Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Jarosław Bogdan Ćwikła
Based on 12 articles published since 2009
(Why 12 articles?)
||||

Between 2009 and 2019, J. Cwikla wrote the following 12 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). 2017

Kos-Kudła, Beata / Blicharz-Dorniak, Jolanta / Strzelczyk, Janusz / Bałdys-Waligórska, Agata / Bednarczuk, Tomasz / Bolanowski, Marek / Boratyn-Nowicka, Agnieszka / Borowska, Małgorzata / Cichocki, Andrzej / Ćwikła, Jarosław B / Falconi, Massimo / Foltyn, Wanda / Handkiewicz-Junak, Daria / Hubalewska-Dydejczyk, Alicja / Jarząb, Barbara / Junik, Roman / Kajdaniuk, Dariusz / Kamiński, Grzegorz / Kolasińska-Ćwikła, Agnieszka / Kowalska, Aldona / Król, Robert / Królicki, Leszek / Krzakowski, Maciej / Kunikowska, Jolanta / Kuśnierz, Katarzyna / Lampe, Paweł / Lange, Dariusz / Lewczuk-Myślicka, Anna / Lewiński, Andrzej / Lipiński, Michał / Londzin-Olesik, Magdalena / Marek, Bogdan / Nasierowska-Guttmejer, Anna / Nawrocki, Sergiusz / Nowakowska-Duława, Ewa / Pilch-Kowalczyk, Joanna / Rosiek, Violetta / Ruchała, Marek / Siemińska, Lucyna / Sowa-Staszczak, Anna / Starzyńska, Teresa / Steinhof-Radwańska, Katarzyna / Sworczak, Krzysztof / Syrenicz, Anhelli / Szawłowski, Andrzej / Szczepkowski, Marek / Wachuła, Ewa / Zajęcki, Wojciech / Zemczak, Anna / Zgliczyński, Wojciech / Zieniewicz, Krzysztof. ·Klinika Endokrynologii i Nowotworów Neuroendokrynnych, Katedra Patofizjologii i Endokrynologii, Śląski Uniwersytet Medyczny. endoklin@sum.edu.pl. ·Endokrynol Pol · Pubmed #28597909.

ABSTRACT: 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.

2 Guideline Pancreatic neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours). 2017

Kos-Kudła, Beata / Rosiek, Violetta / Borowska, Małgorzata / Bałdys-Waligórska, Agata / Bednarczuk, Tomasz / Blicharz-Dorniak, Jolanta / Bolanowski, Marek / Boratyn-Nowicka, Agnieszka / Cichocki, Andrzej / Ćwikła, Jarosław B / Falconi, Massimo / Foltyn, Wanda / Handkiewicz-Junak, Foltyn / Hubalewska-Dydejczyk, Alicja / Jarząb, Barbara / Jarząb, Michał / Junik, Roman / Kajdaniuk, Dariusz / Kamiński, Grzegorz / Kolasińska-Ćwikła, Agnieszka / Kowalska, Aldona / Król, Robert / Królicki, Leszek / Kunikowska, Jolanta / Kuśnierz, Katarzyna / Lampe, Paweł / Lange, Dariusz / Lewczuk-Myślicka, Anna / Lewiński, Andrzej / Lipiński, Michał / Londzin-Olesik, Magdalena / Marek, Bogdan / Nasierowska-Guttmejer, Anna / Nowakowska-Duława, Ewa / Pilch-Kowalczyk, Joanna / Ruchała, Marek / Siemińska, Lucyna / Sowa-Staszczak, Anna / Starzyńska, Teresa / Steinhof-Radwańska, Katarzyna / Strzelczyk, Janusz / Sworczak, Krzysztof / Syrenicz, Anhelli / Szawłowski, Andrzej / Szczepkowski, Marek / Wachuła, Ewa / Zajęcki, Wojciech / Zemczak, Anna / Zgliczyński, Wojciech. ·vml@wp.pl. ·Endokrynol Pol · Pubmed #28540973.

ABSTRACT: This article presents updated diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine tumours (PNEN), proposed by the Polish Network of Neuroendocrine Tumours. The guidelines contain new data received in the years 2013-2016, which confirm previous recommendations, and have led to modification of previous guidelines or have resulted in the formulation of new guidelines. Biochemical and imaging (anatomical and functional) tests are of great importance in diagnostics, as well as histopathological diagnosis to determine the management of PNEN patients, but they must be confirmed by an immunohistochemical examination. PNEN therapy requires collaboration among the members a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment in many cases. Further therapy requires a multidirectional procedure; therefore, the rules of biotherapy, peptide receptor radionuclide therapy, molecular targeted therapy, and chemotherapy are discussed.

