3rd ITLT Essen 2013 3rd ITLT Essen 2013 3rd ITLT Essen ... › media › document › 2254 › 13-04-18-20... · Room New York Bayer Healthcare Deutschland / Bayer Consumer Care Bayer

18 – 20 April 2013Congress Center Essen

3rd ITLT Essen 2013Interdisciplinary Treatment of Liver Tumors





www.itlt.org

Under the auspices ofIn cooperation with the Academy for Continuing Medical Education in Radiology

CAO-V Chirurgische Arbeitsgemeinschaft für Onkologie

ITLT - 2013

Delcath cordially invites you to attend a Breakfast Symposium

Evolution of Chemosaturation Therapy: A New Paradigm for Treating Whole Organ Liver Metastases

Special 45 minute event:Friday, 19. April 2013 8:00am – 8:45am Mailand Room

Moderated by: Jonathan S. Zager, MD, FACS Director of Regional Therapies Associate Member Department of Cutaneous Oncology Sarcoma Program Moffitt Cancer Center, Florida

8:00 – 8:10 Concentrated Chemotherapy to the Liver: The History of Chemosaturation Jonathan S. Zager, MD, FACS Director of Regional Therapies Associate Member Department of Cutaneous Oncology Sarcoma Program Moffitt Cancer Center, Florida

8:10 – 8:20 CHEMOSAT® Procedural Steps Christoph Engelke, MD Professor of Radiology Vice Chairman, Department of Radiology Georg August University of Goettingen, Germany

8:20 – 8:30 Setting Up a CHEMOSAT® Programme at Your Hospital Thomas J. Vogl, MD Director of the Institute for Diagnostic and Interventional Radiology Johann Wolfgang Goethe-Universität Frankfurt, Germany

www.chemosat.comPlease visit us at ITLT booth F.01

Delcath’s Hepatic CHEMOSAT Delivery System is CE Mark approved in Europe. In the United States, the chemosaturation system is an investigational product and has not received FDA approval.






Contents

Greetings ..................................................................................................... 4

Scientific Program Overview ...................................................................... 5

Satellite Symposia ...................................................................................... 8

Scientific Commitee .................................................................................. 11

Faculty ....................................................................................................... 12

General Information ................................................................................. 14

Contact ...................................................................................................... 16

Sponsors ................................................................................................... 17

List of Exhibitors ....................................................................................... 18

Exhibition Plan .......................................................................................... 19

Scientific Program

Thursday April 18, 2013 ........................................................................ 20

Friday April 19, 2013 ............................................................................. 52

Saturday April 20, 2013 ........................................................................ 78

Imprint ...................................................................................................... 90

3






Greetings

4

April 18 – 20, 2013






Dear colleagues,

The prognosis of patients with primary and secondary liver tumors has improved over the past decade due to refined surgical approaches, new systemic treatment options and irradiaton techniques and not last continous development and improvement of diagnotic tools. In addition to these well-established treatment modalities, there is an increasing use of interventional therapies directly targeting liver malignancies with curative and palliative intent.

The question “when and whom” to treat with an interventional treatment modality is again the focus of the 3rd ITLT which will take place in Essen, Germany and can only be answered within the framework of a close interdisciplinary cooperation.

During this conference a panel of internationally well renowned experts will outline the state of the art of different treatment modalities of liver malignancies such as hepatocellular and cholangiocellular carcinoma as well as liver metastases of other primaries. They will discuss the various treatment options and try to put them into a rationally based perspective.

We cordially invite you to attend this meeting and encourage you to participate actively by submitting an ab-stract focusing on multidisciplinary treatment or interventional oncology in liver malignancies considered for oral or poster presentation.

We are expecting an outstanding symposium and looking forward to meet you in Essen.

Prof. Dr. Hansjochen Wilke Chairman






Scientific Program Overview

09:00 Registration | Welcome and Introduction Lecture

10:00 Liver directed therapies: Are we changing prognosis? H. Wilke (Essen)

Keynote LecturesChair: M. Stahl (Essen) / W. Prevoo (Amsterdam)

10:20 Liver metastases: Is there a specific molecular signature? T. Seufferlein (Ulm)

10:40 Angiogenesis inhibition in cancer P. Carmeliet (Leuven)

11:00 Rationale of intraarterial therapies of liver malignancies J. F. Geschwind (Baltimore)

11:20 Does size matter in embolotherapy? F. Orsi (Milan)

11:40 Does size matter in local ablation? L. Crocetti (Pisa)

12:00 Imaging-follow-up after liver directed therapies: Which method, which response criteria? R. Lencioni (Pisa)

12:20 Special LectureCould modern radiotherapy cure liver malignancies J. Debus (Heidelberg)

13.00 Lunch Break

Lunch Symposia Nordion Inc.

Lunch Symposia Bayer Healthcare Deutschland / Bayer Consumer Care

Hepatocellular CarcinomaChair: J.-A. Koch (Essen) / J. Bruix (Barcelona)

14:10 Molecular signature of prognosis and outcomes in HCC J. Llovet (Barcelona / New York)

14:30 Transplantation in HCC: Which Patient, which criteria V. Mazzaferro (Milan)

14:50 Hepatocellular carcinoma downstaging to transplantation C. Toso (Geneva)

15:10 Resection or ablation H. Rhim (Seoul)

15:30 Intraarterial therapies: SIRT or TACE T. Jakobs (Munich)

15:50 Combination of liver directed therapies with systemic therapy J. Bruix (Barcelona)

16:10 Systemic therapy of HCC: State of the art 2013 R.T. Poon (Hong Kong)

16:30 Oral Presentation | Abstract Number 2Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept E. Garin (Rennes)

16:30 Oral Presentation | Abstract Number 4Initial Tumour Response after short and long interval chemo-embolization with drug-eluting beads (DC-Beads) in Hepato-cellular Carcinoma – a pilot study R. Syha (Tübingen)

Coffee Break

CholangiocarcinomaChair: M.K. Walz (Essen) / A. Vogel (Hannover)

17:10 Curative and palliative surgery H.Lang (Mainz)

17:30 Intraarterial therapies: SIRT or TACE? T. Helmberger (Munich)

17:50 Systemic therapies: State of the art 2013 A. Zhu (Boston)

18:10 Oral Presentation | Abstract Number 13Liver resection for cholangiocarcinoma: A single-center experience of the first decade of the new millennium A. Nickkholgh (Heidelberg)

18:16 Oral Presentation | Abstract Number 14Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocarcinoma: Optimal tolerance and prolonged overall survival R. Martin (Louisville)

18:30 Special LectureEndoscopic Treatment Options for Cholangiocarcinomas K. Mönkemüller (Birmingham)

5

Thursday April 18, 2013







6

Friday April 19, 2013

08.00 Breakfast Symposia Delcath Systems Inc.

Melanoma Chair: U. Keilholz (Berlin) / D. Schadendorf (Essen)

09:00 Four melanomas: Same name distinct diseases U. Keilholz (Berlin)

09:20 Palliative surgery in liver metastases from melanoma: Is there evidence?

R. Adam (Villejuif)

09:40 Intraarterial therapies: SIRT or TACE? P. Pereira (Heilbronn)

10:00 Modern systemic drug therapies in 2013 C. Garbe (Tübingen)

10:20 Oral Presentation | Abstract Number 15A Phase I Evaluation of Transcatheter arterial chemoembo-lization with doxorubicin-loaded LC beads (DEBDOX) in the treatment of liver metastases: A multicenter feasibility trial R. Martin (Louisville)

Coffee Break

Breast CancerChair: S. Kümmel (Essen) / C. Zielinski (Vienna)

11:00 Palliative surgery in liver metastases from breast cancer: Is there evidence?

M. Bergenfeldt (Lund)

11:20 Intraarterial therapies: SIRT or TACE? D. Coldwell (Louisville)

11:40 Modern systemic drug therapies in 2013 C. Zielinski (Vienna)

12:20 Special LectureIs there a role for interventional therapies in localized breast cancer S. Pfleiderer (Bremerhaven)

13.00 Lunch Break

Lunch Symposia Terumo Deutschland GmbH

Lunch Symposia Sirtex Medical Europe GmbH

GEPNETChair: K. Öberg (Uppsala) / A. Bockisch (Essen)

14:10 Diagnosis and treatment of GEPNET: The importance of pathology

A. Tannapfel (Bochum)

14:30 Surgery of liver metastasis from neuroendocrine tumors P. Goretzki (Neuss)

14:50 Intraarterial therapies: SIRT or TACE? T. de Baère (Villejuif)

15:10 Intraarterial therapies or surgery T. Pawlik (Baltimore)

15:30 Molecular imaging (Ga-68 SMS-Receptor PET/CT) and peptide receptor radionuclide therapy (PRRNT) of GEP-neuroendocrine neoplasms

R.P. Baum (Bad Berka)

15:50 Systemic therapy in 2013 K. Öberg (Uppsala)

Coffee Break

17:00–

18:00Poster Presentation

Pipeline Symposia Amgen Deutschland GmbH

Pipeline Symposia Lilly Deutschland GmbH







7

Saturday April 20, 2013

08.00 Breakfast Symposia PharmaCept GmbH / ART AG für regionale Tumortherapie e.V.

Colorectal Carcinoma Chair: H.-J. Meyer (Hannover) / P. Pereira (Heilbronn)

09:00 Resection of liver metastases G. Poston (Liverpool)

09:20 Resection or ablation W. Prevoo (Amsterdam)

09:40 Neoadjuvant treatment of liver metastases C.-H. Köhne (Oldenburg)

10:00 Portal vein embolization or radiation lobectomy R. Salem (Chicago)

10:20 HAI for the treatment of colorectal liver metastases N. Kemeny (New York)

Coffee Break

11:00 Combination of TACE with systemic therapies: Where are we now?

R. Martin (Louisville)

11:20 Combination of SIRT with systemic therapies: Where are we now?

H. Wasan (London)

11:40 Unresectable CRLM in 2013: For whom and when can interventional therapies be recommended in the light of modern drug therapies

D. Arnold (Hamburg)

12:00 Oral Presentation | Abstract Number 17Complete Response of liver metastases (LM) from colorectal cancer (CRC) after intra-arterial hepatic chemotherapy (IAHC) of floxuridine (FLO) : outcome and perspectives. G. Fiorentini (Pesaro)

12:18 Oral Presentation | Abstract Number 29Changes in VEGF-A-serum levels after chemoembolization with Irinotecan loaded drug-eluting beads (DEBIRI) in patients with chemorefractory liver metastases of colorectal cancer S. Pluntke (Essen)

12:20 Closing Remarks M. Anthuber (Augsburg)






Satellite Symposia


13:00 – 14:00 Lunch Symposia

Room Mailand Nordion Inc.

Clearly Targeted! Looking Beyond Systemic Therapies for the Treatment of Liver Cancer Chairman: S. Pluntke (Essen)

Targeted Liver Cancer Therapy in the Windy City. The Chicago Experience with TheraSphere®

R. Salem (Chicago)

The Future is Clear. The Milan Experience with TheraSphere® V. Mazzaferro (Milan)

The Lesson from Essen. Latest Insights on the Use of TheraSphere®

J. Schlaak (Essen)

Room New York Bayer Healthcare Deutschland / Bayer Consumer Care

Bayer Oncology – Today and Tomorrow Nexavar in HCC – from care to cure J. Bruix (Barcelona)

Therapeutic options in intermediate stage HCC: the Italian experience L. Bolondi (Bologna)

Stivarga-CORRECT Trial – CRC therapy A. Vogel (Hannover)


08:00 – 08:45 Breakfast Symposia

Room Mailand Delcath Systems Inc.

Evolution of Chemosaturation Therapy: A New Paradigm for Treating Whole Organ Liver Metastases Chairman: J. S. Zager (Florida)

Concentrated Chemotherapy to the Liver: The History of Chemosaturation J. S. Zager (Florida)

CHEMOSAT® Procedural Steps C. Engelke (Goettingen) Setting up a CHEMOSAT® Programme at your Hospital T. J. Vogl (Frankfurt)

8






Satellite Symposia


13:00 – 14:00 Lunch Symposia

Room Mailand Terumo Deutschland GmbH

Drug Eluting Beads – between the priorities of medical need and evidence Chairman: T. Helmberger (Munich)

DC Bead – some fundamental insights into product performance A. Lewis (Farnham)

Chemoembolization – on the way from empirical evidence towards approved standards D. Arnold (Freiburg)

Chemoembolization – from ultima ratio towards neoadjuvant concepts P.L. Pereira (Heilbronn)

Room New York Sirtex Medical Europe GmbH

SIR-Spheres microspheres – the proven and flexible SIRT Chairmen: D. Coldwell (Louisville) H. Wasan (London)

Introduction and welcome from the Chairs

The evidence for SIR-Spheres B. Sangro (Pamplona)

The flexibility of SIR-Spheres M. Pech (Magdeburg)

Surgery after SIR-Spheres M. Schön (Karlsruhe) Questions and Answers

17:00 – 18:00 Evening Symposia / Pipeline-Symposia

Europa Saal Chairman: H. Wilke (Essen)

Amgen Deutschland

Made by AMGEN – New drugs for Hematology/Oncology Targeting MET in gastric cancer M. Stahl (Essen)

Lilly Deutschland

New strategies targeting hepatocellular carcinoma M. Leschinger (Bad Homburg)

9






Satellite Symposia


08:00 – 08:45 Breakfast Symposia

Room Mailand PharmaCept GmbH / ART AG für regionale Tumortherapie e.V Chairman: J. Boese-Landgraf (Chemnitz)

Chemoembolization of liver tumors under the special focus of degradable starch microspheres. P. Bruners (Aachen)

ART-II study – Starch-TACE via surgical implanted arterial port systems U. Pohlen (Offenburg)

Oncolytic viruses for regional cancer therapy O. Ebert (Munich)

10






Scientific Commitee

11

Prof. Dirk ArnoldMedical Head of the Hubertus Wald Cancer CenterUniversity Cancer Center Hamburg (Germany)

Prof. Matthias AnthuberHead of Department of the General, Visceral and Transplantation Surgery DivisionKlinikum Augsburg (Germany)

Prof. Thierry de BaèreHead of the Department of Interventional RadiologyInstitut Gustave Roussy, Villejuif (France)

Prof. Andreas BockischDirector of the Clinic for Nuclear MedicineUniversity Hospital Essen (Germany)

PD Ullrich GraevenMedizinische Klinik IKliniken Maria Hilf GmbH/ Krankenhaus St. Franziskus, Mönchengladbach (Germany)

Prof. Nancy KemenyGastrointestinal Oncology ServiceMemorial Sloan Kettering Hospital New York (USA)

Prof. Jens-Albrecht KochDirector of the Department of Diagnostic and Interventional RadiologyKliniken Essen-Mitte (Germany)

Prof. Hauke LangDirector of the Clinic for General-, Visceral- and Transplantation SurgeryUniversity Hospital Johannes Gutenberg- Universität Mainz (Germany)

Prof. Riccardo LencioniDirector of the Division of Diagnostic Imaging and Intervention in the Department of Hepatology and Liver TransplantationUniversity Hospital of Pisa (Italy)

Prof. Robert C. G. MartinDirector of the Division of Surgical OncologyUniversity of Louisville (USA)

Prof. Hans-Joachim MeyerSecretary-General German Society for Surgery, Hannover (Germany)

PD Detlef MokaPrivate Practice for Nuclear Medicine, Essen (Germany)

Prof. Kjell ÖbergChairman Centre of Excellence Endocrine TumorsUniversity Hospital Uppsala (Sweden)

Prof. Philippe L. PereiraDirector of the Department of Radiology, Minimal-invasive Therapies and Nuclear medicineSLK-Kliniken Heilbronn GmbH (Germany)

Dr. Stefan PluntkeConsultant in Interventional OncologyKliniken Essen-Mitte (Germany)

Prof. Riad SalemDirector of Interventional Oncology in the Department of RadiologyNorthwestern University Chicago (USA)

Prof. Michael StahlDirector of the Department of Oncology, Hematology and Center of Palliative CareKliniken Essen-Mitte (Germany)

Dr. Harpreet S. WasanConsultant & Reader in (Medical) OncologyDepartment of Cancer MedicineHammersmith Hospital, London (United Kingdom)

Prof. Hansjochen WilkeDirector of the Department of Oncology, Hematology and Center of Palliative CareKliniken Essen-Mitte (Germany)






Faculty

12

Prof. René Adam Head of the Oncological Surgery Unit of the Hepatobiliary Center Paul Brousse Hospital, Villejuif (France)

Prof. Dirk ArnoldDirector of the Clinic for Medical OncologyTumor Biology Center Freiburg (Germany)

Prof. Matthias AnthuberHead of Department of the General, Visceral and Transplantation Surgery DivisionKlinikum Augsburg (Germany)

Prof. Thierry de BaèreHead of the Department of Interventional RadiologyInstitut Gustave Roussy, Villejuif (France)

Prof. Richard P. BaumHead of Department for Molecular RadiotherapyENETS Center of ExcellenceZentralklinik Bad Berka (Germany)

Prof. Magnus BergenfeldtDepartment of SurgerySkåne University Hospital, Lund (Sweden)


Prof. Jordi BruixHead of BCLC groupHospital Clinic University of Barcelona (Spain)

Prof. Peter CarmelietDirector Vesalius Research Center (VRC)Katholieke Universiteit Leuven (Belgium)

