear dubious in rare instances even at histology. In an effort to improve diagnostic accuracy and offer new prognostic criteria, several immunohistochemical and molecular markers have been proposed. However, most of them have to be validated on large series before being used in routine practice.

scholarly journals Factors affecting overall survival in ductal adenocarcinoma of the pancreatic head. Experience of one center

2021 ◽  
Vol 11 (1) ◽  
pp. 20-28
Author(s):  
D.  M. Kuchin ◽  
Ya.  I. Kolesnik ◽  
H.  G. Torgomyan ◽  
V.  E. Zagainov
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Vascular Invasion ◽  
Survival Rates ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Factors Affecting ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Major Factors

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.

scholarly journals Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

2014 ◽  
Vol 21 (3) ◽  
pp. 405-414 ◽  
Author(s):  
Noriko Kimura ◽  
Ryoichi Takayanagi ◽  
Nae Takizawa ◽  
Eiji Itagaki ◽  
Takayuki Katabami ◽  
...  
Keyword(s):  
Vascular Invasion ◽  
Significant Negative Correlation ◽  
Initial Operation ◽  
Dehydrogenase Gene ◽  
Prediction Of Metastasis ◽  
Poorly Differentiated ◽  
The Mean ◽  
Well Differentiated ◽  
Benign Tumours ◽  
Subunit B

Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10–30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0–2 points), moderately differentiated (MD, 3–6 points) and poorly differentiated (PD, 7–10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08±0.17 and 5.33±0.43 (mean±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=−0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5±2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.

Significance of morphometric, DNA cytometric features, and other prognostic markers on survival of endometrial cancer patients in northern Norway

2002 ◽  
Vol 12 (1) ◽  
pp. 49-56 ◽  
Author(s):  
A Ørbo ◽  
M Rydningen ◽  
B Straume ◽  
S Lysne
Keyword(s):  
Endometrial Cancer ◽  
Cancer Patients ◽  
Vascular Invasion ◽  
Prognostic Markers ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
Figo Stage ◽  
Stage I ◽  
Northern Norway

Abstract.Ørbo A, Rydningen M, Straume B, Lysne S. Significance of morphometric, DNA cytometric features, and other prognostic markers on survival of endometrial cancer patients in northern Norway.The objective of this study was to evaluate the prognostic value of nuclear morphometric features and DNA ploidy by flow cytometry next to depth of myometrial invasion and vascular invasion in endometrial cancer of all FIGO stages.A total of 123 women (103 FIGO stage I, eight stage II, and 12 stage III and IV) from northern Norway were studied. The follow-up period was between 7 and 19 years. The median age of patients was 62 years. The primary surgery was performed in the University Hospital of Tromsø or in the seven different reference hospitals in the northern part of Norway after an endometrial cancer diagnosis. The histologic, morphometric, flowcytometric and immunohistochemical investigations were based on archival paraffin-embedded material. The information regarding the follow-up data and clinical information were obtained from the medical records.Thirteen (10.6%) patients from the entire group (all stages) but only three (2.7%) of the FIGO stage I and II patients died from locally recurrent or metastatic disease. FIGO substage (P = 0.0006; odds ratio [OR] = 16.44, 95% confidence interval [CI] = 3.36–80.45), vascular invasion (P = 0.01, OR = 6.42, CI = 1.57–26.34) and nuclear size (P = 0.025, 0 R = 1.3, CI = 1.05–1.61) were independently correlated with recurrence in a multivariate analysis but histologic grade and DNA ploidy were not. Vascular invasion was poorly reproducible both between and within the same observer, however.In this retrospective study of all stages of endometrial carcinoma with long follow-up periods the primary tumor characteristics nuclear perimeter and FIGO stage were of prognostic significance in addition to the poorly reproducible vessel invasion.

scholarly journals Management of differentiated thyroid cancer diagnosed during pregnancy

1999 ◽  
pp. 404-406 ◽  
Author(s):  
L Vini ◽  
S Hyer ◽  
B Pratt ◽  
C Harmer
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Differentiated Thyroid Cancer ◽  
Subtotal Thyroidectomy ◽  
Second Trimester ◽  
Original Cohort ◽  
Well Differentiated ◽  
Disease Free ◽  
In Pregnancy

OBJECTIVE: To assess the outcome of thyroid cancer diagnosed during pregnancy. DESIGN: Retrospective analysis of patients diagnosed between 1949 and 1997 with thyroid cancer presenting during pregnancy. RESULTS: Nine women with a median age of 28 years were identified. A thyroid nodule was discovered by the clinician during routine antenatal examination in four cases, the remainder had noted a lump in the neck. In all patients, the nodule was reported to almost double in size during the pregnancy. One patient underwent subtotal thyroidectomy during the second trimester; eight were operated on within 3 to 10 months from delivery. Total thyroidectomy was performed in five and subtotal thyroidectomy in four. All tumours were well differentiated and ranged in size from 1 to 6 cm. OUTCOME: The median follow-up was 14 years (5-31 years). One patient relapsed locally requiring further surgery. One patient developed bone metastases dying 7 years after presentation; her planned treatment had been delayed because of an intervening pregnancy. Eight of the original cohort of patients are currently disease free. CONCLUSIONS: Differentiated thyroid cancer presenting in pregnancy generally has an excellent prognosis. When the disease is discovered early in pregnancy, surgery should be considered in the second trimester but radioiodine scans and treatment can be safely delayed until after delivery. In all cases, treatment should not be delayed for more than a year.

scholarly journals What's New in Molecular Targeted Therapies for Thyroid Cancer?

2021 ◽  
Vol 37 (2) ◽  
pp. 1-9
Author(s):  
Seonyoung Min ◽  
Hyunseok Kang
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Radioactive Iodine ◽  
Checkpoint Inhibitors ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Thyroid Cancers ◽  
Ret Mutation ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

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