Conventionally fractionated radiotherapy versus CyberKnife hypofractionated radiotherapy for painful vertebral haemangiomas - A randomized clinical trial.

BACKGROUND AND PURPOSE: The outcomes of conventional radiotherapy for painful vertebral haemangiomas have been improved through dose escalation at the expense of overall treatment time. We hypothesized that with the aid of precise hypofractionated radiotherapy, it is possible to safely deliver a similar biological equivalent dose over a significantly shorter course of treatment with a comparable efficacy and safety. MATERIALS AND METHODS: In this prospective, single-institution unblinded randomized clinical trial (NCT02332408) patients with painful vertebral haemangiomas were allocated one-to-one either to 25 Gy delivered in five fractions (CK) or conventionally fractionated radiotherapy up to 36 Gy (conv.). The main endpoint was pain relief at two years, measured on a subjective and numerical scale (NRS). RESULTS: The trial was finished yielding 74 evaluable patients, including 38 in the CK arm. Adverse events were infrequent and the treatment was well tolerated. The overall treatment time was significantly shorter in the CK arm (median of 13 days vs 25 days). At two years, more than half of the patients reported improvement (46; 62.2 %) , in 21 cases the pain symptoms were stable (28.4 %), and in seven cases worse (9.5 %). There were significantly more patients reporting improvement in the CK arm (73.7 % vs 50 %; p = 0.036). The median decrease in NRS was 4 (IQR 1-5) or 59 % (IQR 20-86 %), and the difference between arms was not statistically significant. CONCLUSION: Five fractions hypofractionated radiotherapy for painful vertebral haemangiomas up to a total dose of 25 Gy is a safe treatment modality, significantly shorter compared to conventional fractionation, and possibly more effective.

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.

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

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 Wisla in November 2015 [1].

18-Fluorodeoxy-Glucose Positron Emission Tomography- Computed Tomography (18-FDG-PET/CT) for Gross Tumor Volume (GTV) Delineation in Gastric Cancer Radiotherapy

Purpose: Evaluation of the 18-fluorodeoxy-glucose positron emission tomography-computed tomography (18-FDGPET/ CT) for gross tumor volume (GTV) delineation in gastric cancer patients undergoing radiotherapy. Methods: In this study, 29 gastric cancer patients (17 unresectable and 7 inoperable) were initially enrolled for radical chemoradiotherapy (45Gy/25 fractions + chemotherapy based on 5 fluorouracil) or radiotherapy alone (45Gy/25 fractions) with planning based on the 18-FDG-PET/CT images. Five patients were excluded due to excess blood glucose levels (1), false-negative positron emission tomography (1) and distant metastases revealed by 18-FDG-PET/CT (3). The analysis involved measurement of metabolic tumor volumes (MTVs) performed on PET/CT workstations. Different threshold levels of the standardized uptake value (SUV) and liver uptake were set to obtain MTVs. Secondly, GTVPET values were derived manually using the positron emission tomography (PET) dataset blinded to the computed tomography (CT) data. Subsequently, GTVCT values were delineated using a radiotherapy planning system based on the CT scans blinded to the PET data. The referenced GTVCT values were correlated with the GTVPET and were compared with a conformality index (CI). Results: The mean CI was 0.52 (range, 0.12-0.85). In 13/24 patients (54%), the GTVPET was larger than GTVCT, and in the remainder, GTVPET was smaller. Moreover, the cranio-caudal diameter of GTVPET in 16 cases (64%) was larger than that of GTVCT, smaller in 7 cases (29%), and unchanged in one case. Manual PET delineation (GTVPET) achieved the best correlation with GTVCT (Pearson correlation = 0.76, p <0.0001). Among the analyzed MTVs, a statistically significant correlation with GTVCT was revealed for MTV10%SUVmax (r = 0.63; p = 0.0014), MTVliv (r = 0.60; p = 0.0021), MTVSUV2.5 (r = 0.54; p = 0.0063); MTV20%SUVmax (r = 0.44; p = 0.0344); MTV30%SUVmax (r = 0.44; p = 0.0373). Conclusion: 18-FDG-PET/CT in gastric cancer radiotherapy planning may affect the GTV delineation.

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

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.

Analysis of selected allergic reactions among psoriatic patients.