Prof. Douglas M. ColdwellDirector of the Department Vascular and Interventional RadiologyUniversity of Louisville (USA)

Prof. Laura CrocettiDivision of Diagnostic Imaging and Intervention in the Department of Hepatology and Liver Transplantation University Hospital of Pisa (Italy)

Prof. Jürgen DebusProfessor and Chairman Department Radiation OncologyUniversity Hospital Heidelberg (Germany)

Prof. Claus GarbeHead of the Section of Dermatologic OncologyUniversity Hospital Tübingen (Germany)

Prof. Jean François GeschwindDirector of the Interventional Radiology CenterJohns Hopkins University School of Medicine, Baltimore (USA)

Prof. Peter GoretzkiHead of the Department of SurgeryStädt. Kliniken Neuss Lukas Krankenhaus GmbH (Germany)

Prof. Dr. Thomas HelmbergerDirector of the Department of Radiology, Interventional Radiology, Neuroradiology and Nuclear medicineKlinikum Bogenhausen, Munich (Germany)

PD Tobias F. JakobsHead of the Department of RadiologyHospital Brothers of Charity, Munich (Germany)

Prof. Ulrich KeilholzDeputy Director of the Charité Comprehensive Cancer CenterCharité, Berlin (Germany)

Prof. Nancy KemenyGastrointestinal Oncology ServiceMemorial Sloan Kettering Hospital New York (USA)


Prof. Claus-Henning KöhneHead of Department of the Department of Oncology and HematologyKlinikum Oldenburg gGmbH, Oldenburg (Germany)

PD Sherko KümmelDirector of the Department of SenologyKliniken Essen-Mitte (Germany)

Prof. Hauke LangDirector of the Clinic for General-, Visceral- and Transplantation SurgeryUniversity Hospital Johannes Gutenberg-Universität Mainz (Germany)

Prof. Riccardo LencioniDirector of the Division of Diagnostic Imaging and Intervention in the Department of Hepatology and Liver TransplantationUniversity Hospital of Pisa (Italy)

Prof. Josep M LlovetProfessor of Research BCLC Group, Liver UnitHospital Clínic Barcelona (Spain)Director of the HCC Research Program Professor of Medicine Mount Sinai School of Medicine New York (USA)

Prof. Vincenzo MazzaferroG.I. Surgery and Liver Transplant UnitNational Cancer Institute Milan (Italy)






Faculty

13

Prof. Klaus MönkemüllerDepartment of Medicine, Division of Gastroenterology and HepatologyUniversity of Alabama, Birmingham (USA)

Prof. Robert C. G. MartinDirector of the Division of Surgical OncologyUniversity of Louisville (USA)

Prof. Hans-Joachim MeyerSecretary-General German Society for Surgery, Hannover (Germany)

Prof. Kjell ÖbergChairman Centre of Excellence Endocrine TumorsUniversity Hospital Uppsala (Sweden)

Prof. Franco OrsiDirector Unit of Interventional RadiologyIEO IstitutoEuropeo di Oncologia Milan (Italy)

Prof. Timothy PawlikDirector of the Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary ClinicJohns Hopkins Hospital, Baltimore (USA)

Prof. Philippe L. PereiraDirector of the Department of Radiology, Minimal-invasive Therapies and Nuclear medicineSLK-Kliniken Heilbronn GmbH (Germany)

PD Stefan PfleidererHead of the Department of Radiology, Interventional Radiology, Neuroradiology and Nuclear medicineKlinikum Bremerhaven-Reinkenheide (Germany)

Prof. Ronnie PoonSuen Chi-Sun Professor of SurgeryChair Professor of Hepatobiliary and Pancreatic SurgeryThe University of Hong Kong (China)

Prof. Graeme PostonDepartment of Liver SurgeryAnintree University Hospitals Liverpool (United Kingdom)

Dr. Warner PrevooDepartment of RadiologyHet Nederlands Kanker Instituut Amsterdam (Netherlands)

Dr. Stefan PluntkeConsultant in Interventional OncologyKliniken Essen-Mitte (Germany)

Prof. Hyunchul RhimDepartment of Radiology Samsung Medical Center, SungkyunkwanUniversity Seoul (Korea)

Prof. Riad SalemDirector of Interventional Oncology in the Department of RadiologyNorthwestern University Chicago (USA)

Prof. Dirk SchadendorfDirector of the Clinic for DermatologyUniversity Hospital Essen (Germany)

Prof. Thomas SeufferleinDirector of Department of Internal Medicine I University Hospital Ulm (Germany)

Prof. Michael StahlDirector of the Department of Oncology, Hematology and Center of Palliative CareKliniken Essen-Mitte (Germany)

Prof. Andrea TannapfelDirector of the Institute of Pathology Ruhr-University Hospital, Bochum (Germany)

Prof. Christian Toso Department of Visceral Surgery and Transplantation University Hospital of Geneva (Switzerland)

Prof. Arndt Vogel MHH - Hannover Medical School (Germany)

Prof. Martin K. WalzDirector of Department of Surgery and Centre of Minimally Invasive SurgeryKliniken Essen-Mitte (Germany)

Dr. Harpreet S. WasanConsultant & Reader in (Medical) OncologyDepartment of Cancer MedicineHammersmith Hospital, London (United Kingdom)

Prof. Hansjochen WilkeDirector of the Department of Oncology, Hematol-ogy and Center of Palliative CareKliniken Essen-Mitte (Germany)

Prof. Christoph C. Zielinski Director, Clinical Division of Oncology and Depart-ment of Medicine ICoordinator, Comprehensive Cancer CenterMedical University Vienna (Austria)

Prof. Andrew X. ZhuDirector, Liver Cancer ResearchMassachusetts General Hospital Cancer CenterHarvard Medical School, Boston (USA)






General Information

14

Venue

Messe Essen GmbHCongress Center WestNorbertstrasse45131 Essen, GermanyWebsite: www.cc-essen.de

Registration Fees Registration Day Ticket* Day Ticket* Day Ticket* Fees* Thursday Friday Saturday

April 18 - 20 300,00 EUR 150,00 EUR 150,00 EUR 100,00 EUR

ESMO-Member 225,00 EUR 110,00 EUR 110,00 EUR 75,00 EUR

ESSO-Member 225,00 EUR 110,00 EUR 110,00 EUR 75,00 EUR

Poster Presenter / Abstract Author 150,00 EUR

MRTA / Nursing Staff 150,00 EUR 60,00 EUR 60,00 EUR 30,00 EUR

Student 150,00 EUR 60,00 EUR 60,00 EUR 30,00 EUR

*The registration fees are stated including 19% German VAT.

©M

ESSE

ESS

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mbH






General Information

15

CME CreditsWe are pleased to inform you that the 3rd ITLT will offer Continuing Medical Education (CME) for participating in the 3rd ITLT Congress in Essen 2013!

THE 3rd ITLT CME committee has successfully applied to:

Nordrheinische Akademie für ärztliche Fort- und Weiterbildung with 20 points, category A(18 April: 8 points / 19 April: 8 points / 20 April 4 points)

AIO Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.V. with 15 AIO Points (18 April: 7 AIO-P. / 19 April: 5 AIO-P. / 20 April 2 AIO-P.)

European Accreditation Council for Continuing Medical Education (EACCME) with 13 European CME credits (ECMEC):(18 April: 5 credits / 19 April: 5 credits / 20 April: 3 credits)

European Society for Medical Oncology (ESMO) with 17 ESMO-MORA cat. 1: (18 April: 8 ESMO-MORA cat. 1 / 19 April: 6 ESMO-MORA cat. 1 / 20 April: 3 ESMO-MORA cat. 1)

Akademie für Fort- und Weiterbildung in der Radiologie with 20 points, cat. CME-1

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For further information please call us at: +49 2161 - 4642 102 or visit us under: www.mlm-labs.com






Contact

16

Organizing Committee / Scientific Host

Coordination Scientific ContentDr. Stefan PluntkeConsultant in Interventional OncologyKliniken Essen-Mitte (Germany)E-Mail: [email protected]

Under the auspices of

OrganizerSAVC GmbHServicegesellschaft fürAllgemein- & Viszeralchirurgie Langenbeck-Virchow-Haus 10117 Berlin, Germany

Organizing SectretariatINTERPLANCongress, Meeting & Eventmanagement AGLandsberger Str. 15580687 Munich, Germany

Project ManagementTanja Lypp Tel.: +49 (0)89 54 82 34-17Fax: +49 (0)89 54 82 34-43E-Mail: [email protected]

Prof. Hansjochen WilkeDirector of the Department of Oncology, Hematology and Center of Palliative CareKliniken Essen-Mitte (Germany)


Prof. Philippe L. PereiraDirector of the Department Klinik of Radiology, Minimal-invasive Therapies and Nuclear MedicineSLK-Kliniken Heilbronn GmbH (Germany)


Prof. Hauke LangDirector of the Clinic for General-, Visceral- and Transplantation SurgeryUniversity Hospital Johannes Gutenberg- Universität Mainz (Germany)

In cooperation with the Academy for Continuing Medical Education in Radiology

CAO-V Chirurgische Arbeitsgemeinschaft für Onkologie






Sponsors

17

FSA-List (Status at the time of printing)

According to the principles of the FSA-Kodex, please find here a full list of the financial involvement of FSA-Members.

Amgen GmbH Exhibition Space 6 qm 2.190,00 EUR Sponsor of Pipeline Symposium 2.500,00 EUR

Bayer Healthcare Deutschland Exhibition Space 9 qm 3.285,00 EUR Sponsor of Lunchsymposium 6.000,00 EUR

Baxter Exhibition Space 6 qm 2.190,00 EUR

Eisai GmbH Exhibition Space 4 qm 1.460,00 EUR

IPSEN PHARMA Exhibition Space 6 qm 2.190,00 EUR

Lilly Deutschland GmbH Sponsor of the Congress 2.500,00 EUR

MERCK SERONO GmbH Exhibition Space 6 qm 2.190,00 EUR

Novartis Deutschland GmbH Exhibition Space 8 qm 2.920,00 EUR

Pfizer Pharma GmbH Sponsor of the Congress 1.000,00 EUR

Roche Pharma AG Exhibition Space 11 qm 4.042,50 EUR Sponsor of the lanyards 2.000,00 EUR

ART Arbeitsgemeinschaft

für Regionale Tumortherapie






List of Exhibitors

Name Stand No.

amedo smart tracking solutions GmbH F.07

Amgen GmbH F.20

angiopro GmbH F.27

Baxter F.25

Bayer Healthcare Deutschland F.21

biolitec biomedical technology GmbH F.14

BOH - Begehbare Organe & Health GmbH E.01

Boston Scientific Medizintechnik GmbH F.24

CeloNova BioSciences Inc. F.16

Covidien F.31

Delcath Systems Limited F.01

Dr. Falk Pharma GmbH F.26

Eisai GmbH F.29

Fresenius Kabi Deutschland GmbH F.11

HEXAL AG F.05

IPSEN PHARMA F.19

M+C Vertriebs-GmbH F.17

Medtronic GmbH F.13

MERCK SERONO GmbH F.12

Merit Medical GmbH F.06

MeVis Medical Solutions AG F.30

Nicolai GmbH F.10

Nordion F.22

Novartis Deutschland GmbH F.15

Pfizer Pharma GmbH F.28

PharmaCept GmbH F.08

Roche Pharma AG, Grenzach-Wyhlen F.18

Sanofi-Aventis Deutschland GmbH F.32

Sirtex Medical Europe F.09

Takeda Pharma Vertrieb GmbH & Co. KG F.23

Terumo Deutschland GmbH F.04

TEVA GmbH F.33

Vital, A Toshiba Medical Systems Group Company F.02

18

(Status at the time of printing)






Exhibition Plan

19

1stFloor

Entrance

toFoyer

PlenaryHallEuropa

Registrationatgroundfloor

Entrance

Entrance

Catering

Elevator

Stairs

FreeAir

Stairs

from

Ground

Level

Catering

Catering

F.01

F.03

F.05

F.09

F.10

F.06

F.07

F.08

F.11

F.21

F.22

F.20

F.19

F.12

F.14

F.18

F.13

F.15

F.16

F.17

Catering

Registrationat

GroundFloor

subjecttoalterations!

status:March2013/sar

F.04

F.24

F.23

2m3m

3m

3m 3m

2,2m

5m 4m 4m 4m

2m

1m

2m

3m 3m

3m

3m

3m

2m

2m

2m

3m

3m

3m

3m

3m

3m

3m 3m

7m

3m 3m 3m

2m

3m

1m

3m

6m

3m

2m

F.27

F.26

F.25

F.30

F.28

F.31

4m

F.29

2m

F.32

F.33

F.02






Scientific Program

20


10:00 – 10:20 Liver directed therapies: Are we changing prognosis?

Prof. Hansjochen Wilke

Director of the Department of Oncology, Hematology and Center of Palliative CareKliniken Essen-Mitte (Germany)

As a part of the interdisciplinary management of malignant liver tumors and liver metas-tases of extrahepatic primaries, transarterial delivered treatment modalities have gained increasing interest over the past decade. This is in part due to the development of new tech-nical devices, embolization techniques and materials. Currently applied liver directed thera-pies include classical chemoperfusion, chemoembolisation, radioembolisation and bland embolization.

Meanwhile there is growing evidence for efficiency of liver directed therapies in liver tumors of various entities, with the most prominent ones being hepatocellular carcinoma, colorectal cancer, and neuroendocrine tumors. There is also growing evidence that these therapies may be beneficial for other tumor entities such as malignant melanoma and breast cancer. Clinical trials investigating the potential value of liver directed therapies have generated en-couraging results in terms of response, survival and quality of life in different tumor entities and in clinical situations ranging from first-line to last-line treatments. The answer to the question “Do liver directed therapies really change the prognosis of patients with malignancies of the liver” is “Yes we can, at least for individual patients”. However, we also clearly need larger and especially randomized trials addressing the question for whom or when (first or subsequent lines) or how (i.e. interventional therapies alone, in combination with systemic treatment or prior to surgical approaches) liver directed should/can be used. This will help us to recommend liver directed treatments as more evidence based treatment options as currently possible.

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10:20 – 10:40 Liver metastases of colorectal cancer: Is there a specific molecular signature?

Prof. Thomas T. W. Seufferlein

Director of Department of Internal Medicine I University Hospital Ulm (Germany)

Over the past years many efforts have been taken to unravel potential differences in the molecular and cellular biology of liver metastases as compared to the primary tumors. These efforts shall improve our understanding of carcinogenesis, tumor evolution and the principle of metasta-sis and therefore give us novel clues and targets to prevent metastases and treat colorectal cancer.Many studies have been undertaken using gene expression analyses based on cDNA arrays of primary tumors and metastases. Interestingly, there is comparatively little overlap between the different published signatures. There are technical and methodological reasons to explain this finding. One reason may also be the fact that many of these studies were undertaken using unrelated primary tumors and metastases of colorectal cancer. Because of a certain molecular heterogeneity between primary tumors, this approach is prone to yield false positive differences between the primary tumor and the metastases unless the sample size examined is high. The latter is not the case in the majority of the published studies. Nevertheless, one gene has consistently been found to be overexpressed in metastases of colorectal cancer as compared to primary tumors, Secreted Phosphoprotein 1 (SPP1/Osteopontin; Shibayama, 2011).A more targeted approach has been taken by Vakiani and coworkers (Vakiani et al., 2012) who examined core mutations in primary colorectal cancers and matching metastases including mu-tations in K-ras, B-raf, PI3-kinase and p53. The major finding of their study using both, frozen samples and FFPE samples, is that there is a more than 90% concor-dance in the mutation profile of the primary tumor and its respective metastasis. There was also a high concordance in the mutation profile between different metastases.A different approach has been taken by a group using high resolution array CGH and expression profiling to examine primary tumors and matched metastases (Stange et al., 2010). The authors found that chromosomal aberrations and gene expression profiles are surprisingly similar in primary tumors and matched metastases. The group detected only 11 aberrations per patient tumor that were different between the primary tumor and metastases. They found in total 16 genes that were statistically significantly differentially expressed between primary tumor and metastases, less than 0.01% of all genes. Given the high concordance in the molecular profile between primary tumor and its metastasis the authors concluded that at least in colorectal cancer, an effective dissemination of tumor cells occurs rather late in the molecular develop-ment of colorectal cancer. The alternative explanation, a parallel, independent development of such similar genomic profiles appears rather unlikely. The group also described a gain in the chromosomal band 11p15.5 in about a third of the liver metastases and identified two genes, ASCL2 and IGF2, as potential driver genes of this gain. Overexpression of these two genes could shift the relation between differentiation and self renewal within a metastasis and therefore affect the clinical behavior of the metastases. The data described so far used different qualities of tumor material (fresh frozen vs. paraffin embedded tissues). So far little attention has been paid to the different areas within a tumor. A recent paper examined different areas of a renal cell carcinoma and its metastases (Gerlinger et al., 2012). Using multiregion sequencing the authors detected su bstantial intratumoral hetero-geneity for multiple tumor-suppressor genes. They also detected gene expression signatures of good and poor prognosis in different regions of the same tumor. Corresponding data in colorectal cancer are as yet not available, but it is fair to assume that also colorectal cancers at least to some degree also exhibit intratumoral heterogeneity. This adds another level of complexity when we in-terpret gene expression profiles that have been obtained from single tumor biopsies, in particular when we want to use these signatures to personalize a patients cancer treatment. Finally, we have to consider that the selection pressure exerted on a primary tumor or its metastases by chemotherapy combinations or targeted therapies may be even more relevant than molecular differences between the primary tumor and the metastases. Recent data show that during treatment of patients with K-ras wild type CRC using anti-EGFR antibodies the amount of K-ras mutant DNA detectable in the patients blood substantially increases most likely due to increased proliferation of K-ras mutated, anti-EGFR resistant tumor cell clones that were present already at the beginning of the treatment albeit at low frequency (Diaz et al., 2012).






