XXXIX. IMUNOANALYTICKÉ DNY

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1 Záštitu nad konferencí převzali: prof. MUDr. Tomáš Zima, DrSc., MBA rektor Univerzity Karlovy prof. MUDr. Štěpán Svačina, DrSc., MBA předseda České lékařské společnosti Jana Evangelisty Purkyně, z.s. MUDr. Václav Šimánek, Ph.D. ředitel Fakultní nemocnice Plzeň Prof. MUDr. Jindřich Fínek, Ph.D. děkan Lékařské fakulty v Plzni, Univerzity Karlovy XXXIX. IMUNOANALYTICKÉ DNY března 2018 Program a sborník abstrakt Euroverlag

2 Konferenci pořádají: Česká společnost nukleární medicíny JEP a Česká společnost klinické biochemie JEP ve spolupráci s Fakultní nemocnicí Plzeň a Lékařskou fakultou v Plzni Univerzity Karlovy. Agentura pověřená organizací konference BOOSTER EVENT s.r.o. Tereza Stopková Marie Karlíková, Petr Šusta, 2018 This edition Euroverlag,

3 OBSAH ÚVODNÍ SLOVO... 4 VĚDECKÝ A ORGANIZAČNÍ VÝBOR KONFERENCE... 5 ČASOVÝ ROZVRH... 6 ODBORNÝ PROGRAM... 7 VYZVANÍ ŘEČNÍCI...14 ABSTRAKTA...31 PLENÁRNÍ PŘEDNÁŠKY...32 BLOK 1: KARCINOM PROSTATY Z RŮZNÝCH ÚHLŮ POHLEDU...36 BLOK 2: KARCINOM JATER Z RŮZNÝCH ÚHLŮ POHLEDU...42 BLOK 3: ONKOLOGICKÁ PROBLEMATIKA - POHLED ZAHRANIČNÍCH EXPERTŮ...48 BLOK 4: ONKOLOGICKÁ PROBLEMATIKA - POHLED ZAHRANIČNÍCH EXPERTŮ...51 BLOK 5: BIOBANKY...57 BLOK 6: ENDOKRINOLOGIE A VITAMÍN D...62 BLOK 7: MOLEKULÁRNÍ GENETIKA...71 BLOK 8: MELANOM...75 BLOK 9: NOVÉ METODY A SCREENINGOVÉ PROGRAMY

4 Vážené kolegyně a kolegové! Jsem rád, že Vás mohu jménem vědeckého i organizačního výboru přivítat na XXXIX. Imunoanalytických dnech. Hlavními tematickými okruhy letošních Imunoanalytických dnů jsou: Personalizovaná medicína a její aplikace v diagnostice a optimalizaci léčby o Optimální diagnostické algoritmy za využití biomarkerů o Optimální monitorace léčby Biobanky v České republice a jejich propojení do Evropské infrastruktury (BBMRI) o Typy a význam biobank ve zdravotnické praxi o Etické a právní aspekty o Metodické problémy, stabilita, kontrola kvality Metodické problémy stanovení biomarkerů o Nové diagnostické metody o Metody molekulární biologie o Referenční hodnoty o Interpretace výsledků Co nás vedlo k volbě témat? V současné době se často hovoří o "overdiagnostice" a "overterapii". Máme k dispozici obrovskou paletu diagnostických a terapeutických možností a nevyužíváme je optimálně; mnohdy se řídíme pravidlem "čím více, tím lépe" a nerespektujeme přitom, že by naše postupy měly být vždy mezioborově propojeny a koordinovány. Ideálně by měl existoval algoritmus, který umožní stanovení diagnózy, odhad agresivity onemocnění, krátkodobou i dlouhodobou perspektivu průběhu onemocnění včetně návrhu způsobu a rozsahu léčby. A to především v souladu se zájmy a potřebami pacienta. Takto navržené algoritmy umožní optimalizovat individuální přístup k pacientovi a minimalizovat negativní vlivy na jeho kvalitu života. Jaký je cíl konference? Cílem konference je edukace, a obdobně jako v minulých ročnících mají přednáškové bloky vždy multioborový charakter. Komplexně se chceme věnovat dvěma onkologickým problematikám: karcinomu prostaty a karcinomu jater (včetně metastatického jaterního procesu). Kromě toho budou do programu zařazeny další nádorové i jiné problematiky (kardiologické, endokrinologické), kde budou řešeny dílčí problémy. Věřím, že konference poskytne příležitost všem uživatelům a příznivcům imunoanalytických metod k setkáním a pracovním i nepracovním diskuzím s dlouholetými přáteli a partnery. Na setkání s Vámi se těší Prof. MUDr. Ondřej Topolčan, CSc. za organizační výbor a pořádající organizace 4

5 Vědecký výbor konference Vivian Barak Eleftherios P. Diamandis Michael (Joe) Duffy Jindřich Fínek Olga Golubnitschnaja Magadalena Chechlinska Richard Hampl Juraj Kaušitz Reiner Klapdor Judita Kinkorová Rafael Molina Andrea Nicolini Jaroslav Racek Luboslav Stárka Václav Šimánek Ondřej Topolčan Vladislav Třeška Václav Zamrazil Tomáš Zima (Izrael) (Kanada) (Irsko) (Česká republika) (Německo) (Polsko) (Česká republika) (Slovensko) (Německo) (Česká republika) (Španělsko) (Česká republika) (Česká republika) (Česká republika) (Česká republika) (Česká republika) (Česká republika) (Česká republika) (Česká republika) Organizační výbor Ondřej Topolčan Prezident konference Judita Kikorová Vice prezidentka konference Šárka Svobodová Sekretariát Marie Karlíková Sborník abstrakt 5

6 Časový rozvrh 13:00 13:10 Zahájení 13:10 14:15 Plenární přednášky Neděle 11. března 14:15 15:45 Blok 1: Karcinom prostaty z různých úhlů pohledu 15:45 16:15 Coffee break 16:15 17:45 Blok 2: Karcinom jater z různých úhlů pohledu 9:00 10:30 10:30 11:00 Coffee break 11:00 12:30 12:30 13:30 Oběd Pondělí 12. března Blok 3: Onkologická problematika - pohled zahraničních expertů Blok 4: Onkologická problematika - pohled zahraničních expertů 13:30 15:00 Blok 5: Biobanky 15:00 15:30 Coffee break 15:30 17:00 Blok 6: Endokrinologie a vitamín D 17:15 18:00 Panelová diskuze: Perspektivy imunoanalýzy Úterý 13.března 9:00 10:00 Blok 7: Molekulární genetika 10:00 10:40 Blok 8: Melanom 10: Coffee break 11:15 12:15 Blok 9: Nové metody a screeningové programy 12:15 Zakončení 6