INTRODUCTION: Psoriasis is a chronic and recurrent inflammatory skin disease. The aetiology is still unknown in spite of numerous scientific researches. There is very little evidence which does not provide enough knowledge about allergic reactions in psoriatic patients. Based on the fact that the epidermal barrier damage allows different allergen types to penetrate into deep layers of epidermis and skin, we can assume that it may lead to immunological reactions. AIM: To investigate the allergic reaction indicators and hypersensitivity assessment about contact, inhalant and food allergens. The results were analysed with regard to clinical disease indicators and progression stage of dermal lesions. MATERIAL AND METHODS: Eighty patients with psoriasis were examined. The concentration of total IgE antibodies and allergen specific IgE antibodies (asIgE) were analysed. Standard epidermal tests and atopy patch tests were performed. All the patients were estimated for their dermatological condition based on the PASI scale. The control group consisted of 50 patients without psoriasis and allergic history. RESULTS: Significantly higher concentration of total E immunoglobulin has been stated in the patients with psoriasis. Higher concentrations of specific allergic IgE antibodies were more often observed in the examined group but the most frequently observed values were present in 1-3 class. The most common airborne allergens were birch, artemisia, timothy and rye pollens. There have not been any significant statistical differences in the case of positive epidermal test results. CONCLUSIONS: There is slightly expressed hypersensitivity in psoriatic patients. This hypersensitivity degree correlates with the intensification of symptoms.

Diagnostics and Treatment of Thyroid Carcinoma.

Revised Guidelines of Polish National Societies Prepared on the initiative of the Polish Group for Endocrine Tumours approved in their final version between November 16th and 28th, 2015 by the Scientific Committee of the V Conference "Thyroid Cancer and other malignancies of endocrine glands" organised between November 14th and 17th, 2015 in Wisla, Poland; called by the following Societies: Polish Endocrine Society, Polish Society of Oncology, Polish Thyroid Association, Polish Society of Pathologists, Society of Polish Surgeons, Polish Society of Surgical Oncology, Polish Society of Clinical Oncology, Polish Society of Radiation Oncology, Polish Society of Nuclear Medicine, Polish Society of Paediatric Endocrinology, Polish Society of Paediatric Surgeons, Polish Society of Ultrasonography Gliwice-Wisla, 2015 DECLARATION: These recommendations are created by the group of delegates of the National Societies, which declare their willingness to participate in the preparation of the revised version of the Polish Guidelines. The members of the Working Group have been chosen from the specialists involved in medical care of patients with thyroid carcinoma. Directly before the preparation of the Polish national recommendations the American Thyroid Association (ATA) published its own guidelines together with a wide comment fulfilling evidence-based medicine (EBM) criteria. ATA Guidelines are consistent with National Comprehensive Cancer Network (NCCN) Recommendation. According to the members of the Working Group, it is necessary to adapt them to both the specific Polish epidemiological situation as well as to the rules referring to the Polish health system. Therefore, the Polish recommendations constitute a consensus of the experts' group, based on ATA information. The experts analysed previous Polish Guidelines, published in 2010, and other available data, and after discussion summed up the results in the form of these guidelines. It should be added that Part II, which constitutes a pathological part, has been available at the website of the Polish Society of Pathologists for acceptance of the members of the Society, and no essential comments have been proposed. The Members of the Group decided that a subgroup elected from among them would update the Guidelines, according to EBM rules, every year. The Revised Guidelines should help physicians to make reasonable choices in their daily practice; however, the final decision concerning an individual patient should be made by the caring physician responsible for treatment, or optimally by a therapeutic tumour board together with the patient, and should take into consideration the patient's health condition. It should be emphasised that the recommendations may not constitute a strict standard of clinical management imposed on medical staff. The data from clinical trials concerning numerous clinical situations are scarce. In such moments the opinion of the management may differ from the recommendations after considering possible benefits and disadvantages for the patient.

Novel genetic variants in differentiated thyroid cancer and assessment of the cumulative risk.

A genome-wide association study (GWAS) performed on a high-incidence Italian population followed by replications on low-incidence cohorts suggested a strong association of differentiated thyroid cancer (DTC) with single nucleotide polymorphisms (SNPs) at 9q22.33, 2q35, 20q11.22-q12 and 14q24.3. Moreover, six additional susceptibility loci were associated with the disease only among Italians. The present study had two aims, first to identify loci involved in DTC risk and then to assess the cumulative effect of the SNPs identified so far in the Italian population. The combined analysis of the previous GWAS and the present Italian study provided evidence of association with rs7935113 (GALNTL4, OR = 1.36, 95%CI 1.20-1.53, p-value = 7.41 × 10(-7)) and rs1203952 (FOXA2, OR = 1.29, 95%CI 1.16-1.44, p-value = 4.42 × 10(-6)). Experimental ENCODE and eQTL data suggested that both SNPs may influence the closest genes expression through a differential recruitment of transcription factors. The assessment of the cumulative risk of eleven SNPs showed that DTC risk increases with an increasing number of risk alleles (p-trend = 3.13 × 10(-47)). Nonetheless, only a small fraction (about 4% on the disease liability scale) of DTC is explained by these SNPs. These data are consistent with a polygenic model of DTC predisposition and highlight the importance of association studies in the discovery of the disease hereditability.