3 Guideline Gastroduodenal neuroendocrine neoplasms, including gastrinoma - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours). 2017

Lipiński, Michał / Rydzewska, Grażyna / Foltyn, Wanda / Andrysiak-Mamos, Elżbieta / Bałdys-Waligórska, Agata / Bednarczuk, Tomasz / Blicharz-Dorniak, Jolanta / Bolanowski, Marek / Boratyn-Nowicka, Agnieszka / Borowska, Małgorzata / Cichocki, Andrzej / Ćwikła, Jarosław B / Falconi, Massimo / Handkiewicz-Junak, Daria / Hubalewska-Dydejczyk, Alicja / Jarząb, Barbara / Junik, Roman / Kajdaniuk, Dariusz / Kamiński, Grzegorz / Kolasińska-Ćwikła, Agnieszka / Kowalska, Aldona / Król, Robert / Królicki, Leszek / Kunikowska, Jolanta / Kuśnierz, Katarzyna / Lampe, Paweł / Lange, Dariusz / Lewczuk-Myślicka, Anna / Lewiński, Andrzej / Londzin-Olesik, Magdalena / Marek, Bogdan / Nasierowska-Guttmejer, Anna / Nowakowska-Duława, Ewa / Pilch-Kowalczyk, Joanna / Poczkaj, Karolina / Rosiek, Violetta / Ruchała, Marek / Siemińska, Lucyna / Sowa-Staszczak, Anna / Starzyńska, Teresa / Steinhof-Radwańska, Katarzyna / Strzelczyk, Janusz / Sworczak, Krzysztof / Syrenicz, Anhelli / Szawłowski, Andrzej / Szczepkowski, Marek / Wachuła, Ewa / Zajęcki, Wojciech / Zemczak, Anna / Zgliczyński, Wojciech / Kos-Kudła, Beata. ·grazka3558@yahoo.pl. ·Endokrynol Pol · Pubmed #28540972.

ABSTRACT: 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.

4 Guideline ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. 2016

Garcia-Carbonero, R / Sorbye, H / Baudin, E / Raymond, E / Wiedenmann, B / Niederle, B / Sedlackova, E / Toumpanakis, C / Anlauf, M / Cwikla, J B / Caplin, M / O'Toole, D / Perren, A / Anonymous6950853. ·Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain. ·Neuroendocrinology · Pubmed #26731334.

ABSTRACT: -- No abstract --

5 Review Peptide Receptor Radionuclide Therapy for Advanced Gastroenteropancreatic Neuroendocrine Tumors - from oncology perspective. 2018

Kolasińska-Ćwikła, Agnieszka / Łowczak, Anna / Maciejkiewicz, Katarzyna Maciejkiewicz / Ćwikła, Jarosław Bogdan. ·Maria Sklodowska-Curie Memorial Cancer Center and Institiute of Oncology, Wawelska 15, 02-034 Warszawa, Poland. adkolasinska@yahoo.com. ·Nucl Med Rev Cent East Eur · Pubmed #29741203.

ABSTRACT: Peptide Receptor Radionuclide Therapy (PRRT) is a form of molecular targeted therapy which is performed by using a small peptide (somatostatin analogue - SSA) that is coupled with a radionuclide beta emitting radiation. PRRT is a nuclear medicine for the systemic treatment of non-resectable, metastasized well/moderately differentiated, neuroendocrine tumours (NET) with overexpression of somatostatin receptor. These types of tumours include gastroenteropancreatic neoplasm (GEP-NENs), e.g. arising from the small bowel (often called carcinoid tumours), the pancreas, duodenum or stomach, but also from the large bowel or the lung and many other tissues (so called diffuse neuroendocrine system). The goal of PRRT is irradiation of tumour cells, via direct binding into specific receptor, somatostatin receptors (SSTR) family, overexpressed on the cell membrane of the primary tumours as well as on the metastasis. Over many years of clinical use of PRRT with ⁹⁰Y and current with ¹⁷⁷Lu DOTA conjugated somatostatin analogues proved to be efficient therapy option for NETs, with tumour responses, base on radiological evaluation. Also, a clinical response with symptoms relief and improvement in quality of life based on standard EORTC questioners is seen. Additional, common NET biomarker reduction and, ultimately, an impact on overall survival (OS) of patients with advanced non-resectable often progressive NEN can be expected. PRRT with ⁹⁰Y or ¹⁷⁷Lu-labelled peptides is generally well tolerated by most of the patients. The acute side effects (Adverse Events - AEs) are usually mild; most of them are related to the co-administration of amino acids (AA), such as nausea and vomiting. Others are related to the radioisotopes, such as fatigue or the exacerbation of endocrine syndromes, which are very rarely and they occurs, only in patients with functional tumours and large tumours burden. Chronic and permanent damage has an effect on target organs, particularly the kidneys and the bone marrow, which are generally mild. Currently, when ¹⁷⁷Lu DOTATATE is used, the potential risk to kidney damage is significantly reduced, compared to the previous usage of ⁹⁰Y labelled analogues. Up to now, kidney and bone marrow toxicity limits the dose of radioactivity of PRRT.