7 ODBORNÝ PROGRAM 7

8 NEDĚLE :00 13:10 Zahájení 13:10 14:15 Plenární přednášky The new era of personalized cancer biomarkers Diamandis E., Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada Personalizovaná medicína v onkologii ve FN Plzeň Šimánek V., ředitel FN Plzeň Co můžeme očekávat od imunoterapie? Fínek J., Onkologická klinika a radioterapeutická klinika, FN Plzeň Pohled patologa 14:15 15:45 Blok 1: Karcinom prostaty z různých úhlů pohledu (podpořeno projektem (CZ.1.07/2.3.00/ ) Acinární adenokarcinom prostaty- stanovení prognostických kategorií Hes O., Šiklův ústav patologie, FN a LF Plzeň Pohled laboratorního pracovníka Využití PHI v diagnosticko - léčebném procesu Kučera R., Odd. imunochemické diagnostiky, FN Plzeň Pohled zobrazovacích technik Zobrazení karcinomu prostaty pomocí ligandu PSMA značeného 68-galiem Ferda J., Klinika zobrazovacích metod, FN Plzeň Pohled klinika-urologa Softwarová fúze 3T mp magnetické rezonance a transrektální ultrasonografie (MR/TRUS) při cílené biopsii prostaty Sedláčková H., Urologická klinika, FN Plzeň 8

9 Volná sdělení: Zkušenosti s PHI Čapoun O., Všeobecná fakultní nemocnice Praha Movember s Beckman Coulter Mičíková I., Beckman Coulter 15:45-16:15 Coffee break Pohled patologa 16:15 17:45 Blok 2: Karcinom jater z různých úhlů pohledu (podpořen projektem CZ.1.07/2.3.00/ ) Hepatocelulární karcinom pohled patologa Daum O., Šiklův ústav patologie, FN a LF Plzeň, Bioptická laboratoř s.r.o. Pohled laboratorního pracovníka Biomarkery pro diagnostiku a prognózu nádorového postižení jater Topolčan O., Odd. imunochemické diagnostiky, FN Plzeň PIVKA - nový marker hepatocelulárního karcinomu Svobodová Š., Odd. imunochemické diagnostiky, FN Plzeň Pohled zobrazovacích technik Zobrazení hepatocelulárních ložiskových procesů v jaterním parenchymu pomocí PET/MR Ferda J., Klinika zobrazovacích metod, FN Plzeň Pohled klinika-chirurga Nádorová onemocnění jater Třeška V., Chirurgická klinika, FN Plzeň 9

10 PONDĚLÍ :00-10:30 Blok 3: Onkologická problematika - pohled zahraničních expertů (podpořen projektem CZ.1.07/2.3.00/ ) Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer unknow primary site (CUP) Molina R., Laboratory of Clinical Biochemistry, University of Barcelona, Spain Biomarkers on Ovarian Cancer: Role in Screening, Diagnosis and Management Duffy M., J., St. Vincents University Hospital, Dublin, Ireland 10:30 11:00 Coffee break 11:00 12:30 Blok 4: Onkologická problematika - pohled zahraničních expertů (podpořen projektem CZ.1.07/2.3.00/ ) The individual Reference Limit (IRL) of serum CEA-TPA-CA15.3 tumor marker (TM) panel is cheap,harmless and accurate tool for early detection and treatment of breast cancer metastases Nicolini A., Department of Oncology, University of Pisa, Italy Biomarkers in Cancer Immunotherapy Ferrari P., Department of Oncology, University of Pisa, Italy Exocrine pancreatic cancer - Some case reports suggesting non-optimal use of actual diagnostic and therapeutical tools in clinical routine. Klapdor R., Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany New Mass Spectrometry-Based Technology for Detection of Alcohol Abuse Pompach P., ČSAV, Praha Prostate cancer aggressivness assessment using PSA and TMPRSS2-ERG fusion gene Kučera R., Odd. imunochemické diagnostiky, FN Plzeň 10

11 12:30 13:30 oběd 13:30-15:00 Blok 5: Biobanky (podpořen projekty CZ /0.0/0.0/16_013/ a LM ) BRoTHER: an active platform for knowledge exchange in modern Biobanking Brochhausen C., Univeristy Regensburg, Institute of Pathology, Regensburg, Germany Whole Slide Imaging for an interactive digital pathology framework Brochhausen C., Univeristy Regensburg, Institute of Pathology, Regensburg, Germany Towards standardization of the preanalytical phasebecker K. F., Technical University of Munich, Institute of Pathology, Munich, Germany GDPR: The EU General Data Protection Regulation Hot topic for biobanks Kinkorová J., Odd. imunochemické diagnostiky, FN Plzeň BBMRI ERIC v ČR Valík D., Masarykův onkologický ústav Brno 15:00 15:30 Coffee break 15:30 17:00 Blok 6: Endokrinologie a vitamín D (podpořen projektem CZ.1.07/2.2.00/ ) Je vhodné doplnit léčbu autoimunitních onemocnění kortikoidy nadledvinovými androgeny? Šterzl I, Endokrinologický ústav Praha Biochemie a analytika vitamínu D a jeho metabolitů Bílek R., Endokrinologický ústav Praha D vitamín u těhotných a novorozenců Fuchsová R., Topolčan O., Odd. imunochemické diagnostiky, FN Plzeň 11

12 Necitlivost vůči hormonům skupiny vitaminu D Hampl R., Endokrinologický ústav Praha FGF23 klinický význam Topolčan O., Odd. imunochemické diagnostiky, FN Plzeň Panelová diskuze 17:15 18:00 Perspektivy imunoanalýzy ÚTERÝ :00 10:00 Blok 7: Molekulární genetika (podpořen projektem CZ.1.07/2.3.00/ ) Vyšetření lymfatických uzlin pacientů s plicními nádory pro zařazení do TNM klasifikace metodami H&E, IHC CK19 a OSNA Pešta M, Ústav biologie, LF v Plzni Molecular changes in normal epithelium neighboring endometrial cancer, a field effect? Chechlinska M., Department of Immunology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland Prediktivní význam mir-34a, mir-224 a mir-342 u pacientů s pokročilým karcinomem plic a cerna hypotéza Pešta M., Ústav biologie a Biomedicínské centrum, LF v Plzni 12