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KEYNOTE LECTURES Chair: M. Stahl (Essen) / W. Prevoo (Amsterdam)

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Conclusions:• Coremutationsaswellaschromosomalaberrationsandgeneexpressionprofilesare surprisingly similar in CRC primary tumors and matched metastases.• Effective dissemination of tumor cells appears to occur rather late in the molecular development of colorectal cancer.• Metastasesmaygainastemcellsignatureandchangetheirbehaviour.• Noveldataalsosuggestsubstantialintratumoralheterogeneitythatwillaffectthebehaviour of tumors and their metastases.• Wehavesofarfewmoleculardataontumorevolutionduringdrugtherapy,butitcertainly exists and is relevant.

References:Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers.Nature. 2012 Jun 28;486(7404):537-40. doi: 10.1038/nature11219.Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. Intra- tumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012 Mar 8;366(10):883-92. doi: 10.1056/NEJMoa1113205. Erratum in: N Engl J Med. 2012 Sep Shibayama M, Maak M, Nitsche U , Gotoh K, Rosenberg R, Janssen KP Prediction of Metas-tasis and Recurrence in Colorectal Cancer Based on Gene Expression Analysis: Ready for the Clinic? Cancers 2011, 3(3), 2858-2869; doi:10.3390/cancers3032858Stange DE, Engel F, Longerich T, Koo BK, Koch M, Delhomme N, Aigner M, Toedt G, Schirmacher P, Lichter P, Weitz J, Radlwimmer B. Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain.Gut. 2010 Sep;59(9):1236-44. doi: 10.1136/gut.2009.195701. Epub 2010 May 17.Vakiani E, Janakiraman M, Shen R, Sinha R, Zeng Z, Shia J, Cercek A, Kemeny N, D’Angelica M, Viale A, Heguy A, Paty P, Chan TA, Saltz LB, Weiser M, Solit DB. Comparative genomic analy-sis of primary versus metastatic colorectal carcinomas.J Clin Oncol. 2012 Aug 20;30(24):2956-62. doi: 10.1200/JCO.2011.38.2994. Epub 2012 Jun 4.






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10:40 – 11:00 Angiogenesis inhibition in cancer

Prof. Peter Carmeliet

Director Vesalius Research Center (VRC)Katholieke Universiteit Leuven (Belgium)

Angiogenesis, the growth of new blood vessels, plays a crucial role in numerous diseases, including cancer. Anti-angiogenesis therapies have been developed to deprive the tumor of nutrients. Clinically approved anti-angiogenic drugs offered prolonged survival to numerous cancer patients. However, the success of anti-angiogenic VEGF-targeted therapy is limited in certain cases by intrinsic refractoriness and acquired resistance. New strategies are needed to block tumor angiogenesis via alternative mechanisms. We are therefore exploring whether targeting endothelial metabolism can be a possible alternative therapeutic strategy for anti-angiogenic therapy.


11:00 – 11:20 Rationale of intraarterial therapies of liver malignancies

Prof. Jean-Francois H. Geschwind

Professor Radiology, Surgery and OncologyDirector of the Interventional Radiology CenterJohns Hopkins University School of Medicine, Baltimore (USA)

The rationale for regional chemotherapy is to maximize drug concentrations and tumor drug uptake in the target organ and minimize systemic toxicity. For regional drug delivery to success-fully impact relevant outcomes, several important principles regarding tumor biology, drug pharmacology and delivery systems must be fulfilled. Liver cancer, either primary or secondary from colorectal cancer, complies with these principles, as liver cancer has a regional pattern of dissemination (with the liver being the only site of metastatic disease for long periods of time in some cases) that supports a loco-regional approach. Other salient features include the selective blood supply of liver cancer by the hepatic artery and availability of active drugs with suitable pharmacokinetic properties.

The ultimate goal of regional therapy is to improve the therapeutic index by increasing efficacy and decreasing systemic toxicity. Hepatic arterial therapy relies on two important assump-tions: Regional delivery of the drug leads to increased local concentration and therefore in-creased therapeutic response and regional delivery of the drug leads to decreased systemic exposure and reduced systemic toxicity. The suitability of any specific drug for regional therapy can be evaluated by the extent to which it fulfills these assumptions.

However, drugs that must be activated at a site other than the arterial infusion site have no regional delivery advantage. It should be noted that although pharmacokinetic parameters may allow a selective increase in hepatic tumor exposure, the crucial target effect of a particular drug (e.g. DNA incorporation of a thymidine analog) might also exhibit non-linear kinetics. In this case, the impact on what actually is most important, the drug effect, rather than the increased drug concentration, might be less selective at high rather than at low dose rates. This is the concept of tissue-related pharmacokinetics and takes into account not only saturating pharmacokinetics in the tumor but also in systemic tissues. If at high dose rates, the plateau for the effect is higher in systemic tissues rather than for the tumor itself, loss of regional selectivity is observed.






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The paradigm that increased dose will result in increased biologic effect has been challenged by the recent development of targeted agents active against cancer. Most cytotoxic drugs act on DNA or tubulin, exhibit a sigmoidal steep dose-response curve and dose selection is based on maximal tolerated dose. However, for targeted therapies, more is not necessarily better. Pharmacodynamic effect is thought to be the result of receptor occupancy and saturation. Optimal target inhibition occurs at a specific drug concentration, and increasing the dose will not increase the effect. Furthermore, at useful drug concentrations, the maximum tolerated dose may have not been reached. As this has been recognized, the need for new strategies to define the clinically active dose level for this kind of drugs is evident. The traditional phase I trial, useful for cytotoxic drugs dose selection, does not accomplish the goal for targeted agents. Other parameters including pharmacokinetic endpoints such as achieving a pre-defined target plasma level or direct measurement of target inhibition may be more relevant.

As the field of interventional radiology continues to evolve, the notion of how intraarterial-based procedures impact the tumor microenvironment will become increasingly important and relevant. As a result, the knowledge of how drugs can be better delivered to tumor tissue will be even more critical in order to improve tumor response and more importantly patient survival.

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11:20 – 11:40 Does size matter in embolotherapy?

Prof. Franco Orsi

Director Unit of Interventional RadiologyIEO IstitutoEuropeo di Oncologia Milan (Italy)

Although liver resection remains the gold-standard curative local treatment, during the past three decades, several local treatments have been developed, such as intraarterial treatments, percutaneous thermal ablation, stereotactic radiotherapy and, more recently, high intensity focused ultrasound. The intra-arterial route for tumor liver therapy is based on the premise that hepatic tumors are fed mainly, if not exclusively, by arteries. Based upon this theory, investigators proposed different local treatments for liver tumors, such as chemoembolization (TACE), bland embolization (TAE), intra-arterial chemotherapy (HIAC) and more recently the so called “radio-embolization” (SIRT). TACE and TAE, however, represent the most common endovascular approaches for local treatment of liver tumors, for which were developed many different embolic agents.

Gelfoam sponge powder was used as one of the first embolic agents, but the efficacy was reported to be low because it stayed only temporarily within the tumor vascular mesh. Polyvinyl-alcoholic foam (PVA) is another embolic agent often used for liver tumor; it has been reported too heterogeneous in shape and size. The embolizing performance of this material can be very unpredictable, mainly because the particles clump and aggregate within the vessel lumen (and very often, to the catheter) and cause occlusion of larger and too peripheral vessels. It may allow for the development of new distal feeding arteries to the target lesion, with poor clinical outcomeIn the past two decades several different spherical embolic agents have been then intensively investigated, such as trisacryl gelatin microspheres, collagen-coated microspheres, dextran microspheres and PVA spheres. The development or refinement of spherical embolic particles has remarkably in-creased the spectrum of interventional radiology, especially in the treatments of HCC or the so called “hypervascular” liver lesions, reducing or avoiding particle clusters with-in peripheral vessels and allowing for a deeper penetration in the neoplasm vasculature, with permanent and effective staining. Up to now, several new different embolic agents were developed, some of them with promising new features, such as drug elution.

According to the literature, microsphere calibration should allow for adapting the micro-spheres to the size of the vessels to be occluded, so that accurate targeting can be obtained. Moreover, the use of calibrated microspheres should permit a better control of the extent of occlusion, which depends on the number of injected particles and the penetration of the embolic agent within the tissue.Until now, there has been no evidence to determine the most important feature an embolic agent should have for effective local treatment. The dimension and shape of embolic particles, however, seem to be the most important characteristics for this aim.

In the majority of published studies on HCC treatment with TAE, the reported embolic agent is gelatine sponge, which may induce only temporarily ischemia and without distal tumor vessel embolization. Only recently, few new studies on new embolic agents, such as resin or gela-tine microspheres, are available. Even if there is no evidence for a better survival benefit from DEB TACE than TACE and also TAE, if performed with small particles (40/100micron), there is an increasing general consensus about the need to use the smallest available particles in treating HCC, in order to achieve a better, durable and deeper embolic effect, independently by the use of drug or not. Few papers on HCC treatment with TAE, using very small particles, reported an interesting safety profile with local results comparable with DEBTACE/TACE series(33). However, based on data coming from old papers on TAE with gelatin sponge, BCLC doesn’t recommend the use of TAE for HCC.






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11:40 – 12:00 Does size matter in ablation?

Prof. Laura Crocetti, MD, PhD, EBIR

Division of Diagnostic Imaging and Intervention in the Department of Hepatology and Liver Transplantation University Hospital of Pisa (Italy)

Loco-regional treatments play a key role in the management of primary and liver tumors. Due to the inner features of all ablative modalities, related to the type of energy and the design of the de-vices, the size of tumor represents one of the most important factors to be taken into consideration in order to guarantee the highest probability of treatment success. Hepatocellular carcinoma (HCC) represents a unique example on how different interventional techniques – ablative and intrarterial – can be used and combined according to tumor size, number and location. In very early stage HCC the presence of a solitary small nodule, less than <2cm in diameter, in Child-Pugh A patients, the absence of microvascular invasion and dissemination offers the highest likelihood of cure. Nodules <2cm, that are not not subcapsular nor perivascular, are the ideal target for percutaneous RFA, which is considered the standard technique for liver tumor ablation at most institutions . In patients with very early HCC the complete response rate approaches 97%, with 5 year survival rates of 68% . It has also been pointed out as individual components belonging to each patient (e.g. whether the tumor is central or peripheral, close or distant form bile ducts, in patient who is lean or overweight, presenting with or without portal hypertension, etc.) influence the results of each treatment making it better or worse than average. Since clinical experience suggests that treatment by RFA of HCC tumors in subcapsular location or adjacent to the gallbladder is associated with an increased risk of major complications and incomplete ablation, such tumor locations are considered favourable for hepatic resection. Therefore, in patients with very early HCC, RFA can be offered as a first-line treatment, considering surgical approach when individual variables, including tumor location, would make RFA not feasible or not safe. Patients with early stage disease have preserved liver function (Child–Pugh A and B) with solitary HCC or up to 3 nodules <3 cm in size. These patients can be effectively treated by resection, liver transplantation or percutaneous ablation with possibility of long term cure, and 5-year survival figures ranging from 50% to 75%. Among different ablative techniques, RFA is currently considered as the best treatment options in patients with early stage HCC. Five randomized controlled trials (RCTs) have compared RFA versus PEI for the treatment of early-stage HCC. These investigations consistently showed that RFA is more effective than PEI, leading to a better local control of the disease. The assessment of the impact of RFA on survival has been more controversial. While a survival benefit was identified in the three RCTs performed in Asia, the two European RCTs failed to show statistically significant differences in overall survival between patients who received RFA and those treated with PEI, despite the trend favoring RFA. Nevertheless, three independent meta-analyses including all RCTs, have confirmed that treatment with RFA offers a survival benefit as compared with PEI, particularly for tumors larger than 2 cm, thus establishing RFA as the standard percutaneous technique in these patients. Recent reports on long-term outcomes of RFA-treated patients have shown that in patients with Child-Pugh class A and early-stage HCC, 5-year survival rates are as high as 51-64%, and may reach 76% in patients who meet the BCLC criteria for surgi-cal resection . An important factor that affects the success of RFA is the ability to ablate all viable tumor tissue and create an adequate tumor-free margin. The target tumor should not exceed 3 cm at its longest axis to achieve best rates of complete ablation using most of the currently available devices. More-over, even in small tumors, the ability of RFA to achieve complete tumor eradication appears to be dependent on tumor location. Histological studies performed in liver specimens of patients who underwent RFA as bridge treatment to transplantation showed that the presence of large (3 mm or more) abutting vessels result in about 50% drop in the rate of complete tumor necrosis because of the heat loss due to perfusion-mediated tissue cooling within the area to be ablated. Therefore in patients with solitary HCC >3cm and <5cm in size the success rate of RFA alone is decreased; combination with intra-arterial treatment could be considered in these patients. A combination of TACE followed by RFA has been used to minimize heat loss due to perfusion-mediated tissue cool-ing and increase the therapeutic effect of RFA. Recently the results of a RCT aimed to evaluating the therapeutic efficacy of combining RFA with TACE for treating intermediate-sized (3.1-5 cm) HCCs have been published. Local tumor progression rate were significantly lower in the TACE-RFA treated group with respect to the RF only group (6% versus 39%, p= 0.012) . Under a different per-spective, TACE with drug-eluting beads has been performed after an RFA procedure to increase tumor necrosis by exposing to high drug concentration the peripheral part of the tumor, where






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only sub-lethal temperatures may be achieved in a standard RFA treatment. Further research to determine optimal methods of combining chemotherapeutic regimens (both agent and route of administration) with RFA is needed. Patients with solitary large tumors (exceeding 5 cm in size) deserve a special mention. Even if these patients cannot be considered in an early stage because they do not qualify for transplantation, no upper limit of size for surgical resection appears in the BCLC flowchart, and these patients should not escape surgical referral because their tumors are too large. Different ablative modalities are not currently providing sufficient volume of ablation to treat successfully these tumors and the results of trans-arterial therapies as stand-alone treat-ment are highly variable in this clinical scenario. Moreover, when tumor size is above 5 cm the advantages of combination therapies seem negligible. On the other hand, it has been suggested that patients with large solitary tumors may benefit from surgery because surgical mortality has decreased and because patients with operable solitary large tumors may be a self-selected group with low tendency for multifocal disease. Microwave ablation (MWA) is emerging as a valuable alternative to RFA for thermal ablation of HCC. Electro-magnetic microwaves heat matter by agitating water molecules in the surrounding tissue, producing friction and heat, thus inducing cellular death via coagulation necrosis . The main features of MW technology, when compared with existing thermoablative technologies, include consistently higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times, and an improved convection profile. As a result, the advantage of MWA over RFA is that treatment outcome is less affected by vessels located in the proximity of the tumor. In addition, because MW ablation does not rely on an electrical circuit as does RF ablation, multiple applicators can be applied simultaneously. So far, only one RCT has compared the effectiveness of MWA with that of RFA . Although no statistically significant differences were observed with respect to the efficacy of the two procedures, a tendency favoring RFA was recognized in that study with respect to local recurrences and complications rates. It has to be pointed out, however, that MWA technology has evolved significantly since the publication of this trial. Recent advances in MW engineering have allowed the design of new MW systems with the potential for larger, more controlled ablation zones. A new, non-chemical non-thermal image-guided ablation techniques that is currently undergoing clinical investigation in early stage HCC is irreversible electroporation (IRE). IRE is a method to induce irreversible disruption of cell membrane integrity, by changing the transmembrane potential, resulting in cell death with-out the need for additional pharmacological injury. IRE creates a sharp boundary between the treated and untreated area in vivo. This would suggest that IRE has the ability to sharply delineate the treatment area from the non-treated, and that treatment planning can be precisely performed according to mathematical predic-tions. Moreover, because IRE is a non-thermal technique, there appears to be complete ablation to the margin of blood vessels without compromising the functionality of the blood vessels. Therefore, issues associated with perfusion-mediated tissue cooling or heating (a significant challenge with thermal methods) are not relevant. So far, however, the published data of the technique concern studies conducted in pre-clinical models and the results of the on-going prospective clinical trials are strongly demanded. References1. Crocetti L, de Baere T, Lencioni R. Quality improvement guidelines for radiofrequency ablation of liver tumours. Cardiovasc Intervent Radiol 2010;33(1):11-17. 2. Lencioni R, Crocetti L. Local-regional treatment of hepatocellular carcinoma. Radiology 2012; 262(1):43-58. 3. European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56(4):908-943.






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12:00 – 12:20 Imaging-follow-up after liver directed therapies: Which method, which response criteria?

