Anna Zemczak

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

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.

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

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.

Pancreatic neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine neoplasms (PNENs) proposed by the Polish Network of Neuroendocrine Tumours.These guidelines refer to biochemical (determination of specific and nonspecific neuroendocrine markers) and imaging diagnostics (EUS, CT, MR, and radioisotope examination with a 68Ga or 99Tc labelled somatostatin analogue).A histopathological diagnostic, which determines the further management of patients with PNENs, must be necessarily confirmed by immunohistochemical tests. PNENs therapy requires collaboration between a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment. Medical therapy requires a multidirectional procedure, and therefore the rules of biotherapy, peptide receptor radionuclide therapy, chemotherapy and molecular targeted therapy are discussed.

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

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 diagnosis. The principles of treatment are discussed, including endoscopic, surgical, pharmacological and radionuclide treatment. Finally, recommendations on patient monitoring are given.

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

Neuroendocrine neoplasms of the large intestine account for 20% of all neuroendocrine neoplasms (NENs) and are most commonly found in the rectum. The rate of detection of colorectal NENs is increasing, and this tendency will continue due to the widespread use of colonoscopy as a screening tool and the removal of all diagnosed lesions. This paper provides updated guidelines for the management of patients with colorectal NENs. Recent data on epidemiology, clinical characteristics, biochemical, and pathomorphological diagnosis as well as useful imaging techniques are presented. We look in detail at novel methods of treatment including endoscopic and surgical management, pharmacological and radioisotope therapy. We summarise monitoring of the treatment.

Zalecenia ogólne dotyczące postępowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

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.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients – results from the prospective 12-month phase of Lanro-Study

Aim of the study To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. Material and methods A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. Results 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage – 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care – 49%, hospitalization – 23%, diagnostics/laboratory tests – 28%). Conclusions These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

How often do we see incidental 68Ga-DOTATATE thyroid uptake in PET/CT in patients with neuroendocrine tumours?

INTRODUCTION Thyroid diseases, which may occur as focal or diffuse changes in thyroid parenchyma, are most often observed in women. AIM Our aim was to assess the prevalence of incidental thyroid uptake of 68Ga-DOTATATE PET/CT in patients referred to the Nuclear Medicine Department for evaluation of neuroendocrine neoplasia (NEN). MATERIAL AND METHODS We retrospectively evaluated 1150 68Ga-DOTATATE PET/CT images. Clinical history, serum TSH and thyroid antibody (TAb) concentrations, ultrasonography, and cytological assessment of the material from fine-needle aspiration biopsy (FNA) of the thyroid lesion were investigated. RESULTS We found incidental abnormalities in 46/1150 (4.1%) patients (12 men, 34 women). 34/46 patients (8 men, 26 women) showed diffuse 68Ga-DOTATATE thyroid uptake, with mean SUVmax 4.6 ± 1.6. Based on laboratory tests and ultrasound, we found: 38% of patients with an active autoimmune thyroiditis, 27% with benign goitre, and 6% with multinodular goitre with autoimmune thyroiditis. The remaining 29% of patients did not show any pathology. In 12/47 patients (4 men, 8 women) focal uptake in the thyroid with SUVmax 7.3 ± 3.3 was found. During one-year follow-up, category II and category III lesions (according to Bethesda classification) were revealed in 9/12 (75%) patients and in one patient, respectively. Histopathological examination after surgery revealed papillary thyroid carcinoma in one patient and benign multinodular goitre in another patient. CONCLUSIONS Patients with focal 68Ga-DOTATATE uptake should undergo further examination (FNA) due to potential risk of malignancy. Diffuse 68Ga-DOTATATE uptake was predominantly associated with active autoimmune thyroiditis or benign goitre. The focal lesions and diffuse pathology diseases were frequently seen in women.

Assessment of the safety and efficiency of sunitinib malate in metastatic neuroendocrine tumours of the pancreas (NEN G1/G2) depending on the number and type of earlier therapeutic lines — initial report

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.

TeleNEN as a telemedicine model for neuroendocrine neoplasm management in case of Meckel’s diverticulum NET

A case of 25- years-old female with NET deriving from Meckels diverticulum is described. The patient had one year history of dermatological skin problems. Ultrasound examination of abdomen performed because of arterial hypertension, revealed multiple hepatic lesions, which was confirmed in contrast enhanced CT. The typical contrast enhanced metastatic lesions in CT and elevated levels of chromogranin A suggested NET of unknown origin. SRS with 99mTc-HYNICTOC was perform for primary tumor localization, and revealed liver and paraaortic lymph nodes metastases, but no sign of primary tumor location. As a next step for primary tumor localization 68Ga-DOTATATE PET/CT was done, which revealed focus of increased uptake in small intestine considered to be the primary tumor site. The imaging and clinical history of patient was discussed on ENETS Tumor Board. Due to location of primary tumor in the small intestine with no anatomical changes in CT, laparotomy guided with gamma probe after 68Ga-DOTATATE injection was performed. During surgery procedure, the primary tumor was hardly palpable in the tip of Meckels diverticulum, confirmed by gamma probe. After surgery, tandem peptide receptor radionuclide therapy (PRRT) was started. Patient received 4 doses of 90Y/177Lu-DOTATATE with total activity of 360 mCi (13.32 GBq). The three months follow up 68Ga-DOTATATE PET/CT had shown stable disease of patient. The presented case showed importance role of multidisciplinary team cooperation in patient management. Use of RGS is essential in cases like presented, when the tumor cannot be localized only by surgical palpation.