13 10:00 10:40 Blok 8: Melanom Biomarkers assess response to new therapies and provide prognosis in Melanoma patients Barak V., Department of Oncology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel Zobrazení okulárního melanomu pomocí 18FDG-PET/MRI Ferda J., Klinika zobrazovacích metod, FN Plzeň 10:40 11:15 Coffee break 11:15 12:15 Blok 9: Nové metody a screeningové programy (podpořen projektem CZ.1.07/2.2.00/ ) Zkušenosti s 1h algoritmem v diferenciální diagnostice bolestí na hrudi Rajdl D., Oddělení klinické biochemie, FN Plzeň Využití multiplexových metod v klinické praxi a výzkumu Karlíková M., Odd. imunochemické diagnostiky, FN Plzeň Screeningové programy v těhotenství Springer D., Odd. klinické biochemie, VFN, Praha Referenční hodnoty Topolčan O., Odd. imunochemické diagnostiky, FN Plzeň zakončení konference 13

14 VYZVANÍ ŘEČNÍCI 14

15 Vivian Barak, M.D., Ph.D. Professor Prof. Barak received her Ph.D. in Immunology at Hebrew University-Medical School in Jerusalem, Israel. Since 1985 Dr. Barak is a Head of Immunology & Tumor Diagnosis Lab, Oncology Dept, Hadassah Medical Center, Jerusalem. Between she worked as a lecturer in Oncology at Hebrew University -Medical School in Jerusalem and since 2005 she is an Associate Professor in Oncology, Hebrew University- Medical School, Jerusalem. Prof. Barak is a Head of Israeli Cytokine Standardization Laboratory and Israeli Tumor Markers Standardization Laboratory. Prof. Barak is a member of editorial boards of international journals and a board member in 13 international societies, she was a member of 30 scientific committees of international conferences. She held presidential positions at 5 international congresses (IATMO, ISOBM four times). In 2017 Prof.. Barak was the recipient of the ISOBM ABBOTT Award. Author/co-author of 264 papers in international journals and 16 papers in Israeli journals. H-index 44. Karl-Friedrich Becker, Ph.D. Professor Institute of Pathology, Technische Universität München, Trogerstrasse 18, München D-81675, Germany, kf.becker@tum.de Dr. Becker heads the Laboratory for Experimental Pathology at the Technical University of Munich, Germany. His lab uses unique methods for protein analysis of tissues, e.g. extraction of intact proteins from formalinfixed and paraffin-embedded (FFPE) tissues and Reverse Phase Protein Arrays (RPPA), for which he was awarded with the Novartis Research Prize for Pathology. Since 2012 Prof. Becker is member and project leader of the European Committee for Standardization (CEN) TC140 In vitro diagnostic medical devices, WG3 Quality Management in the Medical Laboratory and since 2014 member and project leader of the International Organization for Standardization (ISO) TC212 Clinical laboratory testing and in vitro diagnostic test systems. Since June 2016 Dr. Becker is Scientific Director of the Tissue Biobank of the Medical School of the Technical University of Munich. 125 publications listed in PubMed 8861 citations H-index: 46 15

16 Ing. Radovan Bílek, Ph.D. Associate Professor Dr. Bílek got a PhD. degree in biochemistry at the University of chemistry and technology in Prague. Since 1991 he is a researcher at the Endocrinology Institute in Prague. In he was a head of the Department of proteohormones and biofactors; in 2010 the Department merged with the Dpt. of steroid hormones and became Department of steroid and proteofactors where Dr. Bílek works as an R&D expert. Dr. Bílek is registered at the Ministry of Health, Czech Republic, as a healthcare expert specialised on analytical methods in chemistry and toxicology. He completed a one-year internship as a researcher in National Institute for Medical Research, London, UK. Dr. Bílek has been teaching instrumental analysis at several Czech universities. He was a member of the Scientific commitee 4 (chemistry) of the Funding agency of Czech Academy of Science. He is a member of European thyroid association. Dr. Bílek participates in the solution of iodine deficiency in Czech Republic and in the research dealing with medular thyroid carcinoma and multiple endocrine neoplasia syndrom including feochromocytom. He published and presented more than 300 works. Christoph Brochhausen, M.D. Professor Institute of Pathology, University Regensburg, Franz Josef Strauß Allee 11, Regensburg, D-93053, Germany, christoph.brochhausen@ukr.de Dr. Brochhausen is Vice Director of the Institute of Pathology at the University Regensburg. Since 2018 he holds a professorship for pathology at the University Regensburg focusing on Digital Pathology, Tissue Banking and Tissue Engineering. His lab uses modern techniques in digitalization and engineering, e.g. Whole Slide Imaging, three dimensional image reconstruction, and in vitro modelling, for which he was awarded with the Ars legendi Award of the German Medical Faculty day (2015), the Histalim Award (2015) and as a landmark in the Land of Ideas (2012). Since 2015 Dr. Brochhausen is member of the German Committee of Standardization ( Biobanks and Biorepositories ). Since 2018 Dr. Brochhausen is head of the Central Biobank of the University Regensburg. 130 per-reviewed articles 1700 citations H-index: 23 16