Prof. Riccardo Lencioni

Director of the Division of Diagnostic Imaging and Intervention in the Department of Hepatology and Liver TransplantationUniversity Hospital of Pisa (Italy)

The development of imaging criteria for response assessment after liver-directed therapies has been a long process. In 2000, the European Association for Study of Liver (EASL) first proposed an amendment to the WHO criteria, the ones most commonly used by investigators around the globe at that time, for the assessment of tumor response in hepatocellular carcinoma (HCC). The EASL guideline recommended to take into account treatment-induced tumor necrosis and to measure the product of the longest diameters of the viable portion of the tumor, as recognized by contrast-enhanced radiological imaging, instead of the product of the longest diameters of the whole tumor mass. A limitation of the EASL guideline is that it only provides recommendations for the assessment of target lesions. With the advent of systemic treatments for HCC, the need for a comprehensive model for response assessment has been widely acknowledged. In the meantime, the WHO criteria were largely replaced by the RECIST criteria in oncology trials. The introduction of RECIST has been a major advance-ment in the standardization of response assessment. However, the RECIST guideline, similar to the WHO criteria, is based on the concept of tumor shrinkage as the only measure of anti-tumor activity. Specific refinements to standard RECIST criteria in the setting of HCC clinical research were initially introduced at the time of the SHARP trial comparing sorafenib versus placebo. Subsequently, in 2008, a group of experts was convened by the American Association for the Study of Liver Diseases (AASLD) produced formal amendments to RECIST. The re-sulting criteria were named modified RECIST (mRECIST) for HCC. Most of the changes were based on the recommendations produced at the time of the SHARP trial to prevent incorrect diagnoses of progression. In addition, the mRECIST criteria adapted the concept of viable tumor proposed by the 2000 EASL guidelines to comply with the unidimensional approach of standard RECIST, by recommending to measure the longest diameter of the viable portion of the target lesions. mRECIST appears to have broader applicability with respect to the EASL criteria. Several recent investigations conducted in the United States, Europe, and Asia have shown that assessment of tumor response by mRECIST predicts survival in HCC patients receiving liver-directed therapies.

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12:20 – 13:00 Special Lecture: Could modern radiotherapy cure liver malignancies

Prof. Jürgen P. Debus, M.D., Ph.D

Professor and Chairman Department Radiation OncologyUniversity Hospital Heidelberg (Germany)

Jürgen Debus , Daniel Habermehl, Stephanie Combs, Klaus HerfarthIntroductionClinical experience with radiotherapy of patients with hepatocellular carcinoma (HCC) and liver metastases has grown significantly in the past decade. Advances in imaging and ra-diation techniques allow to conform high doses to focal lesions and help to avoid radiation-induced liver toxicity (RILD).

MethodImaging of the tumor is the key to successful treatment with radiotherapy. While imag-ing of liver metastases is well established it is often challenging to visualize hepatu- cellular carcinoma because of the lack of inherent contrast between liver tumors and the surrounding liver. With the advent of 3-dimensional conformal radiation treatment (CRT), partial liver irradiation became possible. Stereotactic body radiation therapy (SBRT)is a further development with highly focused, stereotactically localized high-dose RT delivered in a few fractions. However, despite these advances in photon radiotherapy, signifi-cant volumes of liver still receive low doses of radiation particularly in patients with limited functional liver reserves. Due to their inverted dose profile and the high local dose deposi-tion within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effec-tiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed. Currently particle therapy with protons and carbon ions is the most sophisticated delivery technique. Modern delivery techniques allow to take into account breathing motion and changes in the liver position day to day.

ResultsWith stereotactic body radiotherapy, very high local control rates have been observed, with minimal toxicity in selected patients with liver metastases. Patients most likely to benefit from SBRT are those with liver confined disease, and metastases with a distance of more than 1.5 cm to the liver surface. For both HCC and liver metastases, the best outcomes after radiation therapy are found in patients with fewer than 3 lesions that are <6 cm in size, with intact liver function and no extrahepatic metastases. There is a strong rationale for using radiation therapy in patients unsuitable for or with expected poor outcomes after standard local-regional therapies. Radiation Therapy is integral part of the Guidelines in many Asian countries. Japanese Data on the evaluation of proton and carbon ion radiation therapy showed promis-ing results for patients with HCC. In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control. Primary endpoint is toxicity, secondary endpoint is progression-free survival and response. First experiences will be reported

ConclusionModern radiation therapy techniques allow to treat patient with malignant diseases of the liver. Whereas radiation therapy is part of the treatment guidelines in Asian countries, the role of modern radiation technique is still evaluated in clinical trials in western countries.






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14:10 – 14:30 Molecular signature of prognosis and outcomes in hepatocellular carcinoma

Prof. Josep M. Llovet, MD

Professor of Research BCLC Group, Liver UnitHospital Clínic Barcelona (Spain)Director of the HCC Research Program Professor of Medicine Mount Sinai School of Medicine New York (USA)

Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem with 700,000 new cases per year worldwide. Most HCCs arise within a pre-viously damaged liver; chronic hepatitis (B and C) and alcohol abuse being as the leading environmental causes for the underlying liver disease1,2. Despite recent advancements in the management of the disease, as the identification of sorafenib as the first efficatious mo-lecular therapy3, the overall prognostic of these patients is dismal. Two major advancements could critically improve the outcome of patients with this neoplasm: First, the identification of critical molecular subclasses with different prognostic implications. Identification of biomarkers able to define sub-groups of patients with dismal prognosis will translate into better thera-peutic strategies and allocation of resources4. Second, the identification of key genetic or epigenetic drivers of specific subclasses will enable development of more personalized treat-ment algorithms. Both challenges are hampered by the complexity of the molecular basis of liver cancer.

Accurate prognosis prediction in oncology is critical. In patients with HCC, unlike most solid tumors, coexistence of two life-threatening conditions such as cancer and cirrhosis difficult prognostic assessments. The Barcelona-Clinic Liver Cancer algorithm is the accepted staging system for HCC, but it currently has not incorporated molecular data4. Genomic profiling has already demonstrated its prediction benefits in other malignancies5. In fact, some signature-based chips are currently under evaluation as predictors of therapeutic response in oncology (e.g., breast). Many studies have proposed molecular classifications of HCC using mRNA-based gene expression profiling, obtained from tumor or non-tumoral adjacent cirrhotic tis-sue and are reviewed elsewhere6-10. Gene signatures from the tumor capturing biological signals related to proliferation and cell cycling (e.g., “proliferation class”6, “G3”7) seem to identify patients with more aggressive disease. Moreover, patients with tumors supposedly derived from progenitor cells tend to have worse prognosis (e.g., “hepatoblast signature”8, “EpCAM”9,) (Table 1). Poor prognostic signatures generated so far have not been specifically associated with any risk factor, such as HCV or HBV, or underlying pre-neoplastic condition. In addition, gene signatures obtained from the adjacent non-tumoral tissue (poor-survival signature), capturing the “field effect” concept, strongly predict outcome in HCC10. In an effort to integrate all the available prognostic signatures in a unified validation effort, we analyzed the prognsotic relevance of 22 gene signatures with reported prognostic impact in HCC (18 tumoral and 4 from cirrhotic tissue) in a cohort of 287 HCC patients undergoing resection11. The tumor signature G3-proliferation and the adjacent signature of poor-survival emerged as independent predictors of recurrence along with satellites.

Other efforts are ongoing to establish biomarkers of prognosis in HCC, such as miRNA (e.g., miR-26a12) or epigenomics, areas in which promising preliminary data is thoroughly explored. The challenge for upcoming years will be to precisely depict genomic predictors (e.g., gene signatures, miRNA or epigenetic biomarkers) at each stage of the disease and their spe-cific influence to determine patient prognosis. Finally, strict rules for incorporating prog-nostic or predictive markers into clincial practice have been published13. According to these rules, acceptable biomarkers should be obtained from randomized investigations, as is the case with KRAS status and response to cetuximab in colon cancer. Only in particularly compel-ling circumstances can prognostic or predictive markers tested in cohort studies be adopted

HEPATOCELLULAR CARCINOMA Chair: J.-A. Koch (Essen) / J. Bruix (Barcelona)






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in clinical practice. Thus, it is recommended to incorporate biomarkers for the management of HCC when the following requirements are met14: 1. Demonstrate prognostic prediction in properly powered randomized studies or in training and validation sets from cohort studies, 2. Demonstrate independent prognostic value in mutivariate analysis including known clinico-pathological predictive variables, and 3. Confirmation of results using the same technology in an external cohort reported by independent investigators.

Table 1Relevant mRNA and mi-RNA-based alterations with prognostic impact in HCC patients.

Molecular alteration Clinical significance REMARK recommendations* Status†

Poor-survivalsignature (186 genes) 10 #

Poor survival OK EV

EpCAM signature 9 Poor survival OK EV

Hepatoblast signature 8 Poor survival OK IV, EV

G3 subclass 7 Poor survival - IV, EV

Down-regulation miR-26a 12 Poor survival OK EV † Current status in terms of clinical implementation (T: need further preliminary prognostic evaluation, IV: lacks internal validation, EV: lacks external validation)# Genomic signature obtained from non-tumoral tissue

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14:30 – 14:50 Transplantation in HCC: Which patient, which criteria

Prof. Vincenzo Mazzaferro, MD PhD

G.I. Surgery and Liver Transplant UnitNational Cancer Institute Milan (Italy)


14:50 – 15:10 Hepatocellular carcinoma downstaging to transplantation

Prof. Christian Toso MD

Department of Visceral Surgery and Transplantation University Hospital of Geneva (Switzerland)

Liver transplantation is the best treatment option for patients with early non-resectable hepatocellular carcinoma (HCC), and Milan criteria are the most widely accepted selection tools (one HCC ≤5 cm or ≤3 HCCs each ≤3 cm). The expansion of these criteria is a matter of debate, including the use of downstaging prior to listing candidates with larger HCCs.

Most published data suggests however that liver transplantation after downstaging achieves similar outcomes as transplantation within Milan criteria, with three and five-year survivals of 80-100% and 55-94%. Thanks to the power of selection of downstaging, candidates with the most biologically favorable HCCs can be selected among higher risk patients. As a con-sequence, aggressive local and/or systemic HCC treatments should be offered to all patients beyond transplant criteria (downstaging and palliative managements are anyway similar). A number of studies suggest that among downstaged patients, those with the most aggressive original HCCs (AFP >1000 ng/ml) are less likely to reach transplantation criteria, but have better post-transplant outcomes. Based on these observations, no AFP limit should be set when entering a downstaging/transplantation program (further investigations remain to be performed regarding HCC size/volume).

Until now, Milan criteria have been used by most investigators in order to define the success of downstaging. Based on the observation that both advanced (high volume) and aggressive (high AFP) HCCs have worse post-transplant outcomes, it appears important to set both morphological (Milan, up-to-seven or Total Tumor Volume ≤115 cm3) and biological (AFP ≤400 ng/ml) limits for defining access to listing/transplantation. To illustrate, a patient re-plying to local HCC treatment according to size, but failing to decrease AFP levels, is at risk of extra-hepatic disease and should be excluded from transplantation.

Finally, the strongest predictor of success after transplantation in downstaged patients is the time between downstaging and transplantation. It should be long enough in order to avoid transplanting patients with early recurrences (they would recur anyway with or without transplantation), but not too long in order to save patients with more indolent diseases. Over-all, a 3-6 months minimum waiting time appears required.

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15:10 – 15:30 Hepatocellular carcinoma: Resection or ablation

Prof. Hyunchul Rhim, MD, PhD

Department of Radiology Samsung Medical Center, SungkyunkwanUniversity Seoul (Korea)

Resection is the first-line treatment option for patient with solitary HCC and well-preserved liver function. Additional indication of resection for patients with multifocal tumors meeting Milan criteria (<3 nodules <3 cm) or with mild portal hypertension not suitable for liver trans-plantation require prospective comparisons with loco-regional treatments.

Local ablation with radiofrequency or ethanol injection is considered the standard of care for the patients with BCLC 0-A tumors not suitable for surgery. Both techniques achieve com-plete responses in most of cases with good long-term outcomes for the patients with very early stage HCC. Ethanol ablation is recommended in cases where radiofrequency ablation is not technically feasible. Microwave or cryo-ablation has its own advantage, but is still under investigation.

Despite many comparative studies to elucidate whether RFA can compete with surgical re-section as a first-line treatment for patients with early HCC (BCLC A), there is no robust data to support RFA as replacement of resection at the moment. However, ablation has been nearly 100% effective in HCC smaller than 2 cm (BCLC 0) and survival is almost similar after resection or ablation. Hence, if transplantation is not an option, ablation would become the first-line option and surgical resection would be justified only in patients with failure of or contraindication to ablation, which was revised on BCLD guideline in 2011.

In summary, resection or ablation is the comparable treatment methods for managing the patient with early stage HCC, not suitable for transplantation. Although only RCT with large series can answer whether RFA can replace surgical resection in early stage, it will be not so easy to be performed because of modest difference in the therapeutic efficacy of both treat-ments and the intrinsic complexity of the patient with chronic liver disease. More importantly, we need to keep in mind that HCC could be managed successfully only by multi-modality rather than single modality approach.

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15:30 – 15:50 Hepatocellular carcinoma – Intraarterial therapies: SIRT or TACE

PD Tobias F. Jakobs, M.D.

Head of the Department of RadiologyHospital Brothers of Charity, Munich (Germany)

Abstract:Interventional radiology offers palliative treatments that diminish or destroy tumors in pa-tients, which can prolong survival and improve patients’ quality of life. These treatments are generally used for patients with primary liver cancer or isolated metastases in the liver secondary to colorectal cancer or neuroendocrine tumors, who are not candidates for surgical resection or radiofrequency ablation of the tumors. Unfortunately, the majority of patients with these conditions are not candidates for surgery, either because of the extent of disease or because of comorbidities.Treatments for oncological palliation in HCC patients include Transcatheter Arterial Chemo Embolization (TACE), and Selective Internal Radiation Therapy (SIRT). TACE is a treatment that is offered to patients with advanced hepatocellular cancer (HCC) whose tumors are too large to be treated by thermal ablation or surgical therapy. TACE may also be used for colo-rectal or neuroendocrine metastases to the liver. SIRT can be offered to patients advanced liver metastases due to colorectal cancer or neuroendocrine tumors and no or limited extra-hepatic disease. It may also be used to treat patients with large or multifocal HCC tumors.

Trans Arterial ChemoEmbolization (TACE):TACE is recommended for treatment of advanced HCC, with tumors that are too large or too numerous for thermal ablation or surgical resection. TACE has level I support for the treat-ment of unresectable HCC with evidence for significantly higher rates of survival after TACE at one (82% versus 63%) and two years (63% versus 27%) compared to those receiving sup-portive care. The Society of Interventional Radiology position statement reports that TACE is a safe, proven, and effective technique for the treatment of a number of liver malignancies including HCC. It may be used as a bridge to liver transplantation and may be used prior to thermal ablation as reduction of tumor vascular supply by embolization that enhances the effectiveness of tumor ablation.TACE is also considered to have a palliative role for patients with colorectal liver metastases and neuroendocrine tumor metastases without evidence of significant extrahepatic disease. The treatment is delivered via a catheter into the hepatic artery, under imaging guidance, which selectively delivers the chemoembolization agents to tumors in the liver because they have an arterial blood supply, whereas the liver parenchyma is primarily supplied by the portal circulation. The traditional TACE cocktail includes lipiodol, a compound that is selec-tively taken up and retained by HCC cells and some hepatic metastases and which effectively increases the concentration and retention of chemotherapeutic agents. More recent formula-tions use drug-eluting microspheres instead of lipidiol. Cancer cell death occurs by a combi-nation of ischemia and response to chemotherapy.Current therapy guidelines limit TACE to patients with adequate liver function and no vas-cular invasion or extrahepatic spread. Survival rates of 57-82% and 31-63% at one and two years, respectively, have been reported for patients treated with TACE, compared to 31-63% and 11-27%, respectively for those who received best supportive care.

Selective Internal Radiation Therapy (SIRT)SIRT is an effective palliative therapeutic option for patients with large or multifocal hepatic metastases from colo-rectal cancer, neuroendocrine tumors, or HCC. In SIRT, resin or glass microspheres loaded with yttrium-90, are injected into the right and / or left hepatic artery. One treatment consists of a few million (glass) or 40 to 80 million (resin) microspheres,ranging in size from 20 to 60 microns and carrying 2500 Bq (glass) or 50 Bq (resin) of Yttrium-90, which has a half-life of 64.1 hours and an average energy of 0.94 MeV (correspond-ing to a maximum range of 1.1 cm within tissue and a mean path of 2.5mm). The treatment

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results in tumor embolization and delivers a high dose of targeted radiation (a type of brachy-therapy) to tumors while minimizing radiation damage to normal surrounding hepatic paren-chyma and adjacent tissues.Patients who are candidates for SIRT must have tumor disease largely confined to the liver, adequate liver function (bilirubin <2 mg/dl), good performance status (Eastern Cooperative Oncology Group status <2), in general good portal vein patency, and adequate renal function (eGFR >30 ml/min/m2). It is also imperative that the patient be assessed to prevent radio-activity-induced damage to the lungs or the stomach.A non-randomised comparative study of 86 patients, with 43 treated by SIRT and 43 treated by TACE, reported overall median survival of 42 months in the SIRT group compared with 19 months in the TACE group. A non-randomised comparative study of 71 patients, with 27 treated by SIRT and 44 treated by chemo-embolisation, reported 1-year survival rates of 16% (4/27) in patients treated by SIRT compared with 20% (9/44) in patients treated by chemo-’embolisation. The non-randomised comparative study of 86 patients reported a partial response (WHO criteria) in 61% (26/43) of the patients treated by SIRT (median follow-up of 34 months) and 37% (13/35) of the patients treated by TACE (median follow-up of 52 months). This difference was not significant (p=0.07).Furthermore, the study reported downstaging from stage T3 to stage T2 in 58% (25/43) of patients in the SIRT group and 31% (11/35) of patients in the TACE group at a median time of ‘within 6 months. Additionally, a median time to overall progression of dise ase of 33months in the SIRT group compared with 13 months in the TACE group was reported.A case series of 291 patients treated by SIRT reported that 12% (34/291) of patients under-went treatment with curative intent: 32 went on to have liver transplants and 2 had resection of their tumours (median follow-up 31 months).SIRT is an exciting new addition to the armamentarium for the regional management of HCC and other liver tumours. The response rates to SIRT are sufficiently high to make it likely that the treatment will have some useful impact on the management and survival of patients with this disease. Considerably more information concerning its place and value in treatment will become available as more centres make use of SIRT.