Novel genome-wide association study-based candidate loci for differentiated thyroid cancer risk.

CONTEXT: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3). Our recently published GWAS suggested additional susceptibility loci specific for the high-incidence Italian population. OBJECTIVE: The purpose of this study was to identify novel Italian-specific DTC risk variants based on our GWAS and to test them further in low-incidence populations. DESIGN: We investigated 45 SNPs selected from our GWAS first in an Italian population. SNPs that showed suggestive evidence of association were investigated in the Polish and Spanish cohorts. RESULTS: The combined analysis of the GWAS and the Italian replication study (2260 case patients and 2218 control subjects) provided strong evidence of association with rs10136427 near BATF (odds ratio [OR] =1.40, P = 4.35 × 10(-7)) and rs7267944 near DHX35 (OR = 1.39, P = 2.13 × 10(-8)). A possible role in DTC susceptibility in the Italian populations was also found for rs13184587 (ARSB) (P = 8.54 × 10(-6)) and rs1220597 (SPATA13) (P = 3.25 × 10(-6)). Only the associations between rs10136427 and rs7267944 and DTC risk were replicated in the Polish and the Spanish populations with little evidence of population heterogeneity (GWAS and all replications combined, OR = 1.30, P = 9.30 × 10(-7) and OR = 1.32, P = 1.34 × 10(-8), respectively). In silico analyses provided new insights into the possible functional consequences of the SNPs that showed the strongest association with DTC. CONCLUSIONS: Our findings provide evidence for novel DTC susceptibility variants. Further studies are warranted to identify the specific genetic variants responsible for the observed associations and to functionally validate our in silico predictions.

Radioactive iodine (RAI) treatment of hyperthyroidism is safe in patients with Graves' orbitopathy--a prospective study.

INTRODUCTION: Radioactive iodine (RAI) therapy may induce or worsen orbitopathy (GO) in Graves' disease (GD). The aim of this study was a prospective assessment of the risk of GO exacerbation in a GD patients cohort submitted to RAI therapy for hyperthyroidism. MATERIAL AND METHODS: 208 consecutive GD patients treated with 131I in 2007 were enrolled. The analysis was performed on 156 patients strictly monitored for one year. Glucocorticosteroid (GCS) prophylaxis was administered if GO symptoms or GO history were present, and in cases of tobacco smokers even without GO symptoms. Clinical and biochemical evaluation at one, three, six, and 12 months after therapy was performed in the whole group, then at 24 months in 138 patients. RESULTS: There was no severe GO progression in patients without GO symptoms at the time of RAI treatment. The risk of severe GO worsening for preexisting GO patients (demanding systemic GCS administration) during the 12-month follow-up after RAI therapy was 10%. 12 and 24 months after 131I administration, stable improvement compared to the initial GO status had been achieved in most (98-96%) patients. CONCLUSIONS: 1. In patients with mild GO, the risk of severe GO worsening after RAI therapy is acceptable, as long as RAI therapy is applied with GCS cover. 2. In patients without GO symptoms at the time of RAI therapy but with a history of GO and with subclinical GO diagnosed by MRI only, the risk of severe progression is minimal. 3. Distant outcomes of RAI treatment confirmed its safety in GO patients.

Genome-wide association study on differentiated thyroid cancer.

CONTEXT: Genome-wide association studies (GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1), and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered. OBJECTIVE: Our objective was to identify additional common DTC susceptibility loci. DESIGN: We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in 2 additional Italian series and in 3 low-incidence populations totaling 2958 cases and 3727 controls. RESULTS: After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952, confirming the recently published association in DIRC3 (odds ratio [OR] = 1.21, P = 6.4 × 10(-10), GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 × 10(-6); and OR = 1.25, P = 5.7 × 10(-6)), rs7617304 in RARRES1 (OR = 1.25, P = 4.6 × 10(-5)) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 × 10(-5)). CONCLUSIONS: Our findings provide additional insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Additional studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice.

SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.

BACKGROUND: Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative. OBJECTIVES: The objective of this study was to identify susceptibility genes for PTC. METHODS: A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies. RESULTS: Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants. CONCLUSIONS: Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type.

Role of nuclear medicine imaging in differential diagnosis of accessory spleens in patients after splenectomy.