17 Eleftherios P. Diamandis, MD., PhD. Professor Dr. Diamandis currently serves as Division Head of Clinical Biochemistry at Mount Sinai Hospital and Biochemist-in-Chief at the University Health Network and is Professor & Head, Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. His research activities evolve around discovery and validation of cancer biomarkers, proteomics, mass spectrometry and translational research. Dr. Diamandis received his B.Sc. in Chemistry, Ph.D. in Analytical Chemistry and M.D. from the University of Athens, Greece and a Diploma in Clinical Biochemistry from the University of Toronto, Canada. He is a Certified Clinical Chemist by the Canadian Academy of Clinical Biochemistry and the American Board of Clinical Chemistry. Dr. Diamandis is a Member of 45 Journal Advisory Scientific and Editorial Boards. He has received numerous awards from both national and international organizations He has more than 51,000 lifetime citation and an H-index of 112. Other major distinctions of Dr. Diamandis include his election as Corresponding Member of the Academy of Athens, Greece (2005), Member of the Royal Society of Canada (2008). Fellow of the American Association for the Advancement of Science (2011) and Fellow of the Canadian Academy of Health of the Sciences (2012). He has published 150 review papers, over 600 research papers and co-authored 4 books and 42 book chapters. He is the inventor of 28 issue and 26 pending patents and supervised 22 MSc. and 42 PhD. theses. The research interests of Dr. Diamandis are as follows: 1. Kallikrein Biology and Pathophysiology 2. Proteomics 3. Tumor Markers 4. Mechanisms of Carcinogenesis and Metastatic Progression 5. Translational Research 6. Cancer Therapeutics 7. Male Infertility 8. Pathobiology and Biomarkers of Autoimmune Diseases 9. Neurodegeneration 17

18 Ondřej Daum, M.D., Ph.D. Associate Professor He graduated from Charles University, 1 st Faculty of Medicine in Prague in He took a Ph.D. degree in 2007 at Charles University, Faculty of Medicine in Pilsen with the doctoral thesis: Differential diagnosis of spindle cell lesion of the digestive tract. In 2012 he finalized and defended his habilitation work on the topic Differential diagnostics of mesenchymal tumor of the digestive tract and took the degree of associate professor. In 1998 he started to work in the Department of Pathology in the District Hospital of Cheb. Since 1999 he has worked as a pathologist in the Sikl s Institute of Pathology of the University Hospital in Pilsen. Since 2004 he has also worked as an assistant professor of Faculty of Medicine in Pilsen. Since 2007 he has worked as a consultat in Biopticka laborator s.r.o. in Pilsen. Nowadays, he works as head of the Department of Bioptical and Autoptical Laboratory Bory of the Sikl s Institute of Pathology at the University Hospital and Faculty of Medicine in Pilsen. He participates in research regarding gastrointestinal, hepatobiliary and endocrine pathology. He is a member of the European Society of Pathology (ESP), and International Academy of Pathology (IAP). He is an author of 90 articles in medical journals with more than 320 citations in available literature, H-index 9. M Joe Duffy, M.D., Ph.D. Professor Prof. Duffy who is based at St Vincent s University Hospital, Dublin and University College, Dublin has extensive experience in oncological molecular therapeutics and biomarkers. He has published in excess of 250 papers on these topic, including articles in high impact journals such as Lancet, BMJ, J Natl Cancer Instit, Cancer Res, Clin Cancer Res, Ann Oncol and Clin Chem. His work has been cited > 16,000 times and his currently H-index is 71. In 2012, Prof. Duffy was the recipient of the 2012 Abbott Award of the International Society of Oncology and BioMarkers (ISOBM). This award is made annually to investigators, world-wide, who have made an outstanding contribution in the field of basic or clinical oncology research. Other awards received by Prof. Duffy include the St Luke s Medal Lecture, the Conway Review Medal Lecture and the Lifetime Achievement Award of the Royal Academy of Medicine in Ireland and the National Committee for Biochemistry Award Medal Lecture of the Royal Irish Academy. 18

19 Dr. Paola Ferrari Dr Paola Ferrari graduated in Medicine and Surgery at Pisa University in 1995 (full marks), specialized in Internal Medicine in 2000, PhD in Medical Physiopathology and Pharmacology. She works as medical oncologist at Unit of Oncology 1, Department of Oncology, New Technologies and Transplantations, University of Pisa. Clinical activity: follow-up and therapy of cancer patients, mainly breast cancer patients. Principal fields of research: breast and gastrointestinal cancer follow-up and therapy, breast cancer biomarkers and prognostic factors, cancer immunology, circulating tumor cells, cancer stem cells. Dr Paola Ferrari is author/co-author of about 50 articles in peer reviewed journals. She regularly serves as reviewer for international oncology journals. Jiří Ferda, M.D., Ph.D. Professor Dr. Ferda graduated from Charles University, Faculty of Medicine in Pilsen. Current positions: Professor of Radiology Charles University, Faculty of Medicine in Pilsen Deputy head of Dpt. of Imaging Methods, University Hospital Pilsen Lead of Molecular Imaging Unit Vice-dean for education Charles University, Faculty of Medicine in Pilsen President of the Czech Radiological Society Medical specialty: Radiology I st an II nd level, Neuroradiology, Vascular Interventional radiology, Nuclear Medicine Main professional orientation: advanced imaging of cardiovascualr sysem, onkology, molecular imaging, hybrid imaging. His scientific citation index is 727 and H-index is

20 Jindřich Fínek, M.D., Ph.D. Professor Prof. Fínek graduated from Medical Faculty in Pilsen, Charles University, in 1986 he obtained his 1st degrese specialisation in radiotherapy, in 1989 the 2nd degree specialisation in radiotherapy and in 1992 specialisation in medical oncology. Since 1983 he has been working at Oncology and Radiotherapy Clinic at University Hospital Pilsen, since 1995 to present he is Senior Consultant, between 1996 and 2005 he worked as asistent professor, as associate professor in the field of oncology and 2012 to present he is professor of oncology at Faculty of Medicine in Pilsen, Charles University. He is a member of international and national medical societies e.g. of the Comprehensive Cancer Center at University Hospital in Pilsen, Member of interdisciplinary and interdepartmental commission for the Ministry of Health of the Czech Republic and orphan drugs, Member of the American Society of Clinical Oncology (ASCO), the representative of the Czech Republic in EU activity The Burden of Cancer, how it can be Reduced in Luxembourg, chairman of the co-operative Group for the treatment of malignant neoplasms and research non-profit organization. His scientific citation index is 636 and H-index is 13. Since 2018 prof. Fínek is dean of Faculty of Medicine in Pilsen, Charles University. Radka Fuchsová, M.D. Physician, Department of Immunoassay Laboratory, University Hospital in Pilsen; Researcher, Central Isotope Laboratory, Faculty of Medicine Pilsen, Charles University Prague. Graduate of Charles University Faculty of Medicine in Pilsen. Medical specialisations: Immunoassay methods for the detection and quantification of biologically important substances; interpretation of laboratory results; clinical consultation in the fields of endocrinology, tumour and bone markers. Scientific and research activities: Currently participating in Faculty of Medicine and University Hospital in Pilsen grant projects in the fields of prevention, early diagnosis and personalised medicine focused on biomarkers in oncology, endocrinology and preventative cardiology. Concerned with quality control of immunoassays and external quality control of hormone testing. Post-graduate student, thesis on vitamin D. Publications and lectures: Author and co-author of twelve original reviewed articles. Frequent lecturer at regional and national conferences. Teaching activities: Lecturer, Education for Competitiveness operational programme OPVK 2.2 Endocrinology: Multidisciplinary course for physicians and university researchers and OPVK 2.3 Molecular genetics of neoplastic and cardiovascular diseases. Her scientific citation index is 75 and H-index is 6. 20