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15:50 – 16:10 Combination of liver directed therapies with systemic therapies

Prof. Jordi Bruix, MD

Head of BCLC groupHospital Clinic University of Barcelona (Spain)

Established liver directed therapies for hepatocellular carcinoma (HCC) include surgery (re-section and transplantation), ablation and transarterial chemoembolization (TACE). Optimal candidates for surgery and ablation are those patients with an early stage disease, while candidates for TACE are those with larger and/or multifocal disease. In all options, vascular invasion should not be present and extrahepatic spread should be ruled out. Surgery and ablation achieve a high rate of complete response, while most patients treated with TACE ex-hibit partial response with some residual active tumor areas. Systemic treatments have been evaluated as coadjuvant and as adjuvant to increase treatment efficacy or reduce recurrence/progression rate after treatment. Unfortunately, none of the attempted strategies has shown unequivocal proof of benefit.

Conventional chemotherapy has failed prior and after resection and the same applies to the liver transplant setting.mTOR immunosuppression has been suggested to reduce recurrence, but trials confirming this suggestion are lacking. Encouraging effects have been reported with retinoids and interferon to prevent recurrence after resection and ablation. However, the data are derived from unplanned subanalysis with reduced simple size and metanalysis of limited strength. Thus, no strong recommendation can be given about their use. Ongoing trials are testing sorafenib after resection/ablation in a large international trial including more than 1000 patients and data are eagerly awaited.

The field that has gained more attention in recent years is the combination of antiangiogenic agents with TACE. This treatment induces a major relaeas of angiogenic factors and these are known to have a negative impact in survival. Thus, there is a rationale to combine these agents with TACE. Several studies have shown that the combination is safe in properly se-lected patients. Unfortunately, the data obtained in randomised phase 2 investigations testing sorafenib (started before or after TACE) have confirmed the safety of their combination but despite showing a positive trend as per delaying tumor progression, the strength of the data have not reached the magnitude to develop phase 3 trials targeting survival. Failure to delay progression after TACE while this is oberved in advanced stage is difficult to justify. However, it may be that the efficacy of sorafenib is counterbalanced in a coadjuvant research trial by the several confounding issues that may emerge in the field of TACE. These include the as-sessment of treatment related adverse events leading to trial interruption, criteria to repeat/cancel TACE and patients/inestigators expectancy to obtain benefit from sorafenib at later stages after initial disease control by TACE.

In summary, the field of systemic therapy in combination with liver directed treatments keeps being an area of active research. If any novel approach shows activity and survival benefit, the impact in the life expectancy of the patients would represent a major clinical breakthrough.

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16:10 – 16:30 Systemic therapy for HCC: State-of-Art

Prof. Ronnie Tung-Ping Poon, MBBS, MS, PhD

Suen Chi-Sun Professor of SurgeryChair Professor of Hepatobiliary and Pancreatic SurgeryThe University of Hong Kong (China)

Hepatocellular carcinoma (HCC) is a hypervascular tumor with rapid growth and high pro-pensity for vascular invasion. Both tumor cell proliferation and tumor angiogenesis plays an important role in the growth and progression of HCC. High tumor expression of growth factors and signaling proteins related to tumor cell proliferation and angiogenesis has been shown to be associated with poor prognosis in HCC patients. HCC is generally a chemoresistant tu-mor and previous studies on systemic cytotoxic chemotherapies have failed to demonstrate survival benefit in advanced HCC patients. Furthermore, cytotoxic drugs are not well-tolerated by HCC patients who often have associated cirrhosis. Inhibition of signaling pathways in-volved in HCC proliferation and angiogenesis represents the most promising strategies that may be effective for HCC. Thus far, the best clinical evidence of efficacy of molecular targeting therapy in HCC comes from two phase III randomized placebo-controlled trials of sorafenib, a multikinase inhibitor of Raf kinase and VEGF receptors, which significantly pro-longed patient survival compared with placebo. Sorafenib is currently the only approved therapy for advanced metastatic HCC. However, the tumour response rate to sorafenib monotherapy is less than 5% in both trials, and the survival benefit is limited. Newer targeting agents are needed to improve the systemic therapy of HCC. Unfortunately, a few recent phase 3 trials on other molecular targeting agents sucg as Sunitinib and Brivanib have failed to demonstrate any benefit over Sorafenib. Combination of Sorafenib with Erlotinib has also failed to show additional benefit in a phase 3 trials. Currently on-going phase 3 trials are evaluating second-line therapy after Sorafenib failure using Everolimus and Ramucirumab. Combination of Sorafenib and chemotherapy is also being studied. Novel agents targeting new signaling molecules such as cMET and GC33 are being investigated in phase 1 and 2 trials. The landscape of systemic therapy for HCC may chance in the near future with the results of some of these trials coming up.






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17:10 – 17:30 Curative and palliative surgery

Prof. Hauke Lang, M.A.

Director of the Clinic for General-, Visceral- and Transplantation SurgeryUniversity Hospital Johannes Gutenberg-Universität Mainz (Germany)

Single center experience with 49 resections in 64 patients over a 4-year periodJanine Baumgart, Fabian Bartsch, Philipp Kaudel and Hauke LangDepartment of General, Visceral Surgery and Transplantation, University of Mainz, GermanyBackground

Due to the lack of early clinical symptoms, ICC is mostly diagnosed at a locally advanced stage and therefore often requires an extended surgical approach. Although a complete re-section offers the only chance for cure and an improvement of long-term survival, high re-ported morbidity and mortality rates repeatedly raised the question, whether extended liver resections with complex biliary and/or vascular reconstructions are justified.

MethodsBetween January 2008 and December 2012, a total of 64 patients with ICC underwent surgical exploration in our department. Data of patients undergoing liver resection (n=49), especially focused on extended hepatectomies (n=19), were analyzed retrospectively with regard to pa-tients’ characteristics, operative details, perioperative morbidity and mortality, clinical out-comes and pathological findings.

ResultsResectability rate was 49 of 64 (76,5 %). 19 patients received an extended hepatectomy (29,7%) including 9 extended right and 7 extented left hepatectomies, 2 ALLPS (Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy) and 1 mesohepatectomy. Further-more, in 25 patients additional procedures were performed as following: partial resection of diaphragma (n=4) and pericardium (n=1), resection of hilar bifurcation (n=10), caudate lobe resection (n=13), right adrenalectomy (n=1), partial resection of vena cava (n=8), resection and reconstruction of major hepatic veins (n=9) and portal vein resection (n=8). Tumors were solitary in 30 patients. Complete tumor removal (R0) was achieved in 42 patients (85,7%). Postoperative complication rate requiring radiological intervention or reoperation was 14% (n=7) and 6% (n=3), respectively. 30- and 60-day mortality were 4,7 % and 1,6%.

ConclusionAchieving a complete tumor removal in 85,7% which leads to a prolonged survival in patients with ICC, the presented results support the opinion that an extended surgical approach is justified in well selected patients. Nevertheless, the collected data with particularly regard to morbidity and mortality rates approve the need for sufficient preoperative assessment of resectability.






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CHOLANGIOCARCINOMA Chair: M.K. Walz (Essen) / A. Vogel (Hannover)

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17:30 – 17:50 Intraarterial therapies: SIRT or TACE

Prof. Thomas K. G. Helmberger, MD

Director of the Department of Radiology, Interventional Radiology, Neuroradiology and Nuclear medicineKlinikum Bogenhausen, Munich (Germany)

Cholangiocarcinoma (CC) is the second most common primary hepatic tumor accounting for 10 – 20% of primary liver tumors. Surgery is the therapy of choice in all three types of CC – the peripheral mass forming, the periductal, and the intra- or extrahepatic ductal type. However, the overall curative resection rate is low and the prognosis is poor with recurrence rates of about 60 % after resection. If only chemotherapy can be applied the overall survival is less than 1 year in most of the cases.

Most CCs will develop remote metastases only at a later stage what justifies the rational for local treatments as long as the tumors are confined to the liver. While in the ductal types of CC the therapeutic endeavor is mainly ruled by endoscopic procedures the more peripheral, mass forming types will be target of percutaneous or transarterial ablative techniques. In most of these cases, tumor size and vascularization will make the specific tumor more eligible for transarterial therapies as chemo- (TACE) or radioembolization (RE) than for local thermal ablation.Up to now, only limited data are available for both techniques for the treatment of CC, mainly presented via cohort studies. With respect to very different inclusion criteria, very differing patient conditions, and various technical regimens the median survival rate that could be achieved with both techniques ranged between 10 and 20 months, whereas in single cases a survival of about 30 months could be achieved. So far, in several studies prognostic factors as patients performance status, tumor load, and tumor vascularization could be identified. Nevertheless, even if the current available data on TACE and RE in CC are quite encouraging substantial comparative studies are still missing defining the role of these techniques within the therapeutic concept for CC.


17:50 – 18:10 Systemic therapies for cholangiocarcinoma: State of the art 2013

Prof. Andrew X. Zhu, MD, PHD

Director, Liver Cancer ResearchMassachusetts General Hospital Cancer CenterHarvard Medical School, Boston (USA)

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.Biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most pa-tients with BTC will present with unresectable or metastatic disease. Although the standard systemic combination chemotherapy approaches are emerging, the prognosis remains poor with a median survival of less than one year. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early stage clinical trials with targeted thera-pies appear promising, though the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. The author will discuss the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.

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10:20 – 10:40 Endoscopic treatment options for cholangiocarcinomas

Prof. Klaus Mönkemüller, MD, PhD, FASGE

Department of Medicine, Division of Gastroenterology and HepatologyUniversity of Alabama, Birmingham (USA)

Klaus Mönkemüller, MD, PhD, FASGE, Jay Ramesh, MD, FRCP, FASGE, C. Mel Wilcox, MD, MPH, FASGEBasil Hirschowitz Center for Endoscopic Excellence, Division of Gastroenterology, Hepatology, University of Alabama at Birmingha,m, Alabama, USA

Cholangiocellularcarcinomas (CCC) account for approximately 2-3% of all cancer diagnoses with an incidence of about 2.1/100,000. About 60% of cases occur in patients over the age of 65 years, with a similar distribution between women and men.

CCCs are heterogeneous groups of tumors of the bilary tract. In 1965 Gerald Klatskin de-scribed the distinct characteristics of hilar CCC arising at the hepatic bifurcation. Since then Klatksin tumor has been synonymous with CCC. However, there are several types of CCCs based on their anatomic location, and Klatskin tumors comprise only 10% of CCCs. The most common type is the peri-hilar variant (pCCC) (50%), followed by the distal type (dCCC) (40%) and intrahepatic (iCCC) (10%). Klatskin tumor is a type of pCCC. Because some CCCs arise from hepatic progenitor cells, some authors prefer to call these tumors cholangiocarcinoma (CCA).

Therapy for CCC is based on the type, location and size of tumor. Whereas small dCCC and hCCC can and should be treated using radical surgical resection, mass tumors located inside the liver or large or metastatic extrahepatic tumors can only be treated with chemotherapy using a combination of gemcitabine and cisplatin.

If the lesions are causing bilary luminal obstruction with resulting jaundice, endoscopic ther-apy using stents (plastic or metal) is a definite option. Plastic stents vary in caliber, length, material, and configuration depending on their design and intended application. The pre-ferred plastic stents for biliary decompression in pCCC and dCCC are “large” diameter (i.e. 10 or 11.5 Fr) polyethylene or Teflon stents. The general rule is to apply the largest possible stent that can traverse the stricture and, if possible, place several stents. The major disadvan-tage of plastic stents is their high rate of occlusion (about 75% within 90 days of placement). Thus, if the patient is expected to survive longer than 3 months the use of self-expanding metal stents (SEMS) is indicated. The main advantage of SEMS is their larger diameter ( 6, 8 and 10 mm) and thus longer patency rate. Most SEMS for malignant biliary strictures are made of Nitinol, a superelastic nickel-titanium alloy with thermal shape memory, a property of reassuming a predetermined shape through heating. As these stents are placed through the endoscope fluoroscopy is always needed. Ideally, SEMS should be well visualized during fluoroscopic placement. Thus, the radiopacity of some metal stents is enhanced by incorpo-rating other metals into the body or the ends of the stent. Membrane-covered SEMS offer the potential advantage of preventing tissue ingrowth. Whereas the use of SEMS is clearly indi-cated for distal and hilar strictures, the use of double metal stenting into both intrahepatics is less well studied. Nonetheless, achieving drainage of both intrahepatic ducts is associated with less cholangitis, jaundice and morbidity.

In recent years, intrabilary photodynamic therapy (PDT) delivered through the duodenscope has emerged as a good palliative measure in some pCCC and dCCC. Indeed, some data have studies that survival may be improved in patients undergoing PDT.

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09:00 – 09:20 The Four Melanomas

Prof. Ulrich Keilholz

Deputy Director of the Charité Comprehensive Cancer CenterCharité, Berlin (Germany)

Until several years ago, metastatic melanoma has been a disease without a treatment option with proven impact on survival. DTIC was the reference treatment, based on moderate efficacy and low toxicity. Interleukin-2 and vaccines were immunologic treatment alternatives, and first-line experimental treatment was explicitely accepted. For metastatic mucosal and uveal melanoma, no reference treatment was defined. During the past three years, thie situation has profoundly changed, based on molecular understanding of four different melanoma enti-ties and development of novel therapies. Cutaneous melanoma has been devided into solar and non-solar melanoma. Solar melanoma predominantly arises on skin with intermittent UV exposure and frequently harbors activating braf or nras mutations. Non-solar cutaneous melanomas develop on skin areas rarely exposed to UV and typically show disruptive muta-tions of p53. In addition, a fraction of melanomas arising in areas of the skin with chronic UV exposure and from mucous membranes displays activating mutations of ckit, and, lastly, uveal melanomas are characterized by activating mutations of GNA11 and GNAQ. These dis-coveries have promptet rigorous development of targeted drugs and several compounds have proven to be highly active in inducing remissions and improving survival. These specifically include agents targeting mutated braf and also mek, and to a lesser extent ckit. Combina-tion treatment studies are under way. For uveal melanomas, targeted agents still have to be tested. In addition to the molecularly targeted agents, immune checkpoint regulators, such as antibodies directed against CTLA4 and PD1/PDL1 have been developed and initiated a solid and efficient new era of immunotherapy of metastatic melanoma. These novel treat-ment modalities have now to be tested in combinations and in sequence in order to further improve quality of life and survival of metastatic melanoma patients. The indications of liver-directed therapies and all other locoregional treatment approaches, which remain effective and important, have to be reconsidered.

MELANOMA Chair: U. Keilholz (Berlin) / D. Schadendorf (Essen)

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09:20 – 09:40 Liver metastases from melanoma

Prof. René Adam

Head of the Oncological Surgery Unit of theHepatobiliary Center Paul Brousse Hospital, Villejuif (France)

René Adam1 Laurence Chiche2

(1) AP-HP Hopital Paul Brousse, and Univ. Paris-Sud, UMR-S 776, Villejuif, France(2) Hopitaux Universitaires de Bordeaux, Service de Chirurgie Digestive, Maison du Haut Lévèque 33604 PESSAC

Liver metastases are a frequent mode of recurrence of choroid melanoma (60-90% of cases) and much less frequently of cutaneous melanoma (5-15% of cases). The outcome of metastatic melanoma is poor with median survival rates of 6-9 months and a 5-year survival inferior to 10%. The clinical presentation relies on the discovery of LM in the follow up of a known melanoma or of a multinodular hepatomegaly from an undiagnosed melanoma. Despite the improvements of imaging, there is frequently an undersetimation of the lesions.