6 Clinical Trial Baseline chromogranin A and its dynamics are prognostic markers in gastroenteropancreatic neuroendocrine tumors. 2017

Rogowski, Wojciech / Wachuła, Ewa / Lewczuk, Anna / Kolasińska-Ćwikła, Agnieszka / Iżycka-Świeszewska, Ewa / Sulżyc-Bielicka, Violetta / Ćwikła, Jarosław B. ·Clinical Department of Chemotherapy, Hospital Ministry of the Interior & Administration & Warmia & Mazury Oncology Centre, Olsztyn, Poland. · Department of Medical Science, University of Varmia & Masuria, Olsztyn, Poland. · Department of Endocrinology, Medical University of Gdańsk, Gdańsk, Poland. · Department of Clinical Oncology, Maria-Skłodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland. · Department of Pathology & Neuropathology, Medical University of Gdańsk, Gdańsk, Poland. · Department of Oncology, Pomeranian Medical University, Szczecin, Poland. ·Future Oncol · Pubmed #28095720.

ABSTRACT: AIM: This study assessed whether absolute chromogranin A (CgA) values at various stages of treatment have prognostic value in patients with pancreatic and midgut neuroendocrine tumors, subjected to peptide receptor radionuclide therapy with PATIENTS & METHODS: CgA was determined before peptide receptor radionuclide therapy, 6 weeks, 6, 12, 18 and 24 months after the last dose of RESULTS: Elevated baseline CgA concentrations and their relative increase within the first year of observation were unfavorable predictors of overall survival, but not progression. CONCLUSION: Even a single baseline measurement of CgA can be useful in establishing prognosis in this group, if this parameter exceeds its upper normal limit more than tenfold.

7 Clinical Trial Long-term efficacy of (90)Y-DOTATATE in patients with nonresectable pancreatic and small bowel neuroendocrine neoplasms. 2016

Rogowski, Wojciech / Wachuła, Ewa / Lewczuk, Anna / Buscombe, John R / Seklecka, Nina / Sankowski, Artur / Ćwikła, Jarosław B. ·Clinical Department of Chemotherapy, Hospital Ministry of the Interior & Administration & Warmia & Mazury Oncology Centre, Olsztyn, Poland. · Department of Endocrinology, Medical University of Gdansk, Gdansk, Poland. · Department of Nuclear Medicine & PET, Addenbrooke's Hospital, Cambridge, UK. · Department of Radiology & Diagnostic Imaging, Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland. · Faculty of Medical Science, University of Varmia & Masuria, Olsztyn, Poland. ·Future Oncol · Pubmed #27156864.

ABSTRACT: AIM: To determine the efficacy of (90)Y [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) in 67 patients with pancreatic and small bowel neuroendocrine tumors (NETs). PATIENTS & METHODS: The primary efficacy end point was overall survival (OS) and secondary end points were progression-free survival (PFS) and tumor response. RESULTS: Median PFS in pancreatic and small bowel NETs was 25 and 28 months, respectively, and median OS was 42 and 38.5 months, respectively. No intergroup differences in median OS (p = 0.945) or PFS (p = 0.174) were found, also after adjustment for tumor origin, secretory status and grade, and patient's gender. CONCLUSION: (90)Y-DOTATATE may have similar efficacy in pancreatic and small bowel NETs. Better WHO performance status at baseline seems to be associated with more favorable outcomes.

