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Purpose Peptide receptor radionuclide therapy (PRRT) and somatostatin analogues (SSAs) are commonly combined as primary treatment for neuroendocrine neoplasm (NEN), and SSAs given as maintenance treatment. We sought to evaluate whether sequential therapy with PRRT followed by SSAs has progression or survival benefits in patients with NEN.Methods This prospective, randomised, single-centre study had as principal eligibility criteria: unresectable, locally-advanced, or metastatic, histologically-confirmed well-differentiated NEN; no symptoms of carcinoid syndrome; no SSAs or ≤3 months of SSAs before PRRT; and stable disease or partial/complete response after PRRT. Altogether 115 patients were randomised 2:1 to an SSA group (n=74) given octreotide acetate LAR every 4 weeks, or to a control group (n=41) receiving best supportive care. Octreotide treatment was to stop upon intolerable toxicity or patient refusal, or, at physician/patient discretion, upon progression. Primary study endpoint was progression-free survival (PFS).Results Overall, median (25th-75th percentile) follow-up from the first PRRT activity to death or latest observation was 6.6 (3.18-10.22) years. During that time, 71/115 patients (62%) progressed, 52/74 (70%) in the SSA group, 19/41 (46%) in the control group (p = 0.01). Eighty-eight /115 (76%) patients died, 58/74 (78%) in the SSA group, 30/41 (73%) in the control group (p = 0.52). Median (95% CI) PFS was respectively, 4.7 (2.8-7.7) in the SSA group, and 6.4 (4.1-not reached) years in controls. Median OS was 6,6 years in whole group of patients. Neither PFS nor OS differed between groups (p = 0.129, p = 0.985, respectively).Conclusions In patients with disease control after PRRT, subsequent SSA treatment appeared not to be associated with better PFS or OS. Whether to continue or stop SSA administration upon progression after PRRT requires evaluation in a prospective, randomised, controlled multicenter study with a relatively homogeneous sample.

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.

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].

Wstep: Zespol mnogich nowotworow gruczolow dokrewnych typu 2 (MEN 2) jest schorzeniem uwarunkowanym genetycznie, dziedziczonym w sposob autosomalny dominujący, spowodowanym mutacją germinalną protoonkogenu RET. W 80% przypadkow mutacje zlokalizowane są w kodonie 634. Guz chromochlonny rozwinie sie u 50% pacjentow z zidentyfikowaną mutacją w protoonkogenie RET. Material i metody: 228 nosicieli mutacji w protonkogenie RET poddano monitorowaniu w kierunku rozwoju guza chromochlonnego. Nadzor obejmowal okresowo wykonywane ocene stanu klinicznego, wydalania metoksykatecholamin w dobowej zbiorce moczu komplementarnie z diagnostyką obrazową (CT, MR, scyntygrafia MIBG). Wyniki: Guz chromochlonny rozwinąl sie u 41 pacjentow (18% wszystkich pacjentow z ustaloną mutacją w protoonkogenie RET). Średni wiek rozpoznania wynosil 43 lata. W 8 przypadkach guz chromochlonny byl pierwszą kliniczną manifestacją MEN 2. Tylko u 8 pacjentow (20%) w chwili rozpoznania obserwowano objawy kliniczne typowe dla guza chromochlonnego. Średnia wielkośc guza wynosila 4,3 cm. Nie stwierdzono poza nadnerczowej lokalizacji. W obserwacji autorow potwierdzono tylko jeden przypadek zlośliwego guza chromochlonnego. Wnioski: Guzy wywodzące sie z tkanki chromochlonnej rozwijające sie w przebiegu zespolu MEN 2 mają zwykle nadnerczową lokalizacje i lagodny charakter jednak z duzą czestością zmian obustronnych. Biorąc pod uwage powyzsze ryzyko, a takze niespecyficzny obraz kliniczny istotnym jest monitorowanie wszystkich pacjentow z potwierdzoną mutacją w protoonkogenie RET w kierunku rozwoju guza chromochlonnego. (Endokrynol Pol 2016; 67 (1): 54–58)

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].

Introduction: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy. Material and methods: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0. Results: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) — including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) — occurred in one patient after three lines and in one patient after two lines; anaemia (25%) — in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2–3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months. Conclusions: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied. (Endokrynol Pol 2014; 65 (6): 472–478)

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).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.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%.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.