The role of hepatic surgery is still questionned and the number of reported cases in the litterature is relatively limited (less than 200) with only 8 series with more than 10 patients (14-40 patients). Median survival rates vary from 25 to 29 months with few patients alive at more than 5 years. The most important series in the litterature is that we published in 2006 on behalf of the French surgical Association (AFC). 148 patients were reviewed during a study period of 21 years (1983-2004) mainly with uveal melanoma (104 patients) and cutaneous melanoma (44 patients). The primary had been treated surgically in half of the patients. The majority of patients (91%) were metachronous with a delay between the diagnosis of the primary and liver surgery of 61 months. Hepatectomy was limited (< 3 segments) in 46%, R0 in 72% of patients. Operative mortality was 2.9% and recurrence occured in 82% after a mean delay of 9.6 months. Overall 5-year survival was 20% no different between cutaneous (22%) and uveal melanoma (20%). Solitary metastases were associated with much better survival (median 33.6 months) than 2-3 metastases (19.9 Mo) or > 3 metastases (16.8 Mo). Repeat hepatectomy also allowed better survival compared to single hepatectomy (45% vs 18%). However, at multivariate analysis, the time interval between treatment of the primary and the diagnosis of liver metastases was the only independent factor of prognosis, with 2 cut-off at 12 and 24 months.

• Inconclusion:Longtermsurvivalafterliverresectionformetastaticmelanomaremains poor.

• Nevertheless, it seems that an extremely selected population of patients presenting • with1to3metastaticnodules, • after2yearsofthetreatmentofprimarytumor • andwho could undergo a limited hepatectomy could benefit from a surgical treatment and even from a rehepatectomy

• Incutaneousmelanoma,recurrenceseemsconstant…






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09:40 – 10:00 Intraarterial therapies: SIRT or TACE

Prof. Philippe L. Pereira

Director of the Department of Radiology, Minimal-invasive Therapies and Nuclear medicineSLK-Kliniken Heilbronn GmbH (Germany)

There are approximately 54,000 new cases of malignant melanoma diagnosed annually in the United States, of which slightly more than 6% are primary ocular melanom.Metastatic disease occurs in 30% to 60% of patients with ocular melanoma, and only 9% of patients with hepatic metastasis are eligible for resection or ablation, predominantly because of the large number of hepatic metastases. Unresectable or unabladable hepatic metastases represent the sole or major life-limiting component of progressive disease in over 80% of patients with ocular melanoma who recur. Overall survival with best supportive care is approximately 3 months, with salvage chemotherapy, the median survival is between 2 and 7 months, and one-year survival is approximately 10%.

A variety of chemotherapeutic drugs such as dacarbazine or cisplatin, and immunotherapeutic agents such as interleukin-2, interferon or monoclonal antibodies, as well as the antiangio-genic agent thalidomide, have been administered either alone or in combination and have not been associated with remarkable better survival. New systemic therapeutic options with monoclonal antibody (Ipilimumab) or inhibitor of BRAF-kinase (Vemurafenib) have shown promising results in current clinical applications.Thus, local treatment strategies for patients with unresectable/unabladable hepatic me-tastases have been developed because natural history of liver metastatic disease justifies aggressive measures to control hepatic tumor progression. The best results with local liver therapies have been obtained with transarterial chemoembolization (TACE) and isolated hepatic arterial infusion (HAI). TACE and HAI are performed by administer chemotherapy intraarterially (HAI) eventually followed by infusion of absorbable or non-absorbable particles (TACE) through percutaneously placed catheters. Mavligit et al. reported results of TACE using cisplatin for patients with liver metastases and obtained a 50% response rate with a median survival of 11 months. Leyvraz et al. treated 31 patients with HAI of fotemustine, 100 mg/m2, over four hours via the hepatic artery. The overall response rate (all partial responses) was 40%, the median duration of response was 11 months, and the overall sur-vival was 14 months. Pretreatment tumor burden has been found to be an important predictor of response after TACE.A few centers have evaluated a new regional therapy system for unresectable hepatic malig-nancies in which 5-fluorouracil or doxorubicin are administered via the hepatic artery and the venous effluent of the liver is collected and filtered using percutaneously placed catheters, the so called isolated hepatic perfusion (IHP) has been under clinical evaluation in a number of phase I and II studies. Twenty-nine patients with ocular melanoma metastatic to liver have been treated on a phase II study (99-C-0123) using IHP with hyperthermia and 1.5 mg/kg melphalan for 60 minutes. Of 29 assessable patients there were 2 radiographic complete responses (7%) of 10+ and 12 months duration and 16 partial responses (55%) with a median duration of response of 10 months. Of note 9 patients (31%) had a minor response that is a 25% to 49% reduction in the size of their tumors indicating some antitumor activity in almost everyone who underwent treatment. Overall data indicates that IHP can result in regression of advanced ocular melanoma in most patients but that progression of systemic disease occurs in the majority of patients. The advantages of this approach are that the treatment can be delivered without a major operative procedure and filtration of the hepatic venous effluent can reduce systemic expo-sure of chemotherapy compared to HAI alone, by 80 to 90%. In preclinical rabbit and porcine studies, the doxorubicin mean area under the concentration time curve in nmole/min/ml was reduced from 270±112 to 16.9±8.4 when the filtration system was used and was associated with significantly lower tissue levels in peripheral organs. There was an approximately 20% decrease in cardiac output when animals were placed on hepatic venous hemofiltration, most






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likely due to removal of endogenous catecholamines. In clinical practice with this system, hypo- tension intra-operatively has been a problem and can be adequately managed with volume support and infusion of phenylephrine, but is not possible in patients with underlying cardiac disease. Clinical trials in the United States have been conducted primarily at the Yale University School of Medicine and the M.D. Anderson Cancer Center.Drug Eluted Bead™ (DEB) is an FDA Cleared Device indicated for “Embolization of hypervascular tumors and arteriovenous malformations (AVM’s)”. The DEB can be loaded with doxorubicin, a chemotherapeutic anthracycline glycolide agent widely accepted and FDA ap-proved for treatment of liver malignancies – melanoma, -breast, and others. This novel com-bination drug/device utilizes precision chemotherapy delivery based on the flow dynamics of the malignancy (95-100% blood supply from the hepatic arterial system) when compared to the normal hepatic parenchyma (primary portal flow) to deliver cytotoxic doses of chemo-therapy. The DEB slowly releases the chemotherapy agent rather than bolusing the drug into the system (as with conventional cTACE). Thus, DEB offer the potential advantage of less toxicity and prolonged tumor exposure. Varela et al. in their recent study with doxorubicin loaded beads in 27 patients with cirrhosis-related HCC and large multifocal HCC observed a response rate of 75% (66.6% on intention-to-treat). Doxorubicin provided 1-and 2-year survival rates of 92.5% and 88.9%, respectively. Similarly, Malagari et al. in their study of 62 cirrhosis-related HCC patients who underwent sequential embolizations with doxorubicin loaded DEB (DEBDOX) at an interval of two months between each procedure observed high percentages of tumor necrosis with the second embolization. Objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) was observed in 20.9%, 61.8% and 70.8% across the three procedures. Complete response was observed in 4.8% post first pro-cedure rising to 6.7% and 10.1% after the second and third. Mean tumor necrosis ranged from 77.4 to 83.9% across the three treatments. Alpha-Fetoprotein (AFP) levels showed a mean decrease of 1123 ng/ml (95% Cl = 846-1399, p=310-11) post first session and remained stable after the 2nd and 3rd embolization (42 and 70 ng/ml decrease, respectively).Selective internal radiation therapy (SIRT) with the pure ß-emitting isotope 90Y has been used for several years to manage both primary and metastatic hepatic tumors.90Y microspheres infused into the hepatic artery concentrate in much higher doses in he-patic tumors than in the normal surrounding liver. Yttrium-90 microspheres, which have a half-life of 64.2 hours, are permanently embedded in hepatic tumors and have an average energy of 0.94 MeV. Most of the radiation dose is released over 14 days at approximately 50 cGy/min. Therefore, most of the radiation dose is administered directly to the tumor with relative sparing of the normal liver parenchyma. Corresponding to the FDA approval, most data on selective internal radiation therapy (SIRT) is available for the treatment of colorectal liver metastases.There is only a substantial amount of data on SIRT in liver metastases from neuroendocrine tumors, breast cancer, and melanoma. However, currently available data in patients with liver metastases from melanoma is quite heterogeneous with some data being obtained in a sal-vage situation. Kennedy et al. reported their experience treating a small number of patients with hepatic metastasis of uveal melanoma using 90Y radioactive microspheres. In that retrospective multicenter study, 11 patients underwent 12 SIRT procedures with a median activity of 1.55 GBq delivered per treatment. Only one patient experienced a grade 3 event, a gastric ulcer that healed uneventfully within 6 weeks with supportive care. No radiation-induced liver disease (RILD) was detected. CT and PET of hepatic metastatic lesions 3 months after treatment showed one complete response, six partial responses, one case of stable disease, and one case of disease progression in nine evaluable patients. Among the 10 patients with available clinical follow-up information, the 1-year survival rate was 80%. The relatively low response rate (one complete response, one partial response, and 18 cases of stable disease in 32 patients) in the study of Gonsalves et al. study compared with that found by Kennedy et al. may be explained in part by the inclusion of previously treated patients with bulky progressive hepatic metastatic lesions (from Gonsalves CF et al, AJR 2011; 196:468–473).






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Literature:1. Mavligit GM, Charnsangavej C, Carrasco CH et al. Regression of ocular melanoma metastatic to the liver after hepatic arterial chemoembolization with cisplatin and polyvinyl sponge. JAMA 1988; 260:974-976.2. Leyvraz S, Spataro V, Bauer J et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol 1997; 15:2589-2595.3. Alexander HR, Jr., Libutti SK, Pingpank JF et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res 2003; 9:6343-6349.4. Alexander HR, Jr., Bartlett DL, Libutti SK. Current status of isolated hepatic perfusion with or without tumor necrosis factor for the treatment of unresectable cancers confined to liver. Oncologist 2000; 5:416-424.5. Alexander HR, Jr., Libutti SK, Pingpank JF et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res 2003; 9:6343-6349.6. Ravikumar TS, Pizzorno G, Bodden W et al. Percutaneous hepatic vein isolation and high- dose hepatic arterial infusion chemotherapy for unresectable liver tumors. J Clin Oncol 1994; 12:2723-2736.7. Curley SA, Newman RA, Dougherty TB et al. Complete hepatic venous isolation and extra- corporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study. Ann Surg Oncol 1994; 1:389-399.8. Varela M, Real MI, Burrel M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 2007; 46:474-481.9. Varela M, Real MI, Burrel M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 2007; 46:474-481.10. Malagari K. Drug-eluting particles in the treatment of HCC: chemoembolization with doxo-rubicin-loaded DC Bead. Expert Rev Anticancer Ther 2008; 8:1643-1650.11. Gonsalves CF et al. Radioembolization as Salvage Therapy for Hepatic Metastasis of Uveal Melanoma: A Single-Institution ExperienceAJR 2011; 196:468–473.12. Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1. Technical and methodologic considerations. J Vasc Interv Radiol 2006; 17:1251–127813. Sacks D, McClenny TE, Cardella JF, et al. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14:S199–S20214. Therasse P, Arbruck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92:205–21615. Gray B, Van Hazel G, Hope M, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 2001; 12:1711–172016. Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microspheres brachytherapy for unresectable colorectal liver metastases: modern UA experience. Int J Radiat Oncol Biol Phys 2006; 65:412–42517. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres Theraspheres): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16:1627–163917. Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroen docrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 2008; 31:271–27918. Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol 1954; 30:969–98419. Sato KT, Omary RA, Takehana C, et al. The role of vascularity in predicting survival after yttrium 90 radioembolization of liver metastases. J Vasc Interv Radiol 2009; 20:1564–156920. Kennedy AS, Nutting C, Jakobs T, et al. A first report of radioembolization for hepatic metastases from ocular melanoma. Cancer Invest 2009; 27:682–690

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10:00 – 10:20 Modern systemic drug therapies in 2013

Prof. Claus Garbe

Head of the Section of Dermatologic OncologyUniversity Hospital Tübingen (Germany)

Essential progress has been achieved in systemic treatment of metastatic melanoma during the last few years. Based on the high prevalence of the activating BRAF V600 mutation (~ 45%) and the activating NRAS mutation (~ 15%), specific kinase inhibitors have been developed for activated BRAF and MEK. Prolongation of survival and remission rates ~ 50 % and more have been observed in phase III trials with the BRAF inhibitors vemurafenib and dabrafenib, and slightly less activity for the MEK inhibitor trametinib. Interestingly, the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib seems to postpone development of resistance and seems to be superior to single agent treatment without increasing the tox-icity. All these drugs are efficacious in patients with liver metastasis carrying the BRAF muta-tion. Another new approach is immunotherapy with immune checkpoint inhibitors, like the CTLA-4 inhibitor ipilimumab and PD-1 inhibitors. Both drugs lead to a continuous activation of functional T cell responses against the tumor, and ~ 15 – 30 % of patient seem to benefit from this kind of treatment with long term stabilization of the disease. These immunothera-pies work likewise in patients with liver metastasis.






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11:00 – 11:20 Palliative surgery in liver mets from breast cancer: Is there evidence?

Prof. Magnus Bergenfeldt

Department of SurgerySkåne University Hospital, Lund (Sweden)

IntroductionThe liver is the primary metastatic site in 12-15% of patients with metastatic breast cancer. Generally, Breast Cancer Liver Metastasis (BCLM) has been conceived as a signal of a more widespread hematogenic dissemination of the cancer. Consequently, resection of BCLM has been regarded with a lot of skepticism, and these patients have generally been treated with systemic hormone and/or chemotherapy alone. Despite new, more effective drugs such as anthracyclines, taxanes and monoclonal antibodies against growth receptors (i.e. trastzumab), definitive cure of metastatic breast cancer to the liver is rare. Furthermore, during the last decades liver resection and local ablation have evolved into safe and efficient therapy for iso-lated colorectal liver metastases. Several papers have now been published, which show that the combined use of surgical and medical oncological therapy may result in a favourable out-come for the selected subset (<5%) of patients presenting with isolated BCLM. The present paper aims at an overview of current evidence for the use of palliative surgery in BCLM.

MethodsWe searched Medline and Embase without language restriction for all original studies pub-lished during 1999-2012 regarding the use of surgical resection and/or local ablation of BCLM, using the same methodology as in a previous systematic review [1]. No Randomised controlled trials (RCT) were found. We reviewed 30 retrospective studies concerning mainly liver resection alone, i.e. five of them contained also a small group which had additional local ablation. Four studies were multicentre publications. 26 studies were single-centre studies, which contained 826 patients, i.e. median 30 (12-86) patients. Local ablation of BCLM was reported in eight retrospective studies with totally 403 patients. Seven studies used RF (one study contained a small subgroup treated with resection), but the largest study used Laser-induced interstitial thermotherapy (LITT) in 232 patients (corresponding to 54% of total).

BREAST CANCER Chair: S. Kümmel (Essen) / C. Zielinski (Vienna)

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Results1. Outcome after liver resectionThe available studies reported postoperative 2-, 3- and 5-year survivals of 58-86%, 35-79% and 21-61%, respectively. The median overall survival (MOS) was 17-74 months. Considering only studies with N>25 resulted in more conservative estimates of MOS and 5-year survival around 30-45 months and,30-40%, respectively. The largest series (N=454), a multicentre study by Adam et al., reported MOS 45 months, and 5-year survival 41%. Thus, the available literature supports use of liver resection in the selected subset (<5%) of patients with isolated BCLM, if an R0-resection is possible and the procedure adheres to current standards regarding postoperative morbidity and mortality.Intra- and/or extrahepatic recurrent disease after resection of BCLM were common, and re-currence rates (RR) of 33-78% were reported (available in 15/30 studies).

2. Prognostic factors after liver resectionPatient age was generally without significance, except in one study by Lubrano et al. General features of the primary breast cancer (site, procedure, grade, TN-stage, presence of axillary glands) have generally not been found significant for the prognosis after resection of BCLM. In some studies, the presence of hormone receptors indicated a better prognosis. Her2-status has not been associated with better prognosis “Disease interval” (between primary breast cancer and occurrence of BCLM) was studied in 12/30 studies of liver resection. It was a prognostic factor in five studies, but failed to be signifi-cant in several other studies, which used cut-offs at 6 months, 12 months and 24 months, respectively. The reasons for these differences are not obvious. A possible explanation may be statistical error, as most studies include few patients with synchronous BCLMSizes and number of BCLM were not found significant for the prognosis in most studies, al-though two studies found that more than one BCLM indicated a worse outcome. Invasion of the liver vasculature was a negative prognostic factor in one study by Thelen et al. The presence of EHD was a negative factor in the studies by Sakamoto et al. and Thelen et al., but was found non-significant in the studies by Selzner et al., Yoshimoto et al., and Adam et al. Hilar lymph node metastases were found without importance in the studies by Selzner et al., Elias et al., Sakamoto et al., and Adam et al., as were “abdominal gland metastases” in the study by Yoshimoto et al..

3. Therapy-related prognostic factors.Major liver resection was done in 6-82% of cases. Type of liver resection (minor vs. major) was not significant for the prognosis in most studies; only one study by Lubrano et al. found major resection linked to worse prognosis. The reported rates of R0-resection were 65-100 %, and it was a positive prognostic factor in four studies by Lang et al., Adam et al., Thelen et al., and Hoffman et al., although it was non-significant in the studies by Elias et al., Belda et al., Abbott et al., van Walsum et al.. Repeat hepatectomy was rarely performed, but was linked to positive prognosis by Adam et al.The importance of an objective response to chemotherapy before liver resection has been stressed by some authors. Adam et al. found that a partial response to chemotherapy pre-dicted better survival. This agrees with a recent study by Abbott et al. who found that disease progression just before hepatectomy was linked to poor survival. However, chemotherapy response was without significance in some other studies by Pocard et al., Vlastos et al., and Elias et al. However, a clear-cut disease progression during preoperative chemotherapy was an adverse factor in two studies [Treska et al., Selzner et al.], which agrees slso with a previous study by Elias [Elias et al.1991]. Taken together, the literature indicates that the response to chemotherapy will influence on the prognosis.

