Publications by authors named "Daria Handkiewicz-Junak"

51 Publications

Factors Modifying Outcome After MIBG Therapy in Children With Neuroblastoma-A National Retrospective Study.

Front Oncol 2021 12;11:647361. Epub 2021 Apr 12.

Department of Pediatric Oncology, Hematology and Transplantology (EBMT CIC 641, CIBMTR Center 10797), University of Medical Sciences, Poznań, Poland.

Background: Neuroblastoma is the most common pediatric extracranial tumor with varied prognoses, but the survival of treated refractory or relapsing patients remains poor.

Objective: This analysis presents the outcomes of children with neuroblastoma undergoing MIBG therapy in Poland in 2006-2019.

Study Design: A retrospective cohort of 55 patients with refractory or relapsed neuroblastoma treated with I-131 MIBG in Poland in 2006-2019 was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of second cancers and CI of hypothyroidism. Survival curves were estimated using the Kaplan-Meier method and compared between the cohorts by the log-rank test. Cox modeling was adopted to estimate hazard ratios for OS and EFS, considering factors with P < 0.2.

Results: Fifty-five patients with a median age of 78.4 months (range 18-193) with neuroblastoma underwent one or more (4 patients) courses of MIBG I-131 therapy. Fifteen patients were not administered chemotherapy, 3 children received standard-dose chemotherapy, and 37 patients were administered high-dose chemotherapy (HDCT) (busulfan-melphalan in 24 and treosulfan-based in 12 patients). Forty-six patients underwent stem cell transplantation, with autologous (35 patients), haploidentical (6), allogeneic (4), and syngeneic grafts (1). The median time from first MIBG therapy to SCT was 22 days. Children with relapsing tumors had inferior OS compared to those with primary resistant disease (21.2% vs 58.7%, p=0.0045). Survival was better in patients without MYCN gene amplification. MIBG therapy was never curative, except in patients further treated with HDCT with stem cell rescue irrespective of the donor type. 31 patients were referred for immune therapy after MIBG therapy, and the 5-year OS in this group was superior to the untreated children (55.2% vs 32.7%, p=0.003), but the difference in the 5-year EFS was not significant (25.6% vs 32.9%, p=ns). In 3 patients, a second malignancy was diagnosed. In 19.6% of treated children, hypothyroidism was diagnosed within 5 years after MIBG therapy.

Conclusion: MIBG therapy can be incorporated into the therapeutic strategy of relapsed or resistant neuroblastoma patients as preconditioning with HDCT rather than stand-alone therapy. Follow-up is required due to the incidence of thyroid failure and risk of second cancers.
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http://dx.doi.org/10.3389/fonc.2021.647361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075349PMC
April 2021

Laparoscopic cortical-sparing adrenal surgery in pheochromocytomas associated with hereditary neoplasia syndromes.

Endokrynol Pol 2020 30;71(6):518-523. Epub 2020 Oct 30.

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

Introduction: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas.

Material And Methods: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3-1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5-4 years).

Results: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved.

Conclusions: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.
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http://dx.doi.org/10.5603/EP.a2020.0075DOI Listing
October 2020

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
October 2020

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

Follow-up of low risk thyroid cancer patients: can we stop follow-up after 5 years of complete remission?

Eur J Endocrinol 2020 May;182(5):D1-D16

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

Each year, the proportion of thyroid cancer patients presenting with low-risk disease is increasing. The shift in the landscape of thyroid cancer presentation is forcing clinicians to re-evaluate not only management but also surveillance paradigms. During the follow-up, patients are stratified considering their response to treatment and classified into one of the following response categories: excellent, biochemical incomplete, structural incomplete, or indeterminate. These categories reflect a real-time prognosis and thereby substantially influence and personalise disease management. Although at present, no guideline recommends stopping differentiated thyroid carcinoma (DTC) surveillance at any particular time point, the relatively low prevalence of treatment failures in low-risk patients may prompt early discontinuation of surveillance in this subgroup. Therefore, this debate will present an overview of the controversies surrounding the surveillance of low-risk patients with DTC.
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http://dx.doi.org/10.1530/EJE-19-0960DOI Listing
May 2020

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

Surgical approach to differentiated thyroid cancers (DTC) in children [Specyfika leczenia chirurgicznego zróżnicowanych raków tarczycy (ZRT) u dzieci].

