Publications by authors named "Jolanta Krajewska"

79 Publications

Childhood thyroid carcinoma – an experience of one center.

Endokrynol Pol 2021 Oct 14. Epub 2021 Oct 14.

Department of Pediatrics, Endocrinology, Diabetology with a Cardiology Division, Medical University of Bialystok, Polska.

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http://dx.doi.org/10.5603/EP.a2021.0086DOI Listing
October 2021

Thyroid nodules with indeterminate cytopathology: a constant challenge in everyday practice. The effectiveness of clinical decisions using diagnostic tools available in Poland.

Pol Arch Intern Med 2021 Oct 11. Epub 2021 Oct 11.

Introduction: A crucial issue in the management of thyroid nodules is to estimate, as accurately as possible, the malignancy risk in thyroid lesions. The key tool for risk stratification is fine needle aspiration biopsy. Unfortunately, approximately 20 % of biopsy results are indeterminate. The malignancy risk assigned to these categories does not allow unequivocal further management.

Objectives: We aimed to assess the malignancy risk in indeterminate thyroid nodules in the Polish population, and to analyze the effectiveness of clinical decisions after an indeterminate cytological diagnosis in Polish clinical practice.

Patients And Methods: The retrospective analysis included 222 indeterminate thyroid nodules in 222 patients. The ultrasound features were assessed from scans preceding a thyroid biopsy. Cytology results were classified according to the Bethesda system. The nature of the thyroid nodule was determined on the basis of a histopathological analysis or follow up.

Results: The analyzed cohort included 82 lesions in Bethesda category III, 75 in Bethesda category IV and 65 in Bethesda category V. The malignancy risk, estimated on the basis of histological verification and surveillance was 6.7% for Bethesda III, 11.3% for Bethesda IV and 70.3%for Bethesda V category. An ultrasound pattern was not effective enough for refining the malignancy risk after obtaining an indeterminate cytopathology result. In the case of surgery, postoperative hypoparathyroidism was significantly more frequent following more extensive surgical procedures.

Conclusions: Majority of Polish patients with thyroid nodules assigned to cytological categories Bethesda III and IV is overtreated using diagnostic tools currently available in Poland.
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http://dx.doi.org/10.20452/pamw.16117DOI Listing
October 2021

Therapeutic Strategy in Low-Risk Papillary Thyroid Carcinoma - Long-Term Results of the First Single-Center Prospective Non-Randomized Trial Between 2011 and 2015.

Front Endocrinol (Lausanne) 2021 6;12:718833. Epub 2021 Sep 6.

Department of Nuclear Medicine and Endocrine Oncology, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country. A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-up.

Material: Our prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed.

Results: Only 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7 edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism.

Summary: The results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient.
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http://dx.doi.org/10.3389/fendo.2021.718833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450606PMC
September 2021

Stereotactic radiotherapy is a useful treatment option for patients with medullary thyroid cancer.

BMC Endocr Disord 2021 Aug 9;21(1):160. Epub 2021 Aug 9.

Nuclear Medicine and Endocrine Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Wybrzeze AK 15, 44-101 , Gliwice, Poland.

The role of radiotherapy in advanced medullary thyroid carcinoma (MTC) is confined to patients in whom surgical treatment or the administration of tyrosine kinase inhibitors are not possible or contraindicated. High fractionated radiation doses during radiosurgery or fractionated stereotactic radiotherapy are applied to reduce cancer-related symptoms and stabilize irradiated lesions. This study aimed to retrospectively evaluate the therapeutic effect of stereotactic radiotherapy in MTC patients.

Material And Methods: The study group involved 11 MTC patients, treated due to 16 cancer lesions, mainly bone metastases (10 lesions), lymph node (2 lesions) metastases, or liver metastases (2 lesions), one primary thyroid tumor, and one MTC recurrence in the thyroid bed. The fractionated and total radiation doses ranged between 5 and 12 Gy and 8-44 Gy, respectively. Six lesions were treated with a single radiation fraction, three lesions with 2 fractions, another 6 lesions with 3 fractions, whereas the remaining one metastatic lesion with 9 fractions of stereotactic radiosurgery.

