Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Only peak thyroglobulin concentration on day 1 and 3 of rhTSH-aided RAI adjuvant treatment has prognostic implications in differentiated thyroid cancer.

OBJECTIVE: In patients with differentiated thyroid carcinoma (DTC), serum thyroglobulin levels measured at the time of remnant ablation after thyroid hormone withdrawal were shown to have prognostic value for disease-free status. We sought to evaluate serial thyroglobulin measurements at the time of recombinant human thyroid-stimulating hormone (rhTSH)-aided iodine 131 (131I) adjuvant treatment as prognostic markers of DTC. METHODS: Six hundred-fifty patients with DTC given total/near-total thyroidectomy and adjuvant radioiodine post-rhTSH stimulation were evaluated. Thyroglobulin was measured on day 1 (Tg1; at the time of the first rhTSH injection), day 3 (Tg3; 1 day after the second, final rhTSH injection), and day 6 (Tg6; 3 days post-radioiodine administration). Treatment failure was defined as histopathologically confirmed locoregional recurrence, or radiologically-evident distant metastases (signs of disease on computer tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci of radioiodine or [18F] fluorodeoxyglucose ([18F]FDG) uptake. RESULTS: In univariate analysis, Tg1 (p < 0.001) and Tg3 (p < 0.001), but not Tg6, were significantly associated with structural recurrence. In multivariate analysis of the overall cohort, only Tg3 was independently associated with structural recurrence. In multivariate analysis of the subgroup (n = 561) with anti-Tg antibodies titers below the institutional cut-off, 115 IU/mL, Tg1 was an independent prognostic marker. Tg1 and Tg3 cutoffs to best predict structural recurrence were established at 0.7 ng/mL and 1.4 ng/mL, respectively. CONCLUSIONS: Tg1 and Tg3, measurements made after rhTSH stimulation but before radioiodine treatment, independently predict a low risk of treatment failure in patients with DTC. Levels measured post-radioiodine application (e.g., Tg6) are highly variable, lack prognostic value, and hence can be omitted.

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

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.

Shared and unique metabolic features of the malignant and benign thyroid lesions determined with use of 1H HR MAS NMR spectroscopy.

The purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). 1H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol-in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.

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

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: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 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.

Fluorescence spectroscopy as tool for bone development monitoring in newborn rats.

Autofluorescence of the mandible and femur bones taken from newborn rats (7-, 14- and 28-day old) was studied. Endogenous fluorophores were excited with 231 nm, 291 nm, 340 nm and 360 nm wavelengths. Modifications in content and microenvironment of both noncolagenous and collagenous constituents of bone tissue as well as metabolic coenzymes during the bone formation with age were reflected in fluorescence emission spectra. The increase of emission from peptide bonds and tryptophan residues was noted with rat age while for collagen and metabolic coenzymes at the first 2 weeks only. After maternal administration of indinavir the changes in fluorescence intensity and shifts in position of peak maximum were found. The distinct drop of emission from peptide bonds and tryptophan residues in studied bones was detected. In the case of collagen and metabolic coenzymes the red shift of peak maximum was revealed. Fluorescence spectroscopy could be used to follow bone development in newborn rats and effect of maternal indinavir administration on offspring.