Endokrynol Pol 2019 ;70(4):357-366

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

Thyroid cancer in children is rare and accounts for 1-3% of all malignant tumours. Differentiated thyroid cancers (DTC) and particularly papillary thyroid carcinoma (PTC) (90% of cases) are the most prevalent. Surgery is the mainstay of treatment in patients with DTC. The current recommendations are based not on prospective randomised clinical trials, but on retrospective trials and expert opinions. Therefore, it is not easy to choose the optimal therapeutic strategy to obtain the best treatment and to avoid serious complications and adverse events. In children and adolescents, the clinical presentation, course, and prognosis are different from those seen in adults. Children are generally at low risk of death but at higher risk of long-term harm due to overly aggressive treatment. Therefore, optimisation of the therapeutic strategy is particularly important. The present paper provides a summary of the current guidelines on surgical management in thyroid tumours and DTC in children and adolescents.
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http://dx.doi.org/10.5603/EP.a2019.0033DOI Listing
February 2020

European Perspective on 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: Proceedings of an Interactive International Symposium.

Thyroid 2019 01 7;29(1):7-26. Epub 2019 Jan 7.

18 Department of Endocrinology and Metabolism, Endocrine Tumor Center at WTZ, Essen University Hospital, Essen, Germany.

Background: The American Thyroid Association (ATA) management guidelines for patients with thyroid nodules and differentiated thyroid cancer (DTC) are highly influential practice recommendations. The latest revision appeared in 2015 ("ATA 2015"). These guidelines were developed predominantly by North American experts. European experts frequently have different perspectives, given epidemiological, technological/methodological, practice organization, and medicolegal differences between the respective regions.

Summary: Divergent viewpoints were the focus of an invited symposium organized by the European Association of Nuclear Medicine involving 17 European thyroidologists, four ATA Guidelines Taskforce members, and an audience of 200 international experts. The group discussed the preoperative assessment of thyroid nodules, surgery and the role of pathology, radioiodine (RAI) therapy (RAIT), the assessment of initial therapy and dynamic risk stratification, and the treatment of persistent disease, recurrences, and advanced thyroid cancer. The dialogue resulted in this position paper contrasting European and ATA 2015 perspectives on key issues. One difference pertains to the permissiveness of ATA 2015 regarding lobectomy for primary tumors ≤4 cm. European panelists cited preclusion of RAIT, potential need for completion thyroidectomy, frequent inability to avoid chronic thyroid hormone replacement, and limitations of supportive evidence as arguments against widely applying lobectomy. Significant divergence involved ATA 2015's guidance regarding RAIT. European panelists favored wider use of postoperative RAIT than does ATA 2015. Rationales included the modality's association with favorable patient outcomes and generally limited toxicity, and lack of high-quality evidence supporting withholding RAIT. Additionally, European panelists favored recombinant human thyrotropin (rhTSH) in more settings than does ATA 2015, citing avoidance of hypothyroid morbidity and quality-of-life impairment, without apparent sacrifice in oncologic outcomes. Based on clinical evidence plus theoretical advantages, European experts advocated dosimetric versus fixed-activity RAIT approaches for advanced DTC. European panelists noted that the ATA 2015 risk-stratification system requires information sometimes unavailable in everyday practice. ATA 2015 recommendations regarding RAI-refractory DTC should consider potential palliative benefits of RAIT in patients who also have RAI-susceptible lesions.

Conclusions: European panelists suggested modifications to approximately one-third of ATA 2015 recommendations. Varying European and ATA 2015 perspectives can stimulate analysis and discussion of the literature and performance of primary research to resolve discrepant recommendations and potentially improve patient outcomes.
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http://dx.doi.org/10.1089/thy.2017.0129DOI Listing
January 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

EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides.

Eur J Nucl Med Mol Imaging 2018 05 16;45(5):846-859. Epub 2018 Feb 16.

Institute of Nuclear Medicine and Endocrinology, Kepler University Hospital, Linz, Austria.

The skeleton is the most common metastatic site in patients with advanced cancer. Pain is a major healthcare problem in patients with bone metastases. Bone-seeking radionuclides that selectively accumulate in the bone are used to treat cancer-induced bone pain and to prolong survival in selected groups of cancer patients. The goals of these guidelines are to assist nuclear medicine practitioners in: (a) evaluating patients who might be candidates for radionuclide treatment of bone metastases using beta-emitting radionuclides such as strontium-89 (Sr), samarium-153 (Sm) lexidronam (Sm-EDTMP), and phosphorus-32 (P) sodium phosphate; (b) performing the treatments; and
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http://dx.doi.org/10.1007/s00259-018-3947-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978928PMC
May 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

EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer.

Eur J Nucl Med Mol Imaging 2018 05 12;45(5):824-845. Epub 2017 Dec 12.