Results: The beneficial effect of stereotactic radiosurgery was obtained in all treated lesions. None of treated lesions progressed in the further disease course. Fourteen lesions were stable (87.5 %), including eight lesions showing progression before radiosurgery (good response). Disease control was obtained in all soft-tissue metastases. Regarding bone metastases, partial regression was achieved in 20 % lesions, whereas in 30 % lesions progressive before radiotherapy, the treatment led to disease stabilization.

Conclusions: Our data pointed to the effectiveness of high-dose fractionated radiotherapy in MTC. However, an observation of a larger group of patients is required to confirm it.
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http://dx.doi.org/10.1186/s12902-021-00832-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353818PMC
August 2021

Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Oncol 2021 08 5;22(8):1126-1138. Epub 2021 Jul 5.

Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Patients with radioiodine-refractory differentiated thyroid cancer (DTC) previously treated with vascular endothelial growth factor receptor (VEGFR)-targeted therapy have aggressive disease and no available standard of care. The aim of this study was to evaluate the tyrosine kinase inhibitor cabozantinib in this patient population.

Methods: In this global, randomised, double-blind, placebo-controlled, phase 3 trial, patients aged 16 years and older with radioiodine-refractory DTC (papillary or follicular and their variants) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to oral cabozantinib (60 mg once daily) or matching placebo, stratified by previous lenvatinib treatment and age. The randomisation scheme used stratified permuted blocks of block size six and an interactive voice-web response system; both patients and investigators were masked to study treatment. Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors. Patients receiving placebo could cross over to open-label cabozantinib on disease progression confirmed by blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (confirmed response per Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population) and progression-free survival (time to earlier of disease progression per RECIST version 1.1 or death) in all patients (intention-to-treat [ITT] population), both assessed by BIRC. This report presents the primary objective response rate analysis and a concurrent preplanned interim progression-free survival analysis. The study is registered with ClinicalTrials.gov, NCT03690388, and is no longer enrolling patients.

Findings: Between Feb 27, 2019, and Aug 18, 2020, 227 patients were assessed for eligibility, of whom 187 were enrolled from 164 clinics in 25 countries and randomly assigned to cabozantinib (n=125) or placebo (n=62). At data cutoff (Aug 19, 2020) for the primary objective response rate and interim progression-free survival analyses, median follow-up was 6·2 months (IQR 3·4-9·2) for the ITT population and 8·9 months (7·1-10·5) for the OITT population. An objective response in the OITT population was achieved in ten (15%; 99% CI 5·8-29·3) of 67 patients in the cabozantinib group versus 0 (0%; 0-14·8) of 33 in the placebo (p=0·028) but did not meet the prespecified significance level (α=0·01). At interim analysis, the primary endpoint of progression-free survival was met in the ITT population; cabozantinib showed significant improvement in progression-free survival over placebo: median not reached (96% CI 5·7-not estimable [NE]) versus 1·9 months (1·8-3·6); hazard ratio 0·22 (96% CI 0·13-0·36; p<0·0001). Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo, the most frequent of which were palmar-plantar erythrodysaesthesia (13 [10%] vs 0), hypertension (11 [9%] vs 2 [3%]), and fatigue (ten [8%] vs 0). Serious treatment-related adverse events occurred in 20 (16%) of 125 patients in the cabozantinib group and one (2%) of 62 in the placebo group. There were no treatment-related deaths.

Interpretation: Our results show that cabozantinib significantly prolongs progression-free survival and might provide a new treatment option for patients with radioiodine-refractory DTC who have no available standard of care.

Funding: Exelixis.
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http://dx.doi.org/10.1016/S1470-2045(21)00332-6DOI Listing
August 2021

Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival.

Front Endocrinol (Lausanne) 2020 6;11:571421. Epub 2020 Oct 6.

