Pamplona, junio de Futuro de la Hepatología: Cáncer Hepático. Bruno Sangro Clínica Universidad de Navarra. IDISNA. CIBERehd.

Transcription

1 Pamplona, junio de 2008 Futuro de la Hepatología: Cáncer Hepático Bruno Sangro Clínica Universidad de Navarra. IDISNA. CIBERehd. Pamplona, Spain

2 Etiología del Cáncer Hepático HBV HCV Alcohol NAFLD Iron Dis. Obesity Diabetes Smoking Cirrhosis Female Sex Coffee HCC Mixed HCC- icca Other malignant tumors icca Obesity Diabetes Alcohol PSC Flukes Hepatholithiasis Hepatotoxins Cirrhosis NAFLD HBV HCV

3 Actividades Propias del Hepatólogo Diagnóstico Tratamiento M.A.P. M.I. Cirujano Hepático Oncólogo Médico Hepatológo Hepatólogo Pediatra Digestivo Radiólogo Intervenc.

4 HCC: > 850,000 new cases annually worldwide. Epidemiology of HCC

5

6 Increasing Incidence of Liver Tumors Changes in age standardized mortality rate HCC icc

7 Pathogenesis of HCC

8 Genetic variation and risk of cancer RISK FACTORS Cancer Patients Normal Individuals GENETIC DIFFERENCES

9 Overuse of Non- Invasive Criteria in Liver Tumors T1 T2 DWI arterial portal venous

10 Overuse of Non- Invasive Criteria in Liver Tumors

11 Tumor Markers AFP has significant overlap with cirrhosis without HCC has low sensitivity and specificity is not valid for evaluation of response CA 19-9 has significant overlap with benign diseases. has low sensitivity and specificity (62% and 63%, respectively). bile duct obstruction may affect CA 19-9

12 Okuda Classification of HCC (1985) Surgical Non- Surgical Okuda K, et al. Cancer 1985; 56:918

13 Therapeutic Procedures for HCC Liver Transplantation Liver Resection Percutaneous Ablation Chemoembolization Radioembolization EBRT Systemic Therapies Varela M, et al. Med Clin (Barc)

14 Guidelines in 2020

15 Comparisons Between Different Treatment Options Level of Evidence LT RES TACE RE SOR BSC/Pl LT RES 2 TACE 2 RE

16 Expected Outcomes in HCC Patients Patient and Tumor Characteristics Comorbidities Outcome Treatment Characteristics Treatment Performance

17 Driving Forces in HCC Treatment Main Problem

18 Driving Forces in Liver Transplantation Organ Shortage: Marginal donors LDLT HCV therapy Organ shortage Target Population: Downstaging Expanded criteria Ab initio More loose criteria may apply to LDLT What recurrence rate is acceptable for donors? Response to downstaging therapy and progression within accepted criteria while on the waiting list may prove as stress test (but yet weak scientific evidence)

19 Driving Forces in Liver Resection Morbidity & Mortality Laparoscopic resection Increase liver reserve Availability Functional FLR Target Population: Downstaging Intermediate Stage Portal Hypertension

20 Driving Forces in Percutaneous Ablation destructive ability technology development Early Diagnosis Target Population: screening programs Ethanol, acetic acid, hot saline Radiofrequency, microwave, laser Cryotheraphy High- intensity focal ultrasound (HIFU) Irreversible Electroporation (IRE) Oncolytic viruses

21 Driving Forces in Transarterial Therapies Morbidity Smaller beads Traceable particles More efficient agents Predictability Reproducibility Target Population Adjuvant effect Ablation TACE Series (ILCA, EASL, ASCO 2014) Author, Country Stage n 5- year Survival Triolo, Italy BCLC- A 44 71% Wang, Taiwan BCLC- A % Chen, China Milan % Terzi, Italy BCLC- A % Triolo, Italy BCLC- B 37 42% Wang, Taiwan BCLC- B %

22 Driving Forces in Systemic Therapies Loose & changing paradigm Increased toxicities Lack of predictive tools Molecular Biology Target Population Combination Regimes Combination with LRT Adjuvant effect First line (sorafenib naïve): Sorafenib + Erlotinib vs. Sorafenib Sorafenib + Doxo vs. Doxo Sorafenib vs. Brivanib Sorafenib vs. Sunitinib Sorafenib vs. Linifanib Sorafenib vs. Y90 Sorafenib + Y90 vs. Sorafenib Sorafenib vs. Lenvatinib Sorafenib vs. Nivolumab Second line (sorafenib resistant/intolerant): Brivanib vs. Placebo Everolimus vs. Placebo Tivantinib vs. Placebo (c- met high) Ramucirumab vs. Placebo Ramucirumab vs. Placebo (AFP high) Regorafenib vs. Placebo Nivolumab

23 Molecular Drivers of HCC and icc no clear oncogenic addiction loops reporting response to targeted therapies have been described in HCC or icc

24 Biological Features of the Intermediate Stage Molecular Classification Very Early and Early Stages Intermediate and Advanced Stages Non- Invasive Diagnosis Diagnostic Biopsy Non- Invasive Diagnosis Surgery Ablation Intraarterial Systemic Histological Confirmation

25 Driving Forces in Systemic Therapies Loose & changing paradigm Increased toxicities Lack of predictive tools Molecular Biology Target Population Combination Regimes Combination with LRT Adjuvant effect

26 Sequencing Systemic Agents in HCC SORAFENIB REGORAFENIB NIVOLUMAB TACE TARE SORAFENIB NIVOLUMAB REGORAFENIB LENVATINIB NIVOLUMAB SORAFENIB NIVOLUMAB SORAFENIB REGORAFENIB NIVOLUMAB SORAFENIB LENVATINIB REGORAFENIB TACE / TARE NIVOLUMAB SORAFENIB REGORAFENIB

27 Driving Forces in Systemic Therapies Loose & changing paradigm Increased toxicities Lack of predictive tools Molecular Biology Target Population Combination Regimes Combination with LRT Adjuvant effect Phase Target Agents 1/2 PD- 1 + c- met PDR001 vs PDR001 + Capmatinib 1/2 PD- 1 + pleiotropic pathway modifier Nivolumab + CC /2 PD- 1 + TGFb Nivolumab + Galunisertib 1a/b CTLA4 + VEGFR2 Durvalumab + Ramucirumab 1b PD- 1 + multikinase Pembrolizumab + Nintendanib 1 PD- 1 + multikinase Pembrolizumab + Lenvatinib 1b PD- 1 + multikinase PDR001 vs PDR001 + Sorafenib 1/2a PD- 1 + oncolytic virus Nivolumab + Pexavec

28 Intermediate stage: A grey zone LT Child Pugh class B A 0 RE S SIRT TACE SIRTSOR Intermediate Stage

29 Actividades Propias del Hepatólogo Diagnóstico Tratamiento M.A.P. M.I. Cirujano Hepático Oncólogo Médico Hepatológo Hepatólogo Pediatra Digestivo Radiólogo Intervenc.