Institute of Nuclear Medicine and Endocrinology, Kepler University Hospital, Krankenhausstrasse 9, 4020, Linz, Austria.

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.
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http://dx.doi.org/10.1007/s00259-017-3900-4DOI Listing
May 2018

Survey on Paediatric Differentiated Thyroid Cancer Care in Europe.

Horm Res Paediatr 2018 17;89(1):58-62. Epub 2017 Nov 17.

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

Background/aims: Thyroid cancer among children is a very rare disease. Although survival is favourable, morbidity caused by the treatment remains considerable, so there is a great need to optimize management by international cooperation. For this reason, the 2016 European Thyroid Association-Cancer Research Network (ETA-CRN) meeting in Copenhagen, Denmark, paid considerable attention to this topic and aimed to give an overview of the care for this paediatric patient group in different European countries.

Methods: An inventory of data on thyroid cancer treatment among children in Europe was generated by questionnaires focused on treatment and organization of care.

Results: The treatment of paediatric thyroid cancer appears to be scattered in each European country with limited centralization of care, and different European countries use different treatment and follow-up protocols.

Conclusion: Collaboration in a European network to optimize treatment and minimize long-term consequences for paediatric thyroid cancer survivors is necessary. During this meeting, the ETA-CRN has endorsed the initiative to collaborate on this rare endocrine cancer within a European network.
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http://dx.doi.org/10.1159/000484170DOI Listing
October 2018

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

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2017 ;68(2):79-110

Klinika Endokrynologii i Nowotworów Neuroendokrynnych, Katedra Patofizjologii i Endokrynologii, Śląski Uniwersytet Medyczny.

Progress in the diagnostics and therapy of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN), the published results of new randomised clinical trials, and the new guidelines issued by the European Neuroendocrine Tumour Society (ENETS) have led the Polish Network of Neuroendocrine Tumours to update the 2013 guidelines regarding management of these neoplasms. We present the general recommendations for the management of NENs, developed by experts during the Third Round Table Conference - Diagnostics and therapy of gastro-entero-pancreatic neuroendocrine neoplasms: Polish recommendations in view of current European recommenda-tions, which took place in December 2016 in Żelechów near Warsaw. Drawing from the extensive experience of centres dealing with this type of neoplasms, we hope that we have managed to develop the optimal management system, applying the most recent achievements in the field of medicine, for these patients, and that it can be implemented effectively in Poland. These management guidelines have been arranged in the following order: gastric and duodenal NENs (including gastrinoma); pancreatic NENs; NENs of the small intestine and appendix, and colorectal NENs.
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http://dx.doi.org/10.5603/EP.2017.0015DOI Listing
July 2017

Colorectal neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2017 ;68(2):250-260

Neuroendocrine neoplasms/tumours (NENs/NETs) of the large intestine are detected increasingly often, especially rectal tumours, which is probably associated with the widespread use of screening colonoscopy. There is a growing body of evidence supporting the thesis that the NENs of the rectum and the NENs of the colon are two different diseases. Rectal NENs are usually small lesions, of low to moderate histological malignancy, associated with good prognosis, and most may be treated endoscopically. NENs of the colon, however, are often aggressive, poorly differentiated, associated with a poor or uncer-tain prognosis, and require surgical treatment. The management guidelines regarding these groups of patients are constantly changing. On the basis of the recent literature data and conclusions reached by the working meeting of the Polish Network of Neuroendocrine Tumours (December 2016), this study completes and updates the data and management guidelines regarding colorectal NENs published in Endokrynologia Polska 2013; 64: 358-368.
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http://dx.doi.org/10.5603/EP.2017.0019DOI Listing
July 2017

Neuroendocrine neoplasms of the small intestine and appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2017 ;68(2):223-236

This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered.
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http://dx.doi.org/10.5603/EP.2017.0018DOI Listing
July 2017

Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2017 ;68(2):138-153

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis, and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological, and localisation diagnoses. The principles of treatment are discussed, including endoscopic, surgical, pharmacological, and radionuclide treatments. Finally, there are also recommendations on patient monitoring.
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http://dx.doi.org/10.5603/EP.2017.0016DOI Listing
July 2017

Diagnostics and Treatment of Thyroid Carcinoma.

Endokrynol Pol 2016 ;67(1):74-107

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

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-Wisła, 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.
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http://dx.doi.org/10.5603/EP.2016.0011DOI Listing
February 2017

Ongoing risk stratification for differentiated thyroid cancer (DTC) - stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients.