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. (Endokrynol Pol 2014; 65 (1): 40–45)

AimAlthough 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 to131I therapy duringl-thyroxin withdrawal (THW).MethodsPatients with the diagnosis of DTC who were ≤18 years of age and had no signs of persistent disease at the time of131I 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,PResultsOn the day of131I 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 after131I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (P>0.05).ConclusionsIn 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.

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant genetic syndrome caused by germline mutation in RET proto-oncogene. The most common mutations are in a cysteine rich domain. Phaeochromocytoma will develop in approximately 50% of RET proto-oncogene carriers.The studied population consisted of 228 RET proto-oncogene mutation carriers. Monitoring for the diagnosis of phaeochromocytoma was carried out in all patients with established genetic status. Mean time of follow up was 138 months. Surveillance consisted of periodically performed clinical evaluation, 24-hour urinary determinations of total metanephrines complementary with imaging (CT, MR, MIBG scintigraphy).Phaeochromocytoma developed in 41 patients (18% of all RET proto-oncogene mutations carriers). The mean age of diagnosis for the whole cohort was 43 years. In eight cases phaeochromocytoma was the first manifestation of the MEN 2 syndrome. Only eight (20%) patients were symptomatic at diagnosis of phaeochromocytoma. The mean size of the tumour was 4.3 cm. There was no extra-adrenal localisation. We observed one case of malignant phaeochromocytoma.In patients with MEN 2 syndrome phaeochromocytomas are usually benign adrenal tumours with high risk of bilateral development. Taking to account the latter risk and non-specific clinical manifestation of the neoplasm it is mandatory to screen all RET proto-oncogene mutations carriers for phaeochromocytoma.

The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy.Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-6720%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0.Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) - including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) - occurred in one patient after three lines and in one patient after two lines; anaemia (25%) - in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2-3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months.Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied.

CONCLUSIONS Radiolabelled somatostatin analogues, administered in patients with functional pNET, allow for good control of clinical symptoms and objective tumor response. RESULTS Clinical symptoms, resulting from excessive hormonal production, decreased after the first course of radiopeptide therapy and completely resolved at the end of the treatment in all treated patients. Seven patients with functional pNET were treated with radiolabelled somatostatin analogues. Complete remission of hormonal activity ranged from 11 to 79 months (a median time of 36 months). Three subjects suffered from symptoms recurrence after a median time of 22 months from the ends of the therapy.

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.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.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.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.

Summary During the two years ofthe studies (1997–1998) 32802 flower buds ofthirty Polish onion genotypes were plated on different media. In total 310 embryos (0.9 %) were obtained, out of which more than a half underwent regeneration. It was established that 3.5–4.5 mm long flower buds were the most responsive to gynogenesis. Out of 6 studied media combinations the highest yield of gynogenic embryos was produced on the B5 or BDS media containing 2.0mg/L 2,4-0 and 2.0mg/L 6BA (denoted as Al and F6 induction media, respectively) followed by the R regeneration medium (BDS supplemented with 1.0 mg/L NAA and 2.0 mg/L 2iP). It was observed that the cultivars differed with regard to their demands for media composition. The yield of embryos strongly depended on the genotype. For 9 genotypes the induction of gynogenesis failed, 12 genotypes yielded 0.2–0.8 % embryos, eight produced 1.0–4.3% embryos while only one gave 10.0% embryos.

The F0-F1 ATPase subunit 9 gene of carrot mitochondria has been isolated from both petaloid male-sterile (atp9-1) and normal fertile cytoplasms (atp9-3). The position occupied in atp9-3 by the TAA stop codon is, in the case of atp9-1 replaced by the CAA triplet coding for glutamine, which makes this latter ORF 13 amino acid residues longer than that of the atp9-3. The 3’ end of atp9-3 gene is flanked by a direct repeat of 42 bp. The sequence of the repeat unit is also present at the 3’ end of atp9-1 but without reiteration. A truncated and presumably inactive version of atp9 (atp9-2) was found to be present in cytoplasms regardless of the fertility phenotype which they condition. The atp9-1 gene from petaloid cytoplasm appeared to be co-transcribed with the gene coding for 5S rRNA, and nuclear background influenced the accumulation of the respective transcript. The results are discussed with respect to a potential role of atp9-1 in generating the petaloid form of CMS.

Urinary iodine concentrations were analyzed in the morning urine samples of patients with differentiated thyroid cancer (DTC).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.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. Ioduria200 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).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.

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.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).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.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.