21 RNDr. Richard Hampl, DrSc. Professor Since 1958 he has been employed in the Department of Steroids at the Institute of Endocrinology. Since 1983 he has been a Head of the Department of Steroid Hormones at the Institute of Endocrinology. In 1991 he defended his doctoral dissertation "Interaction of Steroids with Specific Proteins", in 1999 he was habilitated at the Faculty of Natural Science, in 2006 he became a professor. Prof. Hampl is a recognized expert in the field of biochemistry and steroid hormone analyzes. It deals with the development of immunoanalytical methods of determination of steroids and their applications in endocrinology as well as with questions about the mechanism of action of steroids. In these areas, he cooperates with a number of Prague clinics of all three faculties of medicine and with the Faculty of Natural Sciences of the UK, as well as with foreign departments (Paris, London, Helsinki). His long-term cooperation with the National Endocrinology and Diabetology Institute in Lubochna, Slovakia is extremely fruitful. He is the author and co-author of over 340 publications and chapters in monographs, of which almost half are abroad. He is regularly invited as a lecturer at international conferences and endocrinological congresses. Ondřej Hes, M.D., Ph.D. Professor Dr. Hes graduated from Charles University, Medical Faculty in Plzen in In 1996 passed 1 st degree Board Certificate in Pathology, in 1999 passed 2 nd degree Board Certificate in Pathology, both in Prague. He took a Ph.D. degree in 2001 at Charles University Medical Faculty in Pilsen with doctoral thesis: Rare renal tumors. In 2003 dr. Hes defended habilitation work and was designated as Associated Professor and in 2009 was designated as Professor of Pathology (both Charles University). Dr. Hes started his carier in 1993 in Department of Pathology, Charles University Hospital and Medical Faculty in Plzen and he works nowadays as head of Laboratory of Special Diagnostics (Department of Pathology, Charles University Hospital and Medical Faculty in Plzen). Dr. Hes is member of following working groups: 2011: Member of working group Classification of Renal Tumors, International Society of Urogenital Pathology (ISUP), 2015: WHO-blue book: Kidney Tumours, 2015: ENUP (European Network of Urogenital Pathology) steering group. Dr. Hes published more than 320 papers according Medline (February 2018), has more than 3500 citations according Web of Science (February 2018), and his H index is 28 (February 2018). 21

22 Dr. Hes is author of one monography, co-author of another monography (both published in Czech) and author/co-author of several chapters in different monographies published in Czech and English. Since 2016 dr. Hes is Head of Training Center of European Society of Pathology (programme Giordano, GU pathology). He is member of 6 editorial boards. Dr. habil. Magdalena Chechlińska Professor Dr. Chechlinska is head of Department of Immunology at the Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, Poland. She has published on cancer microenvironment, cytokines, micrornas, with a special emphasis on biomarker search. In 2011, she was awarded the The Jedrzej Sniadecki Memorial Award of the Medical Department of the Polish Academy of Sciences for a series of papers on cancer biomarkers. She serves on the Editorial Board of BMC Cancer and Contemporary Oncology. She is a member of several Polish and International professional societies. She has been an invited speaker at a number of national and international conferences. RNDr. Marie Karlíková, Ph.D. Dr. Karlíková has a Master degree from Charles University, Faculty of Natural Sciences (1995) and a D.E.S.S. degree from University of Strasbourg (Environmental sciences, 1996). She got a Ph.D. degree in 2004 at Charles University, Faculty of Natural Sciences (Analytical chemistry). During her postrgraduate studies, she obtained several scholarships, namely at Karolinska Institut, Stockholm, University of Natural Resources and Life Sciences, Vienna. and Institut of Clinical Chemistry, Ludwig Maxmilian University, Munich. Since 2008 she has been working in the Department of Immunochemistry of Charles University, Faculty of Medecine in Pilsen and University Hospital Pilsen as a researcher and lecturer. In she was a project manager of two EU-funded projects focused on the education of university students and professionals in the field of immunoanalytical methods and personalised medicine. Currently Dr. Karlíková participates in several research projects focusing on multiplex immunoassays and their use in biomedical research.she is a member of Biobank Pilsen team, dealing with the optimisation of specimen storage and long-term stability of biomarkers. She is author/co-author of about 20 papers. Her scientific citation index is 64 and H-index is

23 RNDr. Judita Kinkorová, Ph.D. Associate Professor Dr. Kinkorová is currently the manager of international research cooperation and affairs at University Hospital in Pilsen and Faculty of Medicine in Pilsen, Charles University. She is a manager of the Biobank in Pilsen that is a member the biggest EU infrastructure, Biobanking and BioMolecular resources Research Infrastructure (BBMRI-ERIC) in Pilsen. Her main areas of interest are personalized medicine, biobanking and biomarkers. Dr. Kinkorová studied Charles University in Prague, specialization biology-mathematics, holds a Ph.D from Czech University of Life Sciences in Prague. She worked at Charles University, Faculty of Natural Sciences as a teacher and researcher, from 2007 as National Contact Point (NCP) for FP7, priority Health, and in 2014 Horizon 2020 societal challenge SC1 Health, demographic change and wellbeing at the Academy of Sciences of the Czech Republic, since 2015 is full employee in Pilsen (University Hospital and Faculty of Medicine in Pilsen). Dr. Kinkorová is involved in BRoTHER Czech Bavarian cross border biobanking project. Dr. Kinkorová is a member of EPMA (European Association for Preventive, Predictive and Personalized Medicine), ISOBM (International Society of Oncology and BioMarkers), EGTM (European Group of Tumor Markers), EBSS (European, Middle Eastern and African Society for Biopreservation and Biobanking), ISBER (International Society for Biological and Environmental Repositories). Dr. Kinkorová is the author of 40 publications. Rainer Klapdor, M.D. Professor Prof. Klapdor is specialized in internal medicine with concentration to gastrointestinal physiology and oncology. The scientific work started in the middle of seventies with studies on bile acid metabolism, then changing to studies on enterohepatic circulation and gastrointestinal hormones and later to diagnosis and therapy of endocrine and exocrine tumors of the biliarypancreatic axis. Since 1983 he is active in increasing work on tumor markers and organization of the Hamburg Symposia on Tumor markers (HSTM) regularly organised every year. Prof. Klapdor recieved several scientific awards and is a members in many professional societies. 23