Endokrynol Pol 2016 ;67(1):2-11

Nuclear Medine and Endocrine Oncology Department; M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch.

Introduction: Adequate postoperative risk assessment currently constitutes the principle of DTC treatment and further management. The aim of the study - a retrospective assessment of risk factors influencing DTC relapse.

Material And Methods: The study group consisted of 510 DTC staged pT1b-T4N0-N1M0, in whom total thyroidectomy and complementary radioiodine (RAI) treatment were carried out. In 71% papillary thyroid cancer was diagnosed, whereas in the remaining 29% - follicular thyroid carcinoma. Based on TNM classification from 1997, T1 feature was diagnosed in 11.6%, T2 in 35.1%, T3 in 8.4%, T4 in 9,4%, while in 35.5% - Tx. Lymph node metastases were present in 24.7% of cases. Median follow-up was 12.1 years (1.5-15.2).

Results: Age at DTC diagnosis, tumour diameter (T), lymph node metastases (N1), stimulated thyroglobulin, and RAI uptake in thyroid bed at qualification for RAI ablation significantly influenced freedom from progression time (FFP) in a multivariate analysis. When postoperative stimulated Tg was > 30 ng/mL the risk of relapse increased nearly six-fold, whereas the presence of N1 feature - four-fold. The total risk of relapse in the whole group was 12.55% while median FFP was 154.8 months. Five-year and 10-year FFP was 90.1% and 87.5%, respectively.

Conclusions: Postoperative stimulated thyroglobulin level was the most potent, independent risk factor influencing FFP in DTC patients. Age above 60 years, an initial DTC stage (T and N features), and low RAI uptake in thyroid bed ( < 1%) were related to a higher risk of DTC relapse, whereas the investigated histopathological features were insignificant.
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http://dx.doi.org/10.5603/EP.2016.0001DOI Listing
February 2017

Gene signature of the post-Chernobyl papillary thyroid cancer.

Eur J Nucl Med Mol Imaging 2016 Jul 26;43(7):1267-77. Epub 2016 Jan 26.

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

Purpose: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC.

Methods: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized.

Results: There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples.

Conclusion: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.
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http://dx.doi.org/10.1007/s00259-015-3303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869750PMC
July 2016

Recombinant human thyrotropin preparation for adjuvant radioiodine treatment in children and adolescents with differentiated thyroid cancer.

Eur J Endocrinol 2015 Dec 30;173(6):873-81. Epub 2015 Sep 30.

Department of Nuclear Medicine and Endocrine OncologyMaria Sklodowska-Curie Memorial Institute and Centre of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 14, 44-100 Gliwice, Poland.

Aim: Although recombinant human thyrotropin (rhTSH) is widely used in treating differentiated thyroid cancer (DTC), almost all clinical investigation has been in adults. The aim of our retrospective study was to evaluate outcomes of adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and to compare them to (131)I therapy during l-thyroxin withdrawal (THW).

Methods: Patients with the diagnosis of DTC who were ≤18 years of age and had no signs of persistent disease at the time of (131)I treatment were included; 48 patients were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of follow-up after therapy was 67 months and was longer in the THW group (99 vs 43 months, P<0.05).

Results: On the day of (131)I administration, all but one patient had TSH levels above 25 μIU/ml. Peak TSH concentration was significantly higher in the rhTSH group (152 μIU/ml vs 91 μIU/ml). Similarly, the thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8 ng/ml). No side effects requiring medical intervention were recorded after rhTSH administration. The evaluation of disease outcomes during TSH stimulation (6-18 months after (131)I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (P>0.05).

Conclusions: In children/adolescents, rhTSH-aided adjuvant radioiodine treatment is associated with rates of remnant ablation and short-term recurrence similar to THW. As this preparation has several advantages over THW, rhTSH may become the preferred method of TSH stimulation once studies of long-term outcomes show non-inferiority to THW in this age group.
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http://dx.doi.org/10.1530/EJE-15-0562DOI Listing
December 2015

The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors.

PLoS One 2015 15;10(7):e0132821. Epub 2015 Jul 15.

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

Introduction: The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients.

Material: 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases.

Results: BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours <= 10 mm were over-represented among BRAF negative population (p=0.03). No association between BRAF mutation and other clinicopathological factors was observed. BRAF status was associated neither with relapse nor with disease-free survival (DFS) (p=0.76). Nodal status, extrathyroidal invasion and tumour size significantly influenced DFS.