Three cases of pheochromocytoma in children/adolescents or young adults treated by 131I-MIBG are presented in this study. In one patient 131I-MIBG was administrated after ineffective surgical treatment and chemotherapy of a benign retroperitoneal tumor, whereas in two other patients 131I-MIBG therapy was carried out because of malignant pheochromocytoma dissemination. In a child with retroperitoneal paraganglioma decrease of tumor size and its fibrosis after 131I-MIBG therapy allowed radical surgery and complete recovery. In two other cases partial remission was achieved. All patients showed a good subjective response with improvement of the general condition and better blood pressure control. In two children adverse reactions such as leucopenia, hypothyroidism or hypogonadism were observed. The presented data confirm effectiveness and acceptable tolerance of 131I-MIBG treatment in pheochromocytoma, what is very important in pediatric patients.

We found that the Sw-5 gene confers resistance to one of the Polish isolates of tomato spotted wilt virus (TSWV). A series of tomato breeding accessions was analysed along with standards of resistance and susceptibility to TSWV. The presence of the Sw-5 gene was determined using the available PCR marker. Subsequently plants from these accessions were grown in the presence of the TSWV isolate from Poland. Some of them developed severe symptoms of the TSWV disease. Expression of the virus proteins was also assayed in tissues of the investigated plants. We found general agreement between either lack or presence of the disease symptoms, virus proteins and resistance gene. Some observed discrepancies of these data are also discussed. Our results indicate that marker-assisted selection can be used for breeding of the TSWV-resistant tomato in Poland.

A high level of the nucleotide sequence conservation was found for mitochondrial nad3 gene of carrot. Three silent nucleotide substitutions differentiate nad3 open reading frames from cytoplasmic male sterile and male fertile carrots. All these differences are preserved on the RNA level. Partial and silent editing also distinguished both carrots. Three of the C to U conversions were specific to the fertile line. In the two examined carrot lines editing did not affect the mode of alteration of encoded amino acids.

Four methods for screening carrot ( Daucus carota L.) germplasm for resis- tance to bacterial soft rot were compared. There were differences in resistance among strains, with most severe damage caused by Erwinia carotovora pv. carotovora SR 394 (L.R. Jones) Holland and Erwinia carotovora pv. atroseptica SR 159 (van Hall) Jen- nison. Inoculation of cross-section al root slices with bacteria applied in suspension- soaked paper disks produced the most consistent response. The severity of disease damage was proportional to bacterial suspension concentration. With the development of a standard screening method, it may be possible for breeders to breed carrots with reduced susceptibility to soft rot. Erwinia carotovora is the causal agent of soft rot of carrot. This disease causes severe root losses of carrot, mainly during post- harvest storage, but also in the field late in the growing season. The soft-rot bacterium is especially destructive on carrot at high temperature and high humidity (Segall and Dow, 1973). The soft-rot Erwinia spp. occur worldwide and are usually present in soil and water. They may also be disseminated by insects (Phillips and Kelman, 1982). Be- cause most soft-rot Erwinia spp. attack many crops and are not host-specific, it is not un- common to isolate more than one species or

The frequency of Graves’ orbitopathy (GO) in patients with Graves’ disease (GD) depends on the method of assessment. Diagnosis based on clinical symptoms is made in about 30-50% patients, more often (70%) after ophtalmological examination with evaluation of intraocular pressure, whereas MRI reveals GO in up to 90%. Proper identification of active phase of the disease is crucial.

TKI constitute a new group of drugs evaluated in TC patients. The efficacy of some of them in prolongation of progression free survival has been recently documented. However, possible side effects may affect the quality of life as well as limit their clinical use. Only drugs which were known to inhibit VEGFR were considered. In the study adverse effects were evaluated in patients treated in our centre within the prospective clinical trials phase II and III. The aim of the study was to analyze the frequency and severity of side effects related to TKI in TC patients. Thus, we retrospectively re-evaluated side effects on the basis of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The comparison of the drugs was not aimed. 37 therapies with TKI due to advanced TC were assessed. 19 subjects were given vandetanib, 15 - lenvatinib, 3 - axitinib. Median treatment duration was 26.7 months (range: 4.0 - 62.2). The drug was discontinued due to TC progression in 9 subjects, adverse events in 5 and for other reasons in 4. Adverse events leading to treatment withdrawal were: weight loss (1), lymphopenia (1), QTC prolongation (1), tracheo-esophageal fistula (1) and purulent meningitis (1). The results are given in table ​table11. Table 1 Frequency and severity of the most common treatment-related side effects.