BACKGROUND: More than 10% of healthy population has one or more accessory spleens. The most common location is the hilum of the spleen or area near the tail of the pancreas. The radiological appearance of accessory spleens in oncologic patients who underwent splenectomy can be misinterpreted as a recurrence, especially in the case of compensatory growth of an accessory spleen in successive radiological examinations. CASER REPORTS: We present the cases of three patients who underwent splenectomy for gastric carcinoid, gastric adenocarcinoma and cancer of the left adrenal gland, respectively. CT examination and/or PET-CT scan revealed suspicious findings in the left upper abdomen. In one patient, the dimensional increase of this finding in successive examinations was initially considered suggestive for cancer recurrence. Scintigraphy with (99m)Tc-nanocolloid was able to confirm the presence of an accessory spleen in all these patients. CONCLUSIONS: Splenic scintigraphy is an economical, accessible and accurate tool in differential diagnosis of accessory spleens in patients after splenectomy.

Urinary iodine in patients with differentiated thyroid cancer (DTC) during L-thyroxine treatment.

INTRODUCTION: Urinary iodine concentrations were analyzed in the morning urine samples of patients with differentiated thyroid cancer (DTC). MATERIAL AND METHODS: The analyzed group included 572 DTC patients who were treated with radioiodine or hospitalized for evaluation of radioiodine treatment effects in 2009 at the Institute of Oncology in Gliwice. Ioduria was analyzed by PAMM (Program Against Micronutrient Malnutrition) method before rhTSH administration. A total of 545 tests were performed during L-thyroxine treatment and 27 after L-thyroxine withdrawal. RESULTS: Median L-thyroxine dose was 150 µg/day. Median ioduria was 127.5 µg/L during L-thyroxine therapy and 134 µg/L after the L-thyroxine withdrawal. No distinct relation between ioduria and L-thyroxine dose was observed. Ioduria < 200 µg/L was observed in over 90% of patients and this cut-off was chosen for the reference range. Only 1.2% of patients showed a distinct stable iodine contamination (ioduria ≥ 300 µg/L). CONCLUSIONS: Urinary iodine concentrations in differentiated thyroid cancer patients treated with L-thyroxine vary in a wide range and do not show a clear relation with L-thyroxine dose.

Genetic predisposition to papillary thyroid cancer.

Approximately 5% of differentiated thyroid cancers are hereditary. Hereditary non-medullary thyroid cancer may occur as a minor component of familial cancer syndromes (e.g. familial adenomatous polyposis) or as a primary feature (familial non-medullary thyroid cancer [FNMTC]). Among FNMTC, PTC is the most common. Although a hereditary predisposition to non-medullary thyroid cancer is well established, the susceptibility genes are poorly known. Up to now, by linkage analysis using microsatellite markers, several putative loci have been described - 1q21, 6q22, 8p23.1-p22, and 8q24; however, validation studies have been unsuccessful. In the present review we discuss the results of linkage analysis and the most recent results of genome wide association studies (GWAS) with high resolution SNP (single nucleotide polymorphism) arrays.

Has differentiated thyroid cancer (DTC) staging changed with in the last ten years in the Silesia region of Poland?

INTRODUCTION: The aim of the study was to compare the advancement of thyroid cancer at diagnosis in Polish patients from the Silesian district in the years 1999 and 2008. MATERIAL AND METHODS: The analyzed group consisted of Silesian district patients with thyroid cancer, who were registered by the Department of Tumour Epidemiology of the Institute of Oncology in Gliwice in the years 1999 and 2008. From a group of 186 patients who entered on record in 1999, 167 were qualified for this analysis. Similarly, from 238 patients registered in 2008, finally 226 were added. We analyzed: sex, age at diagnosis, histotype of thyroid cancer, and DTC staging according to TNM (UICC 2002). In 1999 there were 137 females (82.04 %) and 30 males (17.93%) with thyroid cancer diagnosed at ages 5-81 years. In 2008 there were 183 females (80.97%) and 43 males (19.03%) diagnosed at ages 14-80 years. In both groups, in 1999 and 2008, the median age was the same (51 years). RESULTS: In the year 1999, 119 (71%) and in 2008, 197 (87%) patients were diagnosed with papillary thyroid cancer (p = 0.0003). Relations between age and sex were similar in these years. There was some increase in frequency of patients diagnosed with papillary microcancer (pT1a), which was on the border of statistical significance (p = 0.05). A statistically significant increase of pT1 (p = 0.02) and decrease of pT4 (p = 0.001) and of pTx (p = 0.002) was observed in the year 2008 in the whole cohort of DTC patients. CONCLUSIONS: 1. In 2008 the contribution of papillary histotype to all thyroid cancer patients (87%) was significantly higher than in 1999. 2. The percentage of DTC patients diagnosed with pT1 disease was significantly higher in 2008.