Department of Nuclear Medicine and Endocrine Oncology, M.Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

We are witnessing a rapid worldwide increase in the incidence of papillary thyroid carcinoma (PTC) in the last thirty years. Extensive implementation of cancer screening and wide availability of neck ultrasound or other imaging studies is the main reason responsible for this phenomenon. It resulted in a detection of a growing number of clinically asymptomatic PTCs, mainly low-risk tumors, without any beneficial impact on survival. An indolent nature of low-risk PTC, particularly papillary thyroid microcarcinoma (PTMC), and the excellent outcomes raise an ongoing discussion regarding the adequacy of treatment applied. The question of whether PTMC is overtreated or not is currently completed by another, whether PTMC requires any treatment. Current ATA guidelines propose less extensive preoperative diagnostics and, if differentiated thyroid cancer is diagnosed, less aggressive surgical approach and limit indications for postoperative radioiodine therapy. However, in intrathyroidal PTMCs in the absence of lymph node or distant metastases, active surveillance may constitute alternative management with a low progression rate of 1%-5% and without any increase in the risk of poorer outcomes related to delayed surgery in patients, in whom it was necessary. This review summarizes the current knowledge and future perspectives of active surveillance in low-risk PTC.
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http://dx.doi.org/10.3389/fendo.2020.571421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573306PMC
May 2021

Current status of the prognostic molecular markers in medullary thyroid carcinoma.

Endocr Connect 2020 Dec;9(12):R251-R263

Nuclear Medicine and Endocrine Oncology Department, M. Sklodowska-Curie Institute National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Medullary thyroid cancer (MTC) is a rare thyroid malignancy, which arises from parafollicular C-cells. It occurs in the hereditary or sporadic form. Hereditary type is a consequence of activation of the RET proto-oncogene by germline mutations, whereas about 80% of sporadic MTC tumors harbor somatic, mainly RET or rarely RAS mutations. According to the current ATA guidelines, a postoperative MTC risk stratification and long-term follow-up are mainly based on histopathological data, including tumor stage, the presence of lymph node and/or distant metastases (TNM classification), and serum concentration of two biomarkers: calcitonin (Ctn) and carcinoembryonic antigen (CEA). The type of RET germline mutation also correlates with MTC clinical characteristics. The most common and the best known RET mutation in sporadic MTC, localized at codon 918, is related to a more aggressive MTC course and poorer survival. However, even if histopathological or clinical features allow to predict a long-term prognosis, they are not sufficient to select the patients showing aggressive MTC courses requiring immediate treatment or those, who are refractory to different therapeutic methods. Besides the RET gene mutations, there are currently no other reliable molecular prognostic markers. This review summarizes the present data of genomic investigation on molecular prognostic factors in medullary thyroid cancer.
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http://dx.doi.org/10.1530/EC-20-0374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774764PMC
December 2020

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey.

Front Endocrinol (Lausanne) 2020 10;11:381. Epub 2020 Jul 10.

The International Fund "Help for Patients With Radiation-Induced Thyroid Cancer 'ARNICA"', Minsk, Belarus.

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case-control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial "misdiagnosis."
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http://dx.doi.org/10.3389/fendo.2020.00381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381297PMC
May 2021

Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma-Do They Exist?

Int J Mol Sci 2020 Jun 29;21(13). Epub 2020 Jun 29.

Nuclear Medicine and Endocrine Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-101 Gliwice, Poland.

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A-U133, set B-HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: (most significant) and . However, when analyzed on an independent dataset by qPCR, the gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.
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http://dx.doi.org/10.3390/ijms21134629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369779PMC
June 2020

Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma.

Cancers (Basel) 2020 Jun 17;12(6). Epub 2020 Jun 17.

Department of Genetic and Molecular Diagnostics of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-102 Gliwice, Poland.

Background: Telomerase reverse transcriptase promoter (p) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of p mutations in PTC was the aim of our study.

Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. V600E, and p mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(-) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis.

Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(-) PTCs. Deregulation of pathways involved in key cell processes was observed.

Conclusions: p mutations are related to higher PTC aggressiveness. gene was validated as associated with p mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.
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http://dx.doi.org/10.3390/cancers12061597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352936PMC
June 2020

Impact of the Tumor Microenvironment on the Gene Expression Profile in Papillary Thyroid Cancer.

Pathobiology 2020 22;87(2):143-154. Epub 2020 Apr 22.

Nuclear Medicine and Endocrine Oncology Department, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland.