Conclusion: The risk of PTC recurrence is mainly related to the presence of lymph node metastases and extrathyroidal invasion, whereas no impact of BRAF V600E mutation has been demonstrated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132821PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503446PMC
May 2016

Sorafenib for the treatment of thyroid cancer: an updated review.

Expert Opin Pharmacother 2015 Mar 21;16(4):573-83. Epub 2015 Jan 21.

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Nuclear Medicine and Endocrine Oncology Department, Gliwice Branch , Gliwice , Poland + 48 32 2789301 ; +48 32 2789310 ;

Introduction: Sorafenib (Nexavar) is an oral multi-kinase inhibitor targeting B-type Raf kinase (BRAF) (both wild type and BRAF(V600E)), VEGFR1, VEGFR2, VEGFR3, PDGFRβ and RET (also RET/PTC) influencing both differentiated thyroid cancer (DTC) cell proliferation and angiogenesis.

Areas Covered: Encouraging results achieved in numerous Phase II trials were confirmed in a Phase III study conducted in radioiodine-refractory DTC. Sorafenib compared to placebo significantly prolongs progression-free survival, 10.8 versus 5.8 months, respectively. However, its administration resulted mainly in disease stabilization. No complete remission was obtained in any study. Beneficial effects were also demonstrated for medullary and anaplastic thyroid cancer; however further studies fulfilling evidence based medicine criteria are necessary. Its toxicity profile is convergent with other VEGFR inhibitors. The most common treatment-related side-effects involve skin toxicity (predominantly hand-foot skin reaction, different rashes and alopecia), gastrointestinal disturbances (diarrhea, abdominal pain), constitutional adverse reactions (anorexia, weight loss, fatigue) and hypertension. Although most adverse reactions are manageable, > 50% of patients required dose reduction.

Expert Opinion: Sorafenib constitutes the first line treatment option in advanced, radioiodine-refractory DTC. However, there are still no data on its efficacy in patients progressed after another tyrosine kinase inhibitor. Other applications of the drug, such as use as adjuvant therapy to 131-I treatment, requires further studies.
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http://dx.doi.org/10.1517/14656566.2015.1005601DOI Listing
March 2015

Neuroendocrine neoplasms of the small intestine and the appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2013 ;64(6):480-93

Division of Endocrinology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland.

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.
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http://dx.doi.org/10.5603/EP.2013.0029DOI Listing
September 2015

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours).

Endokrynol Pol 2013 ;64(6):418-43

Division of Endocrinology, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland.

An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.
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http://dx.doi.org/10.5603/EP.2013.0028DOI Listing
September 2015

Polish experience in Peptide receptor radionuclide therapy.

Recent Results Cancer Res 2013 ;194:467-78

Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.

Patients And Methods: During the period from April 2004 to December 2010, 358 patients underwent peptide receptor radionuclide therapy (PRRT) ((90)Y-DOTATATE, (177)Lu-DOTATATE, and (90)Y/(177)Lu-DOTATATE) in Poland.

Results: The majority of patients underwent (90)Y-DOTATATE therapy (n = 177) with progression-free survival (PFS)/time to progression (TTP) of 17-44 months and overall survival (OS) of 22-34.2 months. Twelve-month follow-up revealed stable disease (SD) in 46-60%, disease regression (RD) in 16-35%, disease progression (PD) in 7-17%, and complete remission (CR) in 3% of patients. In patients treated with (90)Y/(177)Lu-DOTATATE (n = 44), PFS/TTP was 24.2-28.3 months and OS was 49.8-52.8 months. Twelve-month follow-up showed SD in 62-70%, RD in 15-20%, and PD in 10-12% of patients. The treatment was well tolerated. No severe adverse events occurred. Grade 3 toxicity [in leucocytes (WBC) and thrombocytes (PLT)] was seen in 6-20% of patients treated with (90)Y-DOTATATE. In that group, renal toxicity grade 3 was seen in 5-12% and grade 4 in 3-8%. In patients treated with tandem therapy with (90)Y/(177)Lu-DOTATATE or (177)Lu-DOTATATE alone, hematological and renal toxicity grade 3 or 4 was not observed.

Conclusions: The results indicate that PRRT with the procedures and isotopes used is an effective and safe therapy option for patients with metastatic or inoperable neuroendocrine tumors (NETs). Our results suggest that tandem therapy with (90)Y/(177)Lu-DOTATATE provides longer overall survival than single-isotope treatment. Hematological toxicity was rare in all treated patients. Renal toxicity grade 3 and 4 was observed only in the group treated with (90)Y-DOTATATE.
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http://dx.doi.org/10.1007/978-3-642-27994-2_26DOI Listing
June 2013