8 Clinical Trial Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. 2016

Caplin, Martyn E / Pavel, Marianne / Ćwikła, Jarosław B / Phan, Alexandria T / Raderer, Markus / Sedláčková, Eva / Cadiot, Guillaume / Wolin, Edward M / Capdevila, Jaume / Wall, Lucy / Rindi, Guido / Langley, Alison / Martinez, Séverine / Gomez-Panzani, Edda / Ruszniewski, Philippe / Anonymous721030. ·Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France m.caplin@ucl.ac.uk. · Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France. · Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France Royal Free HospitalLondon, UKCharité University Medicine BerlinBerlin, GermanyUniversity of Warmia and MazuryOlsztyn, PolandUniversity of Texas MD Anderson Cancer CenterHouston, Texas, USAUniversity HospitalVienna, AustriaDepartment of Oncology of the First Faculty of Medicine and General Teaching HospitalPrague, Czech RepublicRobert-Debré HospitalReims, FranceMarkey Cancer CenterUniversity of Kentucky, Lexington, Kentucky, USAVall d'Hebron University HospitalBarcelona, SpainWestern General HospitalEdinburgh, UKUniversità Cattolica del Sacro CuoreRome, ItalyIpsenLes Ulis, FranceIpsenBasking Ridge, New Jersey, USABeaujon HospitalClichy, FranceParis Diderot UniversityParis, France. ·Endocr Relat Cancer · Pubmed #26743120.

ABSTRACT: In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1/2 (Ki-67 ≤ 10%) non-functioning NET and documented baseline tumour-progression status received lanreotide Autogel 120 mg (n = 101) or placebo (n = 103) for 96 weeks or until death/progressive disease (PD) in CLARINET study. Patients with stable disease (SD) at core study end (lanreotide/placebo) or PD (placebo only) continued or switched to lanreotide in the OLE. In total, 88 patients (previously: lanreotide, n = 41; placebo, n = 47) participated: 38% had pancreatic, 39% midgut and 23% other/unknown primary tumours. Patients continuing lanreotide reported fewer adverse events (AEs) (all and treatment-related) during OLE than core study. Placebo-to-lanreotide switch patients reported similar AE rates in OLE and core studies, except more diarrhoea was considered treatment-related in OLE (overall diarrhoea unchanged). Median lanreotide PFS (core study randomisation to PD in core/OLE; n=101) was 32.8 months (95% CI: 30.9, 68.0). A sensitivity analysis, addressing potential selection bias by assuming that patients with SD on lanreotide in the core study and not entering the OLE (n=13) had PD 24 weeks after last core assessment, found median PFS remaining consistent: 30.8 months (95% CI: 30.0, 31.3). Median time to further PD after placebo-to-lanreotide switch (n=32) was 14.0 months (10.1; not reached). This OLE study suggests long-term treatment with lanreotide Autogel 120 mg maintained favourable safety/tolerability. CLARINET OLE data also provide new evidence of lanreotide anti-tumour benefits in indolent and progressive pancreatic/intestinal NETs.

9 Clinical Trial Lanreotide in metastatic enteropancreatic neuroendocrine tumors. 2014

Caplin, Martyn E / Pavel, Marianne / Ćwikła, Jarosław B / Phan, Alexandria T / Raderer, Markus / Sedláčková, Eva / Cadiot, Guillaume / Wolin, Edward M / Capdevila, Jaume / Wall, Lucy / Rindi, Guido / Langley, Alison / Martinez, Séverine / Blumberg, Joëlle / Ruszniewski, Philippe / Anonymous1220800. ·From Royal Free Hospital, London (M.E.C.) · Charité University Medicine Berlin, Berlin (M.P.) · University of Warmia and Mazury, Olsztyn, Poland (J.B.Ć.) · University of Texas M.D. Anderson Cancer Center, Houston (A.T.P.) · University Hospital, Vienna (M.R.) · Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic (E.S.) · Robert-Debré Hospital, Reims (G.C.), Ipsen, Les Ulis, (A.L., S.M., J.B.), Beaujon Hospital, Clichy (P.R.), and Paris Diderot University, Paris (P.R.) - all in France · Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles (E.M.W.) · Vall d'Hebron University Hospital, Barcelona (J.C.) · Western General Hospital, Edinburgh (L.W.) · and Università Cattolica del Sacro Cuore, Rome (G.R.). ·N Engl J Med · Pubmed #25014687.