24 Radek Kučera, PharmDr., Ph.D. Associate Professor He graduated from Charles University, Faculty of Pharmacy in Hradec Kralove in 1991 with the dissertation on the topic Determination of digoxin using radioimunoanalytic methods. He took a Ph.D. degree in 2011 at Charles University, Faculty of Medicine in Pilsen with the doctoral thesis: Insuline like and other growth factors and tumors. In January 2017 he finalized and defended his habilitation work on the topic Insulin like growth factor I in theory and clinical practice and took the degree of associate professor. In 1991 he started to work in the Department of Nuclear Medicine in the District Hospital of Klatovy. Since 2011 he has worked as an external lecturer of Faculty of Medicine in Pilsen. Since 2013 he has worked in the Department of Immunochemistry in University Hospital Pilsen. Nowadays, he works as vice head of the Department of Immunochemistry and teaches biochemistry at the Faculty of Medicine in Pilsen. He participates in research regarding hormones, growth factors and tumor markers. He is a member of the International Society of Oncology and Biomarkers (ISOBM). He is the author of more than 50 articles in medical journals with more than 130 citations in available literature, H-index 7. Rafael Molina, M.D., Ph.D. Professor Graduate in Medicina (University of Barcelona in 1979) and specialist on Clinical Pathology (Hospital Clinic 1983). In 1989 Dr Molina was Assistant Professor in the Department of Oncology, Health Science Center at San Antonio, Texas. Since 1996 is Assistant Professor of Biochemistry and Molecular Biology of the University of Barcelona and from 2002, president of the Biochemist Section of the Catalonian Academy of Medical Sciences. Dr. Molina is President and Board member of the ISOBM (International Society of Oncodevelopmental Biology and Medicine) and member of the editorial board of Tumor Biology, Journal of Biological Markers and Clinical Biochemistry. Likewise, Dr. Molina is the Chairman an active member of the European Group on Tumor markers (EGTM) and has been contribute to the publication of guidelines about the tumor marker use in Breast cancer and lung cancer in this group and in the NACB (National Academy of Clinical Biochemistry). He is member of the organizing committee of 18 International Congress or Symposiums and 20 courses about the clinical use of tumor markers. Dr. Molina is working in laboratory oncology from 1983 and is author of 175 original articles. 24

25 Andrea Nicolini*, M.D. Aggregate Professor at Department of Oncology, Pisa University, Pisa, Italy. *retired from Academy His research over the past 20 years was mainly devoted to the field of breast and colorectal cancer, particularly the use of serum tumor markers in the "early" detection and treatment of metastatic disease and the function of cell mediated immunity. The role of immunotherapy combined with conventional antiestrogen therapy to overcome the arising of resistance in endocrine dependent metastatic breast cancer was another main explored research field. Dr.Nicolini has published about 250 original papers/review articles (including book chapters), most of them in peer reviewed Journals with I.F. He takes part of the Editorial Board of a few high rank scientific Journals and regularly serves as reviewer for them and many others. RNDr. Martin Pešta, Ph.D. Associate Professor Dr. Pešta is a member of Czech Society for Biochemistry and Molecular Biology (CSBMB). He was appointed as the Head of the Department of Biology, Faculty of Medicine in Pilsen, Charles University in He was born in 1976 in Pilsen, studied biology focused on immunology at Faculty of Science, Charles University, and graduated in In 2002 he started his doctoral studies at Faculty of Medicine in Pilsen, Charles University, focused on colorectal carcinoma, and graduated in In 2016 he was appointed Associate Professor with the thesis entitled: Selected predictive and prognostic markers of solid tumors monitoring at the level of RNA expression. He has long time experience in molecular diagnostics and immunology. He worked in Molecular Diagnostics laboratory, Radiological Clinic, Friedrich- Wilhelms-University of Bonn, SRN and at Education and Research Centre, St Vincent s University Hospital, University College Dublin, Elm Park, Dublin, Irsko. His actual work mainly deals with predictive and prognostic markers of oncological diseases, and cardiovascular diseases. Citations: 422, H-index:

26 Petr Pompach, Ph.D. Petr Pompach is scientist in charge in the Institute of Biotechnology of the Czech Academy of Sciences and research assistant at Department of Biochemistry, Charles University in Prague. He is a member of the executive board of the Czech Society for Mass Spectrometry and co-founder of the AffiPro company. His research activities are focused on detection and quantification of serum glycoproteins by mass spectrometry. He spent two years as a postdoctoral fellow at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, where he was monitoring glycopeptides changes in hepatocellular carcinoma. Petr Pompach is a co-developer of the technology for surface modification by reactive ion landing under atmospheric pressure. This technology was successfully used for enrichment of clinically important antigens from human serum followed by MALDI mass spectrometric detection. Petr Pompach is author of more than 40 articles and co-author of national, European and US patents. Daniel Rajdl, M.D., Ph.D. Dr.Rajdl graduated from the Medical Faculty in Pilsen, Charles University, in 2001 and obtained his Ph. D. in From 2009 he has specialized qualification of medical doctor in clinical biochemistry ( European attestation ). He works as a medical doctor, scientist and teacher at Department of Clinical Biochemistry and Hematology, Medical Faculty in Pilsen and University Hospital. His research topics are dedicated to risk factors of atherosclerosis and biomarkers of organ damage. He has published more than 40 scientific articles and his H-index is 9. He is a member of Continuous Postgradual Development Board of Charles University and a chair of EFLM Workgroup for Distance Education and E-learning. Hana Sedláčková, M.D. I am a doctor of the Department of Urology, University Hospital in Pilsen. I graduated from the Faculty of Medicine in Pilsen, Charles University. Urology has already received me as a medical student, so I attended the Urology Clinic since the fourth year. I attended most of the surgeries, learned ultrasonography and watched the work in the doctor's office. Therefore, choosing a job at the sixth year was a clear choice. Nowadays, I am a Ph.D. student in the doctoral study program of surgery. I focus on prostate cancer, more precisely on its new diagnostic methods. 26