Transcriptome of papillary thyroid cancer (PTC) is well characterized and correlates with some prognostic and genotypic factors, but data addressing the interaction between PTC and tumor microenvironment (TME) are scarce. Therefore, in the present study, we aimed to assess the impact of TME on gene expression profile in PTC. We evaluated the gene expression profile in PTC and normal thyroid cells isolated by laser capture microdissection and in whole tissue slides corresponding to the entire tumor. We included 26 microdissected samples for gene expression analysis (HG-U133 PLUS 2.0, Affymetrix, currently Thermo Fisher Scientific USA): 15 PTC samples, 11 samples of normal thyrocytes, and 30 whole slides (15 PTC and 15 normal thyroid). Transcripts were divided into three groups: differentially expressed both in microdissected and whole slides, transcripts differently expressed in microdissected samples and not changed in whole slides, and transcripts differentially expressed in whole slides and not changed in microdissected samples. Eleven genes were selected for validation in an independent set of samples; among them, four genes differentiated only microdissected PTC and normal cells. Two genes (PTCSC and CTGF) were confirmed. One gene (FOS) was not confirmed by the validation, whereas EGR1 was also significant in whole slide analysis. The other seven genes (TFF3, FN1, MPPED2, MET, KCNJ2, TACSTD2, and GALE) showed differentiated expression in microdissected thyrocytes and in whole tumor slides. Most of identified genes were related to the tumor-microenvironment interaction and confirmed the crosstalk between TME and cancer cells.
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http://dx.doi.org/10.1159/000507223DOI Listing
April 2021

European perspective on the use of molecular tests in the diagnosis and therapy of thyroid neoplasms.

Gland Surg 2020 Feb;9(Suppl 2):S69-S76

The Oncologic and Reconstructive Surgery Clinic, Maria Sklodowska-Curie Institute-Oncology Center, Gliwice Branch, Gliwice, Poland.

Thyroid nodules are frequently observed, particularly in individuals of over 60 years of age. On the other hand, most of the detected changes are benign and they do not require surgery. Therefore, differentiation between benign and malignant lesions in preoperative diagnosis is of crucial importance. Currently, the use of fine-needle aspiration biopsy (FNAB) and cytological assessment are the gold standard in the diagnosis of thyroid nodules. This procedure significantly reduces the need for diagnostic surgical intervention. However, approximately 15-30% of cytological results are classified as indeterminate. This is mainly due to the lack of specific cytomorphologic features that would facilitate the diagnosis based on cell evaluation under microscopic assessment. For the diagnoses of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), the assessment of invasion is crucial. Such an evaluation is not possible in cytology. Recently, molecular tests have been developed. They improve cytological diagnosis, particularly in the case of indeterminate results. Commercially available tests are developed based on the North American population. It is important to assess whether such tests can be used in the evaluation of e.g., European population.
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http://dx.doi.org/10.21037/gs.2019.10.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044080PMC
February 2020

The role of postoperative adjuvant radiotherapy in the local control in medullary thyroid carcinoma.

Endocr Connect 2019 Nov 1. Epub 2019 Nov 1.

B Jarzab, Nuclear Medicine and Endocrine Oncology Department, M.Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.

Background: The value of postoperative radiotherapy in the treatment of medullary thyroid carcinoma (MTC) has not been unequivocally demonstrated. Therefore our study aimed to answer the question of whether adjuvant radiotherapy showed any impact on the risk of local recurrence and whether there were any differences in response to radiotherapy between hereditary and sporadic MTC.

Methods: A retrospective analysis involved 254 MTC patients, among them 73 patients with a hereditary disease. Two hundred and twenty-four patients, including 43 persons at high risk of local relapse, underwent only initial surgery, 18 other patients were operated due to MTC recurrences, whereas the remaining 12 patients had cytoreductive procedure or were not amenable for surgery. Radiotherapy was carried out in 132 patients. One hundred and twenty patients underwent adjuvant radiotherapy, among them 102 patients after initial surgery. The median follow up was 10 years (range 0.5-29 years).

Results: Local recurrence occurred in 107/254 patients, among them in 63 subjects after prior radiotherapy. The frequency of relapse showed significant, increasing trend toward higher MTC stages (p<0.001). More relapses were noticed in patients with lymph node metastases at diagnosis. Adjuvant radiotherapy was associated with a lower risk of nodal recurrence only in high-risk patients, particularly if lymph node metastases were present at MTC diagnosis. The differences between hereditary and sporadic subgroups were not significant.