4. Selection of patients for liver resection.Few patients with BCLM are currently candidates for liver resection; two studies reported that they made liver resection in <1% of a breast cancer cohort. Consequently, nearly all studies reviewed were accumulated over more than a decade. Two institutions only made more than (average) five resections per year, and most of them considerably less.






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Features of the primary BC were generally not stated as criteria of selection.. “Disease interval” (between primary cancer and occurrence of metastases) is widely believed to reflect tumour biology, but it was rarely mentioned among the inclusion criteria. However, most studies had a low rate of synchronous metastasis (disease interval <6 months); the range being 0-31%, and it may be suspected that “disease interval” was inexplicitly included in the preoperative selection process in many studies.Some studies stated that they resected only patients with less than 3-5 BCLM, although several studies made liver resection also of multiple BCLM. As a consequence, the size of the largest BCLM resected also varied greatly between the studies; BCLM well exceeding 10 cm were included in several studies. However, the mean diameters of the largest BCLM were mostly in the range 3-5 cm. Liver resection in patients with extrahepatic metastases (EHD) remains a controversial issue, but the criteria varied widely. Eight studies excluded patients with EHD, while three studies accepted stable bone metastases. Ten studies accepted various EHD, as long as they were deemed resectable and/or stable on treatment.5. Outcome after local ablationThe studies of local ablation reported post- treatment 2-, 3- and 5-year survivals of 42-80%, 43-75% and 27-41%, respectively. Post-treatment MOS was 11-60 months. The rate of syn-chronous metastases was similar to the studies of liver resection, 0-19% (reported in 4/8 studies). The maximum number of BCLM was generally restricted to <5, although two studied accepted a maximum number of 8 and 13, respectively. Likewise, mean sizes of the largest BCLM were in the same range as in the studies of liver resection. However, three studies in-cluded BCLM up to a maximum diameter of 7 cm. Further, patients with EHD were accepted in all but one of the studies using local ablation. The largest study, using LITT, reported MOS 52 months, and 2-, 3-, and 5-year survivals were 80%, 63% and 41%, respectively, although this study included patients 1) unresectable, 2) unfit for or refusing resection; 3) with recurrent BCLM; 4) with bilateral BCLM; 5) with stable bone metastases. 6) with multiple (up til 13) BCLM.

ConclusionsThe available literature supports use of liver resection in the selected subset (<5%) of pa-tients with isolated BCLM, if an R0-resection is possible and if the procedure adheres to current standards regarding postoperative morbidity and mortality. Also local ablation was associated with good long-term outcome, and may be a relevant alternative for small BCLM or in patients unsuited for liver resection. The coagulation necrosis caused by RF is usually not larger than 3 cm, however, which increases the risk of local recurrence. Meloni et al. have found that RF of BCLM >2.5 cm increased the risk of death by a factor 2.1.So far resection of BCLM remains the first choice, but the less invasive nature and a lower risk of complications make RF a relevant alternative for unresectable or otherwise “”surgically unfit” patients. RCT comparing different surgical therapies are needed.“Disease interval” is generally believed to reflect tumour biology. Although, several studies show that it is a positive prognostic factor, the results are for unknown reasons divergent. We conclude that a clear-cut recommendation on disease interval cannot presently be given, and the issue needs further study.Sizes and number of BCLM were part of the selection of patients in most studies, although strict limits were seemingly rarely applied. Although one may hypothesize that especially the number of metastases may be linked to prognosis, both biologically (“biological behaviour”) and statistically (increased risk of overlooking additional, tiny metastases), data corrobat-ing its use is lacking. More obvious, sizes and number as well as distribution are important for the planning of the surgical procedure. However, the type of hepatectomy seems to be without prognostic significance, as long as an R0-resection is possible. Ercolani et al. found that involvement <25% of liver volume and tumour volume <125 ml were positive prognostic factors, which indicates the importance of R0-resection as well as leaving a sufficient future liver remnant. Repeat hepatectomy has been associated with better survival, which supportsnot using larger than necessary resections. Although liver resection was associated with a good outcome qou ad vitam, a substantial rate of the patients suffer relapse from their dis-ease. In a previous analysis, we showed that the cumulated RR was associated with the length of follow-up, and may well exceed 70% [1]. A study by Pocard et al. supports this observation.

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Thus, current data support the use of adjuvant chemo- and/or hormone therapy, probably as perioperative therapy. A strategy evaluating the effect of preoperative chemotherapy before proceeding to surgery seems well motivated. Further, the response to the preoperative regi-men may serve to guide postoperative, adjuvant therapy. In any case, surgery of BCLM in a situation with progressive BCLM should best be avoided.Although, some studies including EHD had good results, the series are small, and the rate of patients with EHD was generally low also in studies accepting such patients. In conclusion, liver resection in the presence of EHD remains an unsettled issue. Bone metastases of BC may represent a special situation. They are known to have a more indolent course, which could indicate that they should be managed differently than other EHD.To conclude: Although rarely curative, the combined use of surgery and medical oncology gives hope for prolonged survival for patients with isolated BCLM. In this context, surgery may best be described as “palliative” or an “adjunct to medical therapy”. The choice between liver resection and local ablation as well as the importance of different prognostic indicators merit further study.

1. Bergenfeldt M, Jensen BV, Skjoldbye B, Nielsen D. Liver resection and local ablation of breast cancer liver metastases – a systematic review. Eur J Surg Oncol. 2011 Jul;37(7):549-57.






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10:00 – 10:20 Transarterial chemoembolization and radioembolization in the treatment of liver tumors

Prof. Douglas M. Coldwell, PhD, MD, FSIR, FACR, FAHA

Director of the Department Vascular and Interventional Radiology University of Louisville (USA)

Both techniques rely on the arterial supply of tumors and the supply of normal tissues by the portal vein. Even though there have been no “head to head” randomized trials, I prefer to uti-lize radioembolization for the treatment of multiple liver tumors if the patient is a candidate because it is an out-patient procedure, the quality of life is generally higher, and it has been shown to prolong survival when used either initially or as second line therapy. Radioemboli-zation is usually utilized one or two times as a whole liver therapy while TACE is a therapy that is performed every 6-8 weeks and requires an inpatient admission. However, the upper limit for serum bilirubin when using radioembolization is 2mg/dl. In patients who have a bilirubin level higher than this, have a mild degree of liver failure, and in patients where there are only a few small lesions, I prefer to use TACE since the embolization can be performed superselectively without significant hepatic toxicity. It is not a question of either one or the other: Both have their place in the therapy of liver tumors.






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11:40 – 12:00 Modern systemic drug therapies in breast cancer in 2013

Prof. Christoph C. Zielinski

Director, Clinical Division of Oncology and Department of Medicine ICoordinator, Comprehensive Cancer CenterMedical University Vienna (Austria)

Systemic breast cancer treatment follows the molecular characteristics of the disease which have led to the recognition of breast cancer representing a multitude of different biological entities according to hormone receptor status as well as the overexpression of HER-2/neu. These tumor growth-inducing variables can be influenced in a targeted way by a variety of different compounds. With antiendocrine treatment representing one of the first targeted modalities in the history of medicine, antiendocrine treatment still represents a major mainstay of systemic therapy in endocrine-dependent disease. However, the high variability of endocrine receptors relative to the disease course makes the reassessment of endocrine dependence during the course of the disease mandatory. The overexpression of HER-2/neu follows a similar rationale albeit by different means. These have enormously developed during the very recent years and have expanded the previously available option of trastuzumab into a variety of different treatment strategies including pertuzumab which inhibits the hetero- dimerisation of HER-2 with HER-3 as well as the targeted delivery of the cytotoxic compound Maytansine by its coupling to trastuzumab thus resulting in significantly better results than the combination of trastuzumab with capecitabine in the first-line treatment of HER-2/neu overexpressing disease (1).

Angiogenesis represents another treatment option in the biological armentarium of breast cancer including not only bevacizumab which continues to be registered for the use in metastatic breast cancer in Europe, but has also shown to result in a reproducible benefit in patients with breast cancer depending on the combination cytotoxic compound, as in the recently presented TURANDOT trial (2). However, antiangiogenic measures have also shown to further ameliorate antiendocrine treatment as in the case of everolimus when administered in combination with exemestane (3). Angiogenesis, in summary, seems to still have present potential in the treatment of metastatic breast cancer and has to be watched in the further therapeutic context.

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Finally, also cytotoxic drugs – although reprresenting a minority in recent developments – have to be mentioned in the context of recently developed compounds: Thus, not only nab-Paclitaxel, but also Eribulin have been introduced into the treatment of metastatic breast cancer repre-senting a widening of the taxane-based armentarium in the treatment of metastatic breast cancer with the significant fulfilment of study endpoints.

In summary, advanced breast cancer represents an impressive entity demonstrating the validity of the the concept of targeted treatment, but also beyond by reaching into further biologically re levant and valid mechanisms.

References: (1) S. Verma et al., N Engl J Med 2012; (2) C. Zielinski et al., ESMO 2012;(3) J. Baselga et al., N Engl J Med 2012






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12:20 – 12:40 Is there a role for interventional therapies in localized breast cancer?

Stefan O.R. Pfleiderer, MD, EBIRPD Dr. med. habil., Chairman of Radiology

Head of the Department of Radiology, Interventional Radiology, Neuroradiology and Nuclear medicineKlinikum Bremerhaven-Reinkenheide (Germany)

Introduction: Breast cancer is a major health problem and it is the most common cancer in women in the industrialized countries. Up to now, breast conserving surgery followed by irradiation and probably chemotherapy dependent on the lymph node status and the tumor stage is still the gold standard in the treatment of breast cancer. On the other hand, breast conserving therapy has developed to less invasive methods during the last years. Therefore, several minimally invasive procedures in the treatment of breast cancer are under investigation.

Method: Procedures such as interstitial laser therapy, radiofrequency ablation, high focused ultra-sound and microwave ablation are destroying the tumor by heating. In contrast, cryotherapy ablates tumor tissue by cooling down a cryo probe to temperatures as low as -180° C. MRI of the breast tumors prior to ablation is very helpful because MRI is the imaging modality which shows the size of breast tumor most exactly and thus, enables exact planning of the minimally invasive procedure. In most studies, the extent of tumor destruction was evaluated by subsequent surgery and histological assessment of tumor margins.

Result: All reports show partial destruction of the cancers in various extents. Limitations in local tumor control are still a limitation of almost all published studies. The extent of tumor de-struction correlates mainly to tumor size. Most studies are dealing with breast cancers stage Ia and Ib. There are only very few series which showed complete tumor destruction in can-cers with diameters ≤ 2 cm. With larger tumors incomplete ablation occurs much more frequently.

Conclusion: It was demonstrated that thermal therapies are very promising in the treatment of breast cancer. Problems in local tumor control were still the major limitations. On the other hand, even after breast conserving surgery positive margins, which were not apparent on the acute perioperative histology, occurred and may result in local cancer recurrence. Long term results after percutaneous ablation are not available yet. Thus, further studies especially without subsequent surgery but with adjuvant therapy regimens including radiotherapy and chemotherapy according to the state-of-the-art after breast conserving surgery have to be carried out with larger patient series.






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14:10 – 14:30 Neuroendocrine tumors of the GI-tract

Prof. Andrea Tannapfel

Director of the Institute of Pathology Ruhr-University Hospital, Bochum (Germany)

Neuroendocrine tumours of the gastroenteropancreatic tract (GEP-NETs) encompass a heterogeneous group of neoplasms, deriving from neuroendocrine cells through out the gastrointestinal tract. The most common localisation of the primary lesion is within the gastric mucosa, the small and large intestine, the rectum or the pancreas. The clinically heterogeneous GEP-NETs share common biochemical features, with immunoreactivity for the so called ‘pan-neuroendocrine’ markers, including synaptophysin and chromogranin A as well as neurone-specific enolase (NSE). The proliferation potential should be evaluated by staining with the proliferation marker Ki-67 (MIB-I). Functional tumors (with a hormo-nal syndrome), and nonfunctioning tumors could be identified serologically. To predict the clinical behavior of GEP-NET, these tumors are classified on the basis of their clinicopatho-logical features, including localization, size, histological differentiation, proliferative activity (according to Ki67 [MIB-1], local invasion, angioinvasion, and finally metastases, into neo-plasms with benign, uncertain, low-grade malignant and high-grade malignant behavior. A new TNM classification system was invented to get insights in the stage and also prognosis of these heterogeneous diseases.


14:30 – 14:50 Surgery of liver metastasis from neuroendocrine tumors

Prof. Peter Goretzki

Head of the Department of SurgeryStädt. Kliniken Neuss Lukas Krankenhaus GmbH (Germany)

Liver metastases from neuroendocrine tumors are often multiple, distributed to both liver lobes and often diagnosed synchronous with the primary tumor. Comparing this with our experience in patients with liver metastases from primary colon cancers one would question, whether these NEN liver metastases can be treated by local ablative therapy sufficiently at all or whether systemic treatment is needed, principally.Trying to answer this question we compared our own experience with that of the recent literature.Of 205 NEN patients treated at the surgical department of LkNe during the last 10 years 70 patients had pancreatogenous hypoglycemia (insulinoma-NSIPHS) with no malignancy. Of 53 patients with other pancreatic NEN and 51 patients with small bowl NEN 61 (59%) had synchronous (n=42) or metachronous (n=19) liver metastases. In additional 18 of 27 patients (67%) with gastrointestinal or unknown primary tumor location liver metastases were dem-onstrated.Local radical R0 resection of primary tumour and liver metastases was possible in 16 of 79 patients (20%) and partial (80-90%) resection in 12 (15%). Of these 28 patients 2 died within 90 days after surgery (1 pulmonary embolism, 1 progressive disease) and 2 during the mean follow-up of 6years (progressive disease) (actual survival at 6years 86%).The other 51 patients with liver metastases from NEN demonstrated multiple and bilobar metastatic spread, with no indication for surgical liver resection. The overall survival in these patients was 35/51 (69%) at 6 years.

GEPNET Chair: K. Öberg (Uppsala) / A. Bockisch (Essen)

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Of the fifty patients alive with persistent (n=44) or recurrent (n=6) liver metastases 24 (48%) are tretated by repeated local ablative therapy (TAE) and 26 (52%) by systemic and local or only systemic therapy.Our experience in NEN patients with liver metastases parallels that of the present literature, demonstrating that the majority of NEN patients with liver metastases suffer from multiple and bilobar tumor spread that advocats a combined local ablative and systemic control of the NEN-disease. (Touzios et al Ann Surg 2005, Osborne et al Ann Surg Oncol 2006, Bilimoria et al Ann Surg 2008, Kleine et al Br.J.Surg. 2012, Krampitz et al Arch Surg 2012)

Conclusion: Only a minority of patients with neuroendocrine tumors (NEN) and hepatic metastases shows regional restricted hepatic disease. In these patients, however, surgery is advocated and promises improved survival, when compared to patients with diffuse and bilobar NEN metastases.






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14:50 – 15:10 Intra-arterial therapies: SIRT or TACE?

Prof. Thierry J. de Baère

Head of the Department of Interventional RadiologyInstitut Gustave Roussy, Villejuif (France)

Liver is often the primary site of metatases for Gastro-Entero-Pancreatic (GEP) neuroendo-crine tumors (NET) of grade 1/2, and liver remains the predominant site of disease for a prolonged period of time in many patients. Liver involvement is responsible for symptoms such as carcinoid syndrom in a large proportion of patients. Due to this preferential location and symptoms, intra-arterial therapies are proposed in symptomatic patients, patients with progressive liver disease, or patients with a high tumor load. Due to the recent advanced in Targeted therapy, intra-arterial therapy are proposed early for intestinal NET than for pan-creatic NET.

TACE and TACE demonstrated objective response in 80-92% of patient in recent studies, and symptoms control in close to 90% of cases. TACE and TAE demonstrated 5years survival of 53-83%, and 40-67% respectively, but whether TACE or TAE impact on survival has yet to be demonstrated. Respective benefit of TAE vs TACE, and of different regimen of TACE includ-ing various drugs, or drug carrier remains uncertain. TACE seems to have demonstrated a benefit in response rate over TAE in PNET, while this benefit is controversial in enteric NET. Streptozotocin have been used by some centers with benefit in response rate over doxoru-bicin. Drug eluting beads have demonstrated high rate of tumor response but some added toxicity when compared with the lipiodol-TACE when using large size beads.

Radioembolization seems very well tolerated with response rate from of 50-63% and with promising prolong PFS around 18 months. Radioebolization remains interestin as salvage therapy of TACE, and can be performed safely even after systemic therapy with peptide receptor radionucleide therapy.

Arterial phase enhancing tumor, non pancreatic origin, low tumor burden, and first line treat-ment have been demonstrated as prognostic factor of response to intra-arterial therapies. Whipple procedure remains a contra-indication of TACE and TAE and probably of radioem-bolization as well.

According to ENETS consensus guidelines, TACE and TAE are the two techniques recom-mended, while radioembolization is still investigational.