27 Ing. Drahomíra Springer, Ph.D. Associate Professor She graduated on the University of chemical technology, major biochemistry in 1985 and PhD study completed at First Faculty of Medicine, Charles University in Prague. She is the head of endocrinology part of Institute of Clinical Biochemistry and Laboratory Diagnostics, University Hospital Prague. Since 2016 is an assistant professor on the First Faculty of Medicine, Charles University. Her research topics are tumour markers and screening methods in pregnancy (Down Syndrom and thyroid diseases). Dr. Springer is a member of the Czech Society of Clinical Biochemistry and International Society for Oncodevelopmental Biology and Medicine. She is the author of minimally 25 original papers, 3 chapters in monograph and presentation on both international and Czech scientific meetings. She is editor of 2 monographs. Šárka Svobodová, M.D., Ph.D. She graduated at 1 st Medical Faculty in Prague in During her studies she spent one year at UTHSCSA in San Antonio, Texas. She obtained the Internal Medicine 1 st degree specialization in 1998 and the licence for Internal Medicine in She worked as a resident at the 1 st Internal Medicine Clinic, General University Hospital, Prague at the Department of the emergency medicine until Since 2002 she has been working as an Internal Medicine Specialist at the 3 rd Internal Medicine Clinic, General University Hospital, Prague: particularly at Outpatient Clinic dedicated to metabolic syndrome and diabetes. She took a Ph.D. degree in 2009, with the doctoral thesis: Regulation of parameters of biological activity of colorectal cancer. She is currently an assistant professor at the 1st Medical Faculty Charles University in Prague and at the Medical Faculty Charles University Pilsen, participating on issue of immunoanalytical methods. She is a member of European Association for Predictive, Preventive & Personalized Medicine EPMA She has published more than 40 publications in medical journals. Her scientifically citation index:is 160 and H-index 9. 27

28 Václav Šimánek, M.D., Ph.D. Dr. Šimánek graduated from Charles University, Faculty of Medicine in Hradec Králové, he took his PhD degree at Faculty of Medicine in Pilsen, Charles University in Between 1994 and 2005 he worked at Department of Surgery in Hospital Liberec and between 1995 and 1997 at Department of Neurosurgery University Hospital Pilsen. After obtaining surgery 1st degree specialisation in 1997 he started to work at Department of Surgery University Hospital Pilsen. Next 2nd degree specialisation in surgery obtained in 2002 and later in 2008 in traumatology. Since 2003 he has been lecturing at Faculty of Medicine in Pilsen, Charles University. Since 2014 he is Director of University Hospital Pilsen. Ivan Šterzl M.D., Ph.D. Professor of imunology In 1979 he graduated from the 2 nd Faculty of Medicine, Charles University and then joined the Endocrinology Institute in Prague. After six years he gained the rank of candidate in medical science in physiology (PhD) and 2001 as doctor in medical science in immunology. In he worked as a visiting scientist at the neuro-immuno-endocrinological group of the physiological department of the South Western Medical Center at Dallas USA. In he worked as a consultant at the Institute of Microbiology at Birmingham University in Alabama USA, in the Department of Immunology at prof. Jiri Mestecky. In 1997 he was habilitated and after four years he became the director of the newly established Institute of Immunology and Microbiology of the First Faculty of Medicine and General Teaching Hospital in Prague ( ). Professor of immunology was appointed in He has a national attestation in the fields of internal medicine, endocrinology and clinical immunology and alergology. He was twice awarded the Czech Ministry of Health, for successful research projects (in 2005 and 2009). He is also the holder of Prize for the Best Publication (2006) of the Czech Medical Society of Jan Evangelista Purkyne (CLS JEP) and the Prize of Professor Karel Raska for the Best Publication (2007). 2009, he was awarded the Best Monograph of the Year "Endocrine Orbitopathy" from the Czech Endocrinology Society of CLS JEP. In 2017 the he was awarded for the best publication for 2016 Czech and Slovak Society of Otorhinolaryngology and Head and Neck Surgery. Publications: 4 monographs, 7 chapters in books, 315 publications in international and local Journals, 175 communications in conference. Grants from 1990 Applicant/coapplicant in 18 grant project and 2 international grant projects. SCI Citations 811, H- index

29 Ondřej Topolčan, M.D., Ph.D. Professor Prof. Topolčan graduated from the Faculty of Medicine in Pilsen, Charles University in Since 1993 he is a professor at the Faculty of Medicine in Pilsen, Charles University. He worked as a Head of 2 nd Department of Internal Medicine in University Hospital in Pilsen ( ). Since 2000 he has been working as a Head of the Central immunoanalytic and research laboratory of the Faculty of Medicine in Pilsen. Since 2017 he is a Head of Department of imunochemistry at the University hospital in Pilsen. He was a member of Scientific committee of the Faculty of Medicine in Pilsen ( ). Since 2009 he is a member of Scientific committee of Endocrinology institut in Prague. Since 2001 he is a Deputy director for research and science at the University hospital Pilsen. In 2011 he was awarded by Carl R. Jolliff Award for Lifetime Achievement in Clinical and Diagnostic Immunology by the American Association for Clinical Chemistry (AACC). He is a member of European Group on Tumor Markers EGTM, of International Society of Tumor Markers and Molecular Biology ISOBM and of European Association for Predictive, Preventive & Personalized Medicine EPMA. Prof. Topolčan has published more than 300 publications in medical journals and presented more than 410 lectures in medical conferences and congresses. His scientific citation index is and H-index is 23. Vladislav Třeška, M.D., DrSc. Professor Since 1999 Prof. Třeška is Head of Surgery Clinic - Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, and also head of Transplantation Centre. He is a vicedean at Faculty of Medicine in Pilsen. He spent research fellowship in Nottingham, Pitsboug and Hongkong. In his 40 years he was the youngest professor of surgery in the Czech Republic. Prof. Třeška is secretary general of European Society of CardioVascular Surgery (ESCVS), deputy chairman of the Czech Society of Surgery JEP, scientific secretary of the Czech Society of Cardiovascular Surgery JEP, honest member of the Slovak Society of Surgery, member of academic council Charles University in Prague and Faculty of Medicine in Pilsen. He is author of 381 scientific publications, 783 presentations, and he is author or coauthor of 23 monographs. His scientific citation index is 1933 and H-index is 22. He was awarded in 1997 the award of the Medical Society in Pilsen, in 1999 the Prusík Price in the field of angiology, in 2002 the Rector Price of Charles University for his monograph Transplantology for medical students and in 2011 he became Icon of town Pilsen. 29