Conclusions: Adjuvant radiotherapy has a limited importance in MTC treatment. It should be considered in high-risk MTC patients. The presence of RET mutation does not influence the response to radiation.
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http://dx.doi.org/10.1530/EC-19-0387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933828PMC
November 2019

Postoperative Radioiodine Treatment within 9 Months from Diagnosis Significantly Reduces the Risk of Relapse in Low-Risk Differentiated Thyroid Carcinoma.

Nucl Med Mol Imaging 2019 Oct 5;53(5):320-327. Epub 2019 Sep 5.

Nuclear Medicine and Endocrine Oncology Department, M.Sklodowska-Curie Institute-Oncology Center, Gliwice Branch, Wybrzeze AK 15, 44-101 Gliwice, Poland.

Purpose: Although postoperative radioiodine (RAI) therapy has been used in patients with differentiated thyroid carcinoma (DTC) for many years, there is still lack of data defining the timing of RAI administration. A retrospective analysis was carried out to answer the question whether the time of postoperative RAI treatment demonstrated any impact on long-term outcomes, particularly in low-risk DTC.

Material: The analyzed group involved 701 DTC patients staged pT-TN-NM, who underwent total thyroidectomy and postoperative RAI therapy. According to the time interval between DTC diagnosis and RAI administration, patients were allocated to one of three groups: up to 9 months ( = 150), between 9 and 24 months ( = 323), and > 24 months ( = 228). Median follow-up was 12.1 years (1.5-15.2).

Results: Based on an initial DTC advancement and postoperative stimulated thyroglobulin concentration patients were stratified as a low-, intermediate-, and high-risk group. Low-risk patients, who received RAI therapy up to 9 months, demonstrated significantly lower risk of relapse comparing to those, in whom RAI was administered between 9 and 24 months and after 24 months since DTC diagnosis: 0%, 5.5%, and 7.1%, respectively. Regarding intermediate- and high-risk groups, the differences in the timing of postoperative RAI treatment were not significant.

Conclusion: If postoperative RAI treatment is considered in low-risk DTC, any delay in RAI administration above 9 months since diagnosis may be related to poorer long-term outcomes.
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http://dx.doi.org/10.1007/s13139-019-00608-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821904PMC
October 2019

Important considerations when choosing pharmacotherapy for Graves' disease in children.

Expert Opin Pharmacother 2019 10 5;20(14):1675-1677. Epub 2019 Jul 5.

Nuclear Medicine and Endocrine Oncology Department, Maria Sklodowska-Curie Institute - Oncology Center , Gliwice , Poland.

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http://dx.doi.org/10.1080/14656566.2019.1638365DOI Listing
October 2019

Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma.

Genes Chromosomes Cancer 2019 08 18;58(8):558-566. Epub 2019 Feb 18.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Center Gliwice Branch, Gliwice, Poland.

Papillary thyroid carcinoma (PTC) is most common among all thyroid cancers. Multiple genomic alterations occur in PTC, and gene rearrangements are one of them. Here we screened 14 tumors for novel fusion transcripts by RNA-Seq. Two samples harboring RET/PTC1 and RET/PTC3 rearrangements were positive controls whereas the remaining ones were negative regarding the common PTC alterations. We used Sanger sequencing to validate potential fusions. We detected 2 novel potentially oncogenic transcript fusions: TG-FGFR1 and TRIM33-NTRK1. We detected 4 novel fusion transcripts of unknown significance accompanying the TRIM33-NTRK1 fusion: ZSWIM5-TP53BP2, TAF4B-WDR1, ABI2-MTA3, and ARID1B-PSMA1. Apart from confirming the presence of RET/PTC1 and RET/PTC3 in positive control samples, we also detected known oncogenic fusion transcripts in remaining samples: TFG-NTRK1, ETV6-NTRK3, MKRN1-BRAF, EML4-ALK, and novel isoform of CCDC6-RET.
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http://dx.doi.org/10.1002/gcc.22737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594006PMC
August 2019

Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

Lancet Diabetes Endocrinol 2019 03 16;7(3):213-220. Epub 2019 Jan 16.

Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Background: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection.

Methods: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features.

Findings: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs.

Interpretation: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.