The role of combined therapy including intra-arterial therapy (TACE) and systemic therapy with sunitibib or everolimus is under investigation. Intra-arterial injection of peptide receptor radionucleide has been recently investigate with a possible benefit over IV therapy.

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15:10 – 15:30 Intraarterial therapies or surgery

Prof. Timothy M. Pawlik, MD, MPH, PhD

Director of the Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary ClinicJohns Hopkins Hospital, Baltimore (USA)

Neuroendocrine tumors (NET) are rare neoplasms that encompass a broad spectrum of disease sites and histologies. Although the natural history of many NET is characterized by slow progression and an indolent biology, about 40% of patients with NET will develop meta-stasis during the course of their disease with the liver being the most common site. In a sub-set of patients, neuroendocrine liver metastasis (NELM) can be associated with significant symptoms due to secretion of tumor-related hormones. As such, NELM can affect not only patient survival, but also adversely impact patient quality of life. Systemic chemotherapy has limited success in treating patients with NELM and therefore there is considerable interest in liver-directed therapy. In general, surgical management of NELM remains the only po-tentially curative option for NELM with 5-year survival approaching 60-80%. However, given the high incidence of recurrence following surgery, some investigators have questioned the role of surgical management for NELM. These clinicians have suggested that intra-arterial therapy (IAT) may be better suited as the primary therapy for NELM. In most instances, IAT consists of transcatheter arterial chemo-embolization (TACE), bland transarterial emboliza-tion (TAE), Drug-Eluting Beads (DEB), or Yttrium-90 (Y-90). IAT has been shown to be effective in retarding tumor progression, as well as palliating symptoms related to NELM. Direct com-parisons of surgical and IAT patients to assess the comparative efficacy of these treatments is not appropriate as these patients have disparate patient characteristics. When patients are matched using propensity score methodology to examine as homogenous a cohort of patients as possible, a significant effect of symptoms and disease burden on outcome relative to receipt of surgery versus IAT is noted. Data suggest that surgical management of hepatic NET metastasis benefit most those patients with low volume (< 25%) disease or those with symptomatic, high volume disease. In contrast, asymptomatic patients with a large (>25%) burden of liver disease who underwent surgical management have no discernible difference in long-term outcome compared with IAT. As such, surgical management of NELM should be reserved for patients with a low systemic burden of disease and low-volume hepatic disease or for those patients with symptomatic high-volume disease. In contrast, patients with a high burden of intrahepatic disease, especially those with asymptomatic disease, are probably best served with loco-regional IAT rather than surgical debulking.

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15:30 – 15:50 Molecular imaging (Gallium-68 SMS-Receptor PET/CT) and Peptide Receptor Radionuclide Therapy (PRRNT) of GEP-NEUROENDOCRINE NEOPLASMS (GEP-NEP)

Prof. Richard Paul Baum

Head of Department for Molecular RadiotherapyENETS Center of ExcellenceZentralklinik Bad Berka (Germany)

68Gallium is a positron emitter (T1/2 68 min) and can be produced from a generator in a convenient, “in-house” preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7,000 68Ga PET/CT studies in patients with NEP and have estab-lished SSTR PET/CT as the new gold standard for imaging G1 and G2 NEP (staging, restaging, therapy response evaluation and detection of unknown primary NEP).

The same SSTR targeting peptides can be labeled with 177Lutetium or 90Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective treatment for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advan-tage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NEP was 39 mo. Similar results were obtained for NEP of unknown primary (median PFS: 38 mo) whereas NEP of small bowel had a median PFS of 51 months. Side ef-fects like grade 3-4 nephro- or hematotoxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NEP, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity, given over a longer period of time (Bad Berka Concept using se-quential (DUO) PRRNT) results in excellent therapeutic responses. By this approach, severe hematological and/or renal toxicity can be avoided and quality of life/clinical symptoms can be significantly improved.






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15:50 – 16:10 Modern systemic therapy of neuroendocrine tumors in 2013

Prof. Kjell Öberg, MD, Ph.D.

Chairman Centre of Excellence Endocrine TumorsUniversity Hospital Uppsala (Sweden)

Neuroendocrine tumors (NETs) of the gastrointestinal tract constitute a heterogeneous group of malignancies with various clinical presentation, tumor biology and progression of the disease. The new WHO-classification system has tried to classify the various subtypes into three categories; Neuroendocrine tumor NET-G1, G2 and NEC-G3. The first group are tumors with low prolife-ration and well-differentiated histopathology, Ki-67 <2%, NET-G2 Ki-67 between 2-20% and NEC-G3 Ki-67 >20%. This grading system forms the basis for a modern systemic treatment of various NETs, but of course also tumor stage and localisation as well as the patient’s general condition play a role. For patients with NET-G1 the standard treatment consists of somato-statin analogs, both for symptom and tumor control. For selected patients it can also be alpha interferon or a combination of both. Recent studies have also indicated a role of everolimus in NET-G1. NET-G2, mostly pancreatic NETs, are treated according to the ENETS guidelines by chemotherapies, such as streptozotocin plus 5FU/doxorubicin, but since two new targeted agents, everolimus and sunitinib, has been registered world-wide for pancreatic NETs G2 it can be discussed whether these new agents should be first-line therapy instead of chemo. NET-G3 is still subjected to treatment with cisplatinum plus etoposide as first-line, but also temozolomide plus capecitabine or bevacizumab are also an alternative for this type of high proliferating tumors. Temozolomide plus capecitabine has also been considered as a valid first- or second-line treatment for NET-G2.

ConclusionToday the systemic medical treatment of NETs has been significantly enlarged by the inclu-sion of new targeted agents, such as tyrosine kinase and mTOR-inhibitors. The precise role of these new agents in the treatment algorithm has to be further analysed in prospective randomized trials and also based on information about specific tumor biology for the differ-ent subtypes of NETs.

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09:00 – 09:20 Resection of colorectal liver metastases

Prof. Graeme Poston , MB BS, MS, FRCS(Eng), FRCS(Ed)

Department of Liver SurgeryAnintree University Hospitals Liverpool (United Kingdom)

Ten years ago, the definition of respectability of colorectal liver metastases (CLM) was no more than 3 metachronously detected, unilobar metastases, no greater than 5 cm in size, CEA <100 and resectable with at least a 1 cm margin of healthy liver tissue. As such <10% of patients with liver limited disease were considered for hepatectomy, with a 40% 5 year sur-vival, so overall 5 year survival in stage 4 disease was 4%.

A meta-analysis in 20061 of all prospectively collected large single centre series published 1990-2000 and recently updated in a similar analysis covering 200-20112. These data include outcomes on >25,000 hepatectomies for CLM. We have also published data on >13,000 pa-tients registered on the LiverMetSurvey Registry3,4. What these data show is that while each of these factors (size, number, metachronous detection, resection margin, CEA level, pres-ence of resectable extra-hepatic disease (EHD), stage and differentiation of primary tumour) all have a negative impact on overall survival, none increases the hazard ration to >2, there-fore their influence(even when combined) is relative and not absolute.

Furthermore, recent advances in surgical technique, pre-operative portal vein embolisation, two stage hepatectomy, caval isolation and caval resection, combined with advances in induc-tion and neoadjuvant chemotherapy, have more than doubled the number of patients now considered resectable by our new criteria.

Therefore the definition of resectability of CLM in 2013 is determined by how much disease free liver can be preserved in a patient considered technically resectable. Most experienced centres consider the preservation of 25-30% viable (good vasculo-biliary inflow and outflow) future remnant liver as sufficient to proceed with hepatectomy with curative/long-term sur-vival intent. As such nearly 40% of patients with CLM (+ those with resectable EHD) are now considered candidates for liver resection5. However, it is also clear that such decisions can only be made by experienced Hepatobiliary surgeons working in dedicated tertiary Hepatobil-iary centres and not left to inexperienced general surgeons or general oncologists6, 7.

1 Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published series. Simmonds P et al. Br J Cancer 2006; 94: 982-992 Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Kanas GP et al. Clin Edpidemiology 2012; 4: 1-193 Liver resection of colorectal metastases in elderly patients: is it worthwhile and is there and age limit? Adam R et al. Brit J Surg 2010; 97: 366-764 Is perioperative chemotherapy useful for solitary, metachronous colorectal liver metastases. Adam R et al. Annals Surgery 2010; 252: 774-875 The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus. Adam R et al. Oncologist. 2012; 17: 1225-396 Surgical management and outcomes of colorectal cancer liver metastases . Morris EJA et al. Brit J Surg 2010; 97: 1110-87 Effect of specialist decision-making on treatment strategies for colorectal liver metastases. Jones RP et al. Br J Surg. 2012 Sep; 99(9):1263-9.

COLORECTAL CARCINOMA Chair: H.-J. Meyer (Hannover) / P. Pereira (Heilbronn)

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09:20 – 09:40 Resection or ablation

Dr. Warner Prevoo

Department of RadiologyHet Nederlands Kanker Instituut Amsterdam (Netherlands)

The golden standard to treat liver metastases from colorectal carcinoma (CRLM) is surgical resection. Is there any indication that one should consider a local minimal invasive treatment instead of surgical treatment? The course of systemic metastatic disease however is that sooner or later recurrence to the liver is very likely. So why do more damage to the liver if a minimal less invasive image guided easy to repeat method is available? Maybe we should consider not to operate in patients especially in cases with a high chance of recurrence. And maybe only chose for repeated ablative treatment sessions?

It is still very difficult to compare different treatment methods in prospective studies. In literature there are no comparative studies to be found.

But what really happens in daily practice? What choices do we make?


09:40 – 10:00 Neoadjuvant treatment of liver metastases

Prof. Claus-Henning Köhne

Head of Department of the Department of Oncology and HematologyKlinikum Oldenburg gGmbH, Oldenburg (Germany)

If respectable, patients with colorectal liver metastases have a curative chance in about 30-40%. Therefore 60-70% of patients will have a recurrence either within the liver or extra hepatic. Data on adjuvant treatment after resection is rare and the number of pa-tients included into those studies low. While a progression free survival prolongation is suggested in these studies no overall survival benefit was demonstrated. It is for this reason that a neoadjuvant approach was studied in the large EORTC EPOC study and pa-tients where randomized to receive FOLFOX followed by surgery or surgery alone. This trial demonstrated a progression free survival advantage for those patients who received neoadjuvant Folfox followed by adjuvant Folfox.

In patients with unresectable colorectal metastases confined to the liver or lung intensive che-motherapy is used in order to downsize the metastases to render them resectable. In centres with an experienced multidisciplinary team about 30-40% of patients become resect-able follow-ing neoadjuvant chemotherapy.

The more efficacious a regimen is, the more likely will patients have a R0-resection. Resecta-bility of liver metastases may therefore be considered as an endpoint in clinical trials. Expe-rienced liver surgeons appear to estimate resectability with a very similar outcome.

Conclusions:Neoadjuvant chemotherapy is a useful tool in patients with resectable liver metastases and is mandatory for those with unresectable liver metastases.

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10:20 – 10:40 Hepatic arterial infusion of colorectal liver metastases

Prof. Nancy Kemeny

Gastrointestinal Oncology ServiceMemorial Sloan Kettering Hospital New York (USA)

New chemotherapeutic and molecular targeted agents have improved the treatment of color-ectal cancer, increasing response rates to 40-60% and survival to 20-24 months.

For patients (pts) with unresectable liver metastases, in a randomized study using HAI (FUDR/Dex) compared to systemic FU/LV, the median survival was 24.4 vs 20 months, (p 0.0034), respectively. Survival has increased further with the addition of systemic therapy to HAI. Us-ing systemic irinotecan+Oxaliplatin with HAI-FUDR/ Dex, the response rate was 91% with a median survival of 41 months, allowing 49% of initially unresectable patients to undergo liver resection. The chance of getting an unresectable pt. to resection is listed below.

Unresectable Disease-Preop Treatment

# of Patients Resected Med. Survival (Mos) Why Unresectable

Folfox 178 12% 20 45% 6 or more lesionsFolfox 42 40% 26

Folfiri 40 33% - 61%>6 mets or size

Folfoxiri 74 26% 36.8 85% >4 or size

HAI+Systemic 105 57% 51 Diffuse bilateral disease where resection would require resection of both 3 portal veins or 3 hepatic veins.

Chemo Naïve 44

Previously Treated

63* 44% 32

HAI-oxali 69* 24% - Massive liver involvement

*Previously Treated


10:00 – 10:20 Portal vein embolization or radiation lobectomy

Prof. Riad Salem

Director of Interventional Oncology in the Department of RadiologyNorthwestern University Chicago (USA)

The majority of HCCs are not resectable. One of the reasons involves the presence of a small future liver remnant. The mainstay approach to inducing hypertrophy of the liver remnant is with portal vein embolization (PVE). Radiation lobectomy with Y90 is a novel method of achieving the same (or better) results when compared with PVE. The advantage of this tech-nique is that is it: 1) treats the underlying cancer, 2) causes high rates of future liver remnant hypertrophy and, 3) embeds a biologic test of time prior to consideration of resection. This presentation will highlight the outcomes of patients undergoing Y90 with the intent of causing contralateral hypertrophy prior to resection. Outcomes will be compared with PVE.






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Adjuvant Therapy After Liver ResectionThe most effective treatment for liver metastases is surgical resection; however, 75% of these patients will recur mostly in the liver. Results of 4 large randomized studies comparing HAI to systemic, demonstrated significant increase in recurrance free survival in 3 of 4 randomized studies. New trials at MSKCC on more than 100 patients show 4-year survival of 80% after liver resection when adjuvant HAI plus SYS used.

5-Year Disease Free Survival

Studies #Pts HAI SYS P value

MSKCC 156 55 30 .02

ECOG 75 40 20* .03

Lygidakis 122 60 35 .0002

Lorenz 186+ 20 12.6* NS

*No treatment in control arm+treated patients

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10:40 – 11:00 Combination of TACE with systemic therapies: Where are we now?

Prof. Robert C. G. Martin

Director of the Division of Surgical OncologyUniversity of Louisville (USA)

Purpose To evaluate the effectiveness of drug-eluting beads loaded with irinotecan (DEBIRI) with con-current chemotherapy in the treatment of hepatic malignancies.

Materials and MethodsA total of 267 patients were enrolled in a prospective, open-label, multicenter, multi-national, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). 60 of these patients received concurrent chemotherapy treatment. Complications were graded by Cancer Therapy Evaluation Program’s Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included.

ResultsOf those that did not receive concurrent chemotherapy, a total of 207 patients received 364 DEBIRI treatments and 29 doxorubicin treatments (range 1-8 per patient). Of the patients that received concurrent chemotherapy (Xeloda, Erbitux, or another type of chemotherapy), 60 pa-tients received 114 DEBIRI treatments and 8 doxorubicin treatments (range 1-8 per patient). Multivariate analysis identified concurrent chemotherapy with DEBIRI or DEBDOX as more effective for liver dominant therapy colorectal liver metastatis for response and progression free survival.

ConclusionsDEBIRI treatments have a lower rate of complication when given with concurrent chemotherapy in the treatment of hepatic malignancies. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.






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11:20 – 11:40 Combination of SIRT with systemic therapies: Where are we now?

Dr. Harpreet Wasan

Consultant & Reader in (Medical) OncologyDepartment of Cancer MedicineHammersmith Hospital, London (United Kingdom)

Metastatic Colorectal cancer (mCRC) remains a leading cause of cancer-related death. Advances in chemotherapy strategies and surgery, resulted in significant improvement in 5-year overall survival (OS) in the last 2 decades. Emerging new predictive and prognos-tic factors are increasingly informing the personalised management of mCRC, including: clinical subsets (i.e. liver-only disease) and molecular markers (i.e. KRAS and BRAF status). Thus mCRC treatment is rapidly advancing to specifically tailored treatment strategies. The ultimate aims are to increase survival rates and improve quality of life. There is strong evi-dence that down-staging of liver metastases for curative resection delivers the best long-term prognosis. There is increasing evidence that effective reduction of the total tumour burden in the liver may also prolong survival and complement chemotherapeutic approaches. This will be discussed, focusing on the emerging clinical evidence of loco-regional liver treatments, including radioembolisation with yttrium- 90 [90Y] resin microspheres (SIR-Spheres) with standard-of-care chemotherapy, where trials have now established safety. In the chemo-refractory salvage setting, radioembolisation is now one of the few remaining options with clinical effectiveness data, including a randomised trial. There is evidence of extremely high response rates in earlier settings and the challenge now is how best to safely integrate non-chemotherapeutic approaches into the current mCRC treatment paradigm. Two phase III studies, (international multi-centre randomized controlled trial [SIRFLOX] and the UK [FOX-FIRE]) are close to completion.






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11:40 – 12:00 Unresectable CRLM in 2013: For whom and when can interventional therapies be recommended in the light of modern drug therapies

Prof. Dirk Arnold

Director of the Clinic for Medical OncologyTumor Biology Center Freiburg (Germany)

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Editor and responsible for the editorial content:Dr. med. Stefan PluntkeConsultant in Interventional OncologyKliniken Essen MitteEvang. Huyssens-Stiftung / Knappschaft GmbHHenricistr. 9245136 Essen

Design Concept:networkJuliane Stahr Schmargendorfer Str. 612159 Berlin

Cover Graphic:© ag visuell – Fotolia

Print:Neumann Druck OHGBenzstraße 184030 Landshut

All Content: Status at the time of printing, March 2013






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