ABSTRACT: BACKGROUND: Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. METHODS: We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. RESULTS: Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). CONCLUSIONS: Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

10 Clinical Trial Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. 2010

Cwikla, J B / Sankowski, A / Seklecka, N / Buscombe, J R / Nasierowska-Guttmejer, A / Jeziorski, K G / Mikolajczak, R / Pawlak, D / Stepien, K / Walecki, J. ·Department of Radiology and Diagnostic Imaging, Medical Centre for Postgraduate Education and Central Clinical Hospital of Ministry of Internal Affairs and Administration, 137 Woloska, Warsaw, Poland. jaroslaw.cwikla@cskmswia.pl ·Ann Oncol · Pubmed #19833821.

ABSTRACT: BACKGROUND: To evaluate the clinical and radiological effectiveness of [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) Y-90 in patients with extensive progressive gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs). MATERIALS AND METHODS: Sixty patients with histologically proven GEP-NETs were treated with DOTATATE Y-90. Clinical responses were assessed 6 weeks after completing therapy and then after each of the 3- to 6-month intervals. The radiological response was classified according to RECIST criteria. RESULTS: At 6 months after final treatment, radiological partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was observed in 13 patients (23%), and the remaining patients had stable disease (SD; less than 30% decrease in the sum of the longest diameter of target lesions or less than 20% increase in the sum of the longest diameter of target lesions) (77%). Clinical PR at 6 months was in 43 patients (72%), nine patients had SD and progressive disease (PD) was noted in eight patients. Median progression-free survival (PFS) was 17 months, while the median overall survival (OS) was 22 months. In eight patients with early PD, the PFS was 4.5 and OS 9.5 months, while in those with SD or PR, PFS and OS were 19.5 and 23.5 months, respectively. After 12 months of follow-up, five patients had World Health Organization (WHO) grade 2 or 3 renal toxicity. Haematological toxicity (WHO grade 3 and 4) was noted during therapy in 10% of patients and persisted in 5%. CONCLUSIONS: DOTATATE Y-90 therapy is effective and relatively safe in patients with GEP-NET. Standard doses of DOTATATE Y-90 result in a relatively low risk of myelotoxicity. However, due to ongoing risk of renal toxicity, careful monitoring of the kidney is recommended.

11 Article Glutaminases in slowly proliferating gastroenteropancreatic neuroendocrine neoplasms/tumors (GEP-NETs): Selective overexpression of mRNA coding for the KGA isoform. 2016

Szeliga, Monika / Ćwikła, Jarosław / Obara-Michlewska, Marta / Cichocki, Andrzej / Albrecht, Jan. ·Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. Electronic address: mszeliga@imdik.pan.pl. · Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, 30 Warszawska Str., 10-082 Olsztyn, Poland. · Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland. · Department of Surgical Oncology, Maria Skłodowska-Curie Memorial Cancer Center, Institute of Oncology, 15B Wawelska Str., 02-034 Warsaw, Poland. ·Exp Mol Pathol · Pubmed #26581715.

ABSTRACT: Glutamine (Gln) is a crucial metabolite in cancer cells of different origin, and the expression and activity of different isoforms of the Gln-degrading enzyme, glutaminase (GA), have variable implications for tumor growth and metabolism. Human glutaminases are encoded by two genes: the GLS gene encodes the kidney-type glutaminases, KGA and GAC, while the GLS2 gene encodes the liver-type glutaminases, GAB and LGA. Recent studies suggest that the GAC isoform and thus high GAC/KGA ratio, are characteristic of highly proliferating tumors, while GLS2 proteins have an inhibitory effect on tumor growth. Here we analyzed the expression levels of distinct GA transcripts in 7 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with low proliferation index and 7 non-neoplastic tissues. GEP-NETs overexpressed KGA, while GAC, which was the most abundant isoform, was not different from control. The expression of the GLS2 gene showed tendency towards elevation in GEP-NETs compared to control. Collectively, the expression pattern of GA isoforms conforms to the low proliferative capacity of GEP-NETs encompassed in this study.

12 Article 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. 2014

Wachuła, Ewa / Ćwikła, Jarosław B / Rogowski, Wojciech / Boratyn-Nowicka, Agnieszka / Szabłowska-Siwik, Sylwia / Piątek, Michał / Zemczak, Anna / Michalik, Barbara / Jarząb, Barbara / Nawrocki, Sergiusz / Kos-Kudła, Beata. ·Division of Radiotherapy and Oncology, Department of Clinical Oncology, Silesian Medical University, Katowice, Poland. e.wachula@wp.pl. ·Endokrynol Pol · Pubmed #25554616.

ABSTRACT: 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.