Funding: None.
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http://dx.doi.org/10.1016/S2213-8587(18)30336-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132299PMC
March 2019

Concentrations of Selected Adipokines, Interleukin-6, and Vitamin D in Patients with Papillary Thyroid Carcinoma in Respect to Thyroid Cancer Stages.

Int J Endocrinol 2018 3;2018:4921803. Epub 2018 Dec 3.

Department of Pathophysiology and Endocrinology, School of Medicine with the Division of Dentistry, Medical University of Silesia, Zabrze, Poland.

The relationships between thyroid cancer and obesity are not fully understood. Adipokines, proinflammatory cytokines, and vitamin D may mediate these associations. In this study, we estimated serum concentrations of leptin, adiponectin, chemerin, interleukin-6 (IL-6), and vitamin D in patients with papillary thyroid cancer (PTC). We searched for associations between the adipokines, IL-6, vitamin D, anthropometric parameters, and TNM AJCC/UICC 2017 classification in 177 patients diagnosed with PTC (151 women and 26 men). Normal weight patients were predominantly classified as clinical stage I. The prevalence of stages higher than I was significantly higher in PTC patients with BMI ≥ 25 or with metabolic syndrome. Using logistic regression waist circumference ≥ 88 cm in women and ≥102 cm in men, upper tertiles of IL-6 and leptin were associated with a higher clinical stage. There were no differences in the prevalence of microcarcinomas in analyzed groups (BMI ≥ 25 versus BMI < 25 and with metabolic syndrome presence versus without metabolic syndrome). No significant relationships between serum concentrations of leptin, adiponectin, chemerin, IL-6, vitamin D, and tumor size in PTC were found. Although insulin resistance represented by the HOMA index was associated with anthropometric variables and with serum leptin, adiponectin, chemerin, and IL-6 concentrations, in our study, no statistically significant relations with PTC staging were identified.
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http://dx.doi.org/10.1155/2018/4921803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304902PMC
December 2018

Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer.

Endocr Relat Cancer 2019 02;26(2):241-250

Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Vandetanib is an oral tyrosine kinase inhibitor approved for treatment of advanced symptomatic or progressive medullary thyroid cancer (MTC). The current study (Nbib1496313) evaluated the benefit-risk of two starting doses of vandetanib in patients with symptomatic or progressive MTC. Patients were randomized 1:1 to receive vandetanib 150 or 300 mg daily and followed for a maximum of 14 months (Part A), with the option to then enter an open-label phase (Part B) investigating vandetanib 100, 150, 200 and 300 mg daily doses. Efficacy was assessed in Part A, and safety and tolerability during Parts A and B up to 2 years post randomization. Eighty-one patients were randomized in Part A and 61 patients entered Part B, of whom 37 (60.7%) received 2 years of treatment. Overall, 25% of patients experienced an objective response (OR) at 14 months (OR rate, 0.29 (95% CI, 0.176-0.445) for 300 mg, and 0.20 (95% CI, 0.105-0.348) for 150 mg; one-sided P value approximately 0.43). The most common adverse events (AEs) included diarrhea, hypocalcemia, asthenia, QTc prolongation, hypokalemia and keratopathy, all at generally higher incidence with 300 vs 150 mg (Part A). Part B safety and tolerability was consistent with Part A. OR was observed with both vandetanib doses; the 300 mg dose showed a more favorable trend vs 150 mg as initial dose. Thus, for most patients, 300 mg vandetanib is the most appropriate starting dose; dose reductions to manage AEs and lower initial doses for patients with particular comorbidities can be considered.
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http://dx.doi.org/10.1530/ERC-18-0258DOI Listing
February 2019

Coexistence of Promoter Mutations and the V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients.

Int J Mol Sci 2018 Sep 6;19(9). Epub 2018 Sep 6.

Department of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

promoter (p) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of p mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the V600E mutation. A total of 189 consecutive PTC specimens with known mutational status were evaluated. p mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional p alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the p hotspot mutations were highly correlated with the presence of the V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of p mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.
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http://dx.doi.org/10.3390/ijms19092647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163174PMC
September 2018

131-I MIBG therapy of malignant pheochromocytoma and paraganglioma tumours - a single-centre study.

Endokrynol Pol 2018 12;69(3):246-251. Epub 2018 Apr 12.

