Hepatocellular carcinoma: Intra-arterial treatments Irene Bargellini U.O. Radiologia Interventistica Azienda Ospedaliero Universitaria Pisana
IRENE BARGELLINI,MD UO RADIOLOGIA INTERVENTISTICA, AZIENDA OSPEDALIERO UNIVERSITARIA PISANA Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene discussione di farmaci in studio o ad uso off-label
Trans-arterial treatments: the advantages Relatively easy and widely available TACE n.-2011 Bargellini I et al. CVIR 2013
Trans-arterial treatments: the advantages Relatively easy and widely available Minimally invasive
Trans-arterial treatments: the advantages Relatively easy and widely available Minimally invasive Flexible Patients conditions Lesions features
Trans-arterial treatments: the advantages Relatively easy and widely available Minimally invasive Flexible Plenty of choice Bland Embolization Lipiodol-TACE Drug-eluting beads Chemotherapy Radioembolization
Trans-arterial treatments: the advantages Relatively easy and widely available Minimally invasive Flexible Plenty of choice
Trans-arterial treatments: how to choose? Guidelines Efficacy Feasibility Availability Costs (and QoL)
Trans-arterial treatments: how to choose? Guidelines Alejandro Forner, María Reig, Jordi Bruix. The Lancet 2018
TACE guidelines: contraindications ABSOLUTE CONTRAINDICATIONS Decompensated cirrhosis (Child-Pugh B 8) Jaundice Clinical encephalopathy Refractory ascites Hepato-renal syndrome Extensive tumour with massive replacement of both entire lobes Severely reduced portal vein flow (e.g. non-tumoural PV or hepatofugal blood flow) Technical contraindications to hepatic intraarterial treatment (e.g. untreatable arteriovenous fistula) Renal insufficiency (creatinine 2 mg/dl or creatinine clearance <30 ml/min) RELATIVE CONTRAINDICATIONS Comorbidities involving compromised organ function: Active cardiovascular disease Active lung disease Tumour size 10 cm Untreated varices at high risk of bleeding Bile-duct occlusion or incompetent papilla due to stent or surgery Raoul JL et al. Cancer Treat Rev 2011
Trans-arterial treatments: how to choose? Guidelines Efficacy
Treatments efficacy TAE TACE Brown K et al. JCO 2016
Treatments efficacy DEB Lipiodol Lammer et al. CVIR 2010; Golfieri R et al. Brit J of Cancer 2014
Treatments efficacy TACE TARE Salem R et al. Clin Gastroenterol Hepatol. 2013; Kolling FT et al. Liver Int 2015
Treatments efficacy TARE Sorafenib Vilgrain V, Lancet Oncol 2017; Chow PC, J Clin Oncology 35 ASCO 2017
Trans-arterial treatments: how to choose? Guidelines Efficacy Feasibility Availability Costs (and QoL)
Costs and quality of life DEB vs Lipiodol Higher tolerability Lower toxicity Better response in more advanced patients Lammer J et al. Cardiovasc Intervent Radiol 2010
Costs and quality of life DEB vs Lipiodol DEB-TACE was found more cost-effective than ctace when a minimum willingness-to-pay of about 2000 3500/QALY was accepted, mainly depending on shorter in-hospital stay and better quality of life Cucchetti A et al. Dig Liver Dis 2016
Costs and quality of life TACE vs TARE SIRTACE: a randomized multicentre pilot trial of SIRT versus TACE in patients with unresectable HCC N pts N treatments N days TACE 15 3.4 13.8 TARE 13 1 11.6 Kolligs FT et al. Liver Int. 2015; 35: 1715 1721
Costs and quality of life TACE vs TARE Prospective study 29 HCC pts for TARE and 27 HCC pts for TACE Despite the more advanced disease of patients who received 90 Y radioembolization, they had a significantly better QoL, based on social well being (P =.019), functional well-being (P =.031), and embolotherapy-specific scores (P =.018). Salem R et al. Clin Gastroenterol Hepatol. 2013
Costs and quality of life TARE vs Sorafenib Vilgrain V, Lancet Oncol 2017
Costs and quality of life TARE vs Sorafenib Markov Model Simulation Rognoni C et al. Value