30 Dalibor Valík, M.D., Ph.D. Associate Professor Dr. Valík is Head of the Department of Laboratory Medicine at the Masaryk Memorial Cancer Institute in Brno. He received his MD in 1985 from the Faculty of Medicine of Masaryk University in Brno and PhD degree in Biochemistry and Pathobiochemistry from the First Faculty of Medicine of Charles University in Prague in Dalibor Valík is respected authority on biochemistry and oncology. His main interests are focused on the research in hereditary metabolic disorders and its relation to the variable response of individual patients to antitumor chemotherapy. Dalibor Valík is coordinator of RECAMO (Regional Centre for Applied Molecular Oncology). Masaryk Memorial Cancer Institute is coordinating institution of the Czech node of European project BBMRI_CZ (Biobanking and BioMolecular resource Research Infrastructure), from FP7 (Framework programme 7), and Dr. Valik is the national coordinator. 30

31 ABSTRAKTA 31

32 Plenární přednášky The new era of personalized cancer biomarkers Diamandis E., Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada Personalizovaná medicína v onkologii ve FN Plzeň Šimánek V., ředitel FN Plzeň Co můžeme očekávat od imunoterapie? Fínek J., Onkologická klinika a radioterapeutická klinika, FN Plzeň 32

33 The new era of personalized cancer biomarkers Eleftherios P. Diamandis 1,2,3 1 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada 2 Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada 3 Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada *To whom the correspondence should be addressed: Eleftherios P. Diamandis, MD, PhD, FRCP(C), FRSC Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network 60 Murray St. Box 32, Floor 6, Rm L6-201 Toronto, ON, MST 3L9, Canada Tel. (416) Eleftherios.diamandis@sinaihealthsystem.ca Background and aim Cancer biomarkers are important for cancer patient management. Most clinically used cancer biomarkers were discovered years ago. No new biomarkers have entered the clinic recently, with the exception of molecular biomarkers that are mainly used for selection of therapy. We here propose new ideas for utilizing a plethora of cancer biomarkers which work for only for a small portion of patients (rare biomarkers). Patients and methods We will provide examples of 5-10% of patients with pancreatic cancer who have elevated circulating serum biomarkers that have not been described before. We will then propose a scheme for screening of thousands of candidate biomarkers, to select a few that work best for a small number of patients. Results We propose a method for identifying personalized cancer biomarkers. These biomarkers are circulating proteins or circulating tumor DNA. We will discuss the utility of circulating tumor DNA for various clinical applications, including patient management and early detection. Conclusion Personalized biomarkers can now be identified with high throughput techniques and utilized to optimize cancer patient treatment 33

34 Personalizovaná medicína v onkolologii Václav Šimánek ředitel Fakultní nemocnice Cílem prezentace je zodpovědět na následující otázky: Proč zavádíme personalizovanou medicínu v onkologii - Definice a základní charakteristika personalizované medicíny - Historický vývoj personalizované medicíny Jak realizujeme - Z jakých existujících předpokladů vycházíme - Jak realizujeme v diagnostice - Jak realizujeme ve volbě, optimalizaci a monitoraci léčby Co očekáváme Přínos pro nemocného Přínos pro Fakultní nemocnici Zapojení do mezinárodní spolupráce Jaké jsou naše plány a perspektivy vývoje Co bude dál 34

35 Co můžeme očekávat od imunoterapie? Jindřich Fínek Onkologická a radioterapeutická klinika, Fakultní nemocnice Plzeň Existuje velké množství klinických dat, která ukazují, že prognóza pacientů, jejichž nádor je infiltrován buňkami imunitního systému, je příznivější než u prognóza pacientů, jejichž nádory infiltrovány nejsou... Počátky protinádorové imunoterapie spadají do r. 1891, kdy dr.coley podal pacientovi s nevyléčitelným sarkomem dávku streptokoků s představou, že imunitní obrana proti tomuto nebezpečnému mikroorganismu by mohla jako vedlejší efekt zasáhnout i nádor... Sir MacFarlane Burnet, později oceněný Nobelovou cenou, vyslovil v r hypotézu, že fyziologickou úlohou imunitního systému je rozpoznat pro organismus potenciálně nebezpečné buňky, včetně buněk nádorových, a zlikvidovat je pomocí efektorových mechanismů jak vrozené, tak získané imunity. Fakt, že je imunitní systém důležitý pro kontrolu nádorových buněk, ukazují jasně data týkající se vyššího výskytu nádorů u zvířat s nefunkčním imunitním systémem nebo u pacientů s oslabeným imunitním systémem (HIV, transplantace...) V polovině 70. a začátkem 80. let minulého století byla pacientům byla podávána živá BCG vakcína známá jako bacillus Calmette Guérin nebo Corynebacterium parvum. Bakterie aktivují makrofágy pacienta a tím umožňují makrofágy zprostředkované zabíjení nádorových buněk. Kromě toho fungují i jako adjuvans a podporují T buněčnou reakci na nádorové antigeny. V 70. letech minulého století se ukázalo, že vysoké dávky IL-2, růstového faktoru pro T-lymfocyty, byly účinné při podání pacientům s pokročilými metastatickými nádory... Tato data nakonec vedla FDA ke schválení IL-2 pro léčbu pacientů s metastatickým RCC v r a s metastatickým melanomem v r U části pacientů docházelo k trvalým CR (5-10% pacientů) a tyto odpovědi trvají u některých pacientů už více než 20 let po ukončení IL-2... Pak už následovala éra moderní imunoterapie. 35