Department of Nuclear Medicine and Endocrine Oncology,, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeża Armii Krajowej 15, 44-101 Gliwice, Poland.

Introduction: Pheochromocytomas and paragangliomas are rare tumors deriving from chromaffin cells of adrenal medulla or paraganglia. They are usually benign but 10-35% of them present malignant behavior. The aim of the study was to evaluate the efficacy and safety of 131-I MIBG therapy in malignant pheochromocytoma /paraganglioma patients (MPPGL).

Material And Methods: 18 patients (7 women and 11 men) were included in this study. Between 2002 and 2016 they underwent 131-I MIBG therapy because of MPPGL and their medical data were analyzed retrospectively. Clinical indications for the treatment included progressive disease or massive tissue involvement independently from disease progression. Tumor response for the first time was assessed 3 months after the last treatment according to Response Evaluation Criteria in Solid Tumors criteria and by 131-I MIBG scans.

Results: The mean single dose used was 7.25 GBq (196 mCi) and mean cumulative dose 33.08 GBq ( 894 mCi). In 2 (11%) patients complete tumor response was achieved. In 1 (6%) patient partial response was obtained. In 13 (72%) patients stable disease was observed. In 2 (11%) patients progression was diagnosed three months after treatment discontinuation. In the whole studied group the progression free survival time was 85 months and overall 5-year survival was 87%.

Conclusions: Radionuclide treatment with use of 131-I MIBG may be effective form of palliative treatment for patients with inoperative neoplasm spread, progressive disease or patients requiring alleviation of symptoms. < p > < /p >.
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http://dx.doi.org/10.5603/EP.a2018.0024DOI Listing
October 2018

Guidelines of Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma. 2018 Update.

Endokrynol Pol 2018 ;69(1):34-74

Nuclear Medicine and Endocrine Oncology Department; M.Sklodowska-Curie Memorial Institute - Cancer Center, Gliwice Branch, Wybrzeze AK 15, 44-100 Gliwice, Poland; Zakład Medycyny Nuklearnej i Endokrynologii Onkologicznej, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Wybrzeże AK 15, 44-100 Gliwice, Poland.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisła in November 2015 [1].
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http://dx.doi.org/10.5603/EP.2018.0014DOI Listing
July 2018

Heterogeneity of Thyroid Cancer.

Pathobiology 2018 6;85(1-2):117-129. Epub 2018 Feb 6.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.

There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.
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http://dx.doi.org/10.1159/000486422DOI Listing
October 2018

Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide.

Contemp Oncol (Pozn) 2017 30;21(2):115-122. Epub 2017 Jun 30.

Department of Endocrinology and Isotope Therapy, Military Institute of Medicine, Warsaw, Poland.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a large and very diverse group of neoplasms. Clinical presentation of NETs depends on the site of the primary tumor and whether the tumor is functioning (i.e., secreting peptides or neuroamines that produce symptoms). The diagnosis of GEP-NET is further complicated by symptomatic differences that occur depending on the type of secreted peptide or neuroamine. Due to their heterogeneity and unique characteristics, early diagnosis of GEP-NETs is difficult, which increases the likelihood of metastatic disease and reduces the scope of therapeutic possibilities. Thus, a multidisciplinary approach for the treatment of GEP-NETs is necessary. This review is the result of presentations that were delivered during an expert meeting on the treatment of GEP-NETs supported by Ipsen. We summarize the current knowledge on the epidemiology, incidence, diagnosis, and treatment of GEP-NETs. We examined the role of the somatostatin analog (SSA) lanreotide and the impact of the data from the recently published, randomized, double-blind, placebo-controlled CLARINET study (Controlled study of Lanreotide Antiproliferative Response In Neuroendocrine Tumors) on disease management. We also review the recent treatment options and recommendations for GEP-NETs.
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http://dx.doi.org/10.5114/wo.2017.68619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611500PMC
June 2017

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

Int J Mol Sci 2017 Aug 22;18(8). Epub 2017 Aug 22.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Institute-Cancer Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options.
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http://dx.doi.org/10.3390/ijms18081817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578203PMC
August 2017

Dynamic risk stratification in the follow-up of thyroid cancer: what is still to be discovered in 2017?

Endocr Relat Cancer 2017 11 18;24(11):R387-R402. Epub 2017 Aug 18.

Nuclear Medicine and Endocrine Oncology DepartmentM. Sklodowska-Curie Memorial Institute - Cancer Center, Gliwice, Poland

The adequate risk stratification in thyroid carcinoma is crucial to avoid on one hand the overtreatment of low-risk and on the other hand the undertreatment of high-risk patients. The question how to properly assess the risk of relapse has been discussed during recent years and resulted in a substantial change in our approach to risk stratification in differentiated thyroid cancer, proposed by the newest ATA guidelines. First initial risk stratification, based on histopathological data is carried out just after primary surgery. It should be emphasized, that a high quality of histopathological report is crucial for proper risk stratification. Next, during the follow-up, patients are restratified considering their response to treatment applied and classified to one of the following categories: excellent response, biochemical incomplete response, structural incomplete or indeterminate response. This new approach is called dynamic risk stratification as, in contrary to the previous rigid evaluation performed at diagnosis, reflects a real-time prognosis and thereby substantially influences and personalizes disease management. In this review, we raise some unresolved questions, among them the lack of prospective studies, fulfilling evidence-based criteria, necessary to validate this model of risk stratification. We also provided some data concerning the use of dynamic risk stratification in medullary thyroid cancer, not yet reflected in ATA guidelines. In conclusion, dynamic risk stratification allows for better prediction of the risk of recurrence in thyroid carcinoma, what has been demonstrated in numerous retrospective analyses. However, the validation of this approach in prospective studies seems to be our task for near future.
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http://dx.doi.org/10.1530/ERC-17-0270DOI Listing
November 2017

Age at diagnosis and gender modify the risk of 9q22 and 14q13 polymorphisms for papillary thyroid carcinoma.

Endokrynol Pol 2017 ;68(3):283-289

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland, Poland.

Introduction: Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interac-tion between SNPs and patient-related factors (age at diagnosis and gender).

Material And Methods: A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique.

Results: There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 × 10-7; rs1867277 OR = 1.59, p = 1 × 10-6; rs1443434 OR = 1.53, p = 1 × 10-5; rs944289 OR = 1.52, p = 4 × 10-5). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 × 10-4) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01).

Conclusions: the association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.
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http://dx.doi.org/10.5603/EP.2017.0021DOI Listing
December 2017

Advances in small molecule therapy for treating metastatic thyroid cancer.

Expert Opin Pharmacother 2017 Aug 3;18(11):1049-1060. Epub 2017 Jul 3.

a Nuclear Medicine and Endocrine Oncology Department , Maria Skłodowska-Curie Memorial Institute and Cancer Center , Gliwice Branch, Gliwice , Poland.

Introduction: Multi kinase inhibitors (MKIs) are new drugs, which show activity against receptors of different growth factors leading to the inhibition of tumor cells growth and proliferation. This review summarizes a 10-year experience with the use of MKIs in thyroid cancer (TC). It focuses not only on sorafenib, lenvatinib, vandetanib and cabozantinib, already approved in TC, but also presents an overview of the results of different trials with distinct MKIs so far carried out in TC. Areas covered: Published results of phase I, II and III studies and other reports evaluated the efficacy of different targeted drugs in TC. Expert opinion: Despite numerous clinical trials with distinct MKIs, only four of them unequivocally demonstrated a beneficial effect on progression free survival in radioiodine refractory differentiated or medullary TC. In contrast to other solid tumors, we are still lacking in convincing evidences of their impact on overall survival. We still do not have any strong proof fulfilling evidence-based medicine criteria, when to start MKIs and which drug to use. The questions whether we really have to wait for disease progression in patients with a large tumor burden and/or aggressive types TC or when to stop MKIs treatment remain open.
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http://dx.doi.org/10.1080/14656566.2017.1340939DOI Listing
August 2017

Gene Expression (mRNA) Markers for Differentiating between Malignant and Benign Follicular Thyroid Tumours.

Int J Mol Sci 2017 Jun 2;18(6). Epub 2017 Jun 2.

Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute-Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (, , , , , , and ). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (, , , ). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.
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http://dx.doi.org/10.3390/ijms18061184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486007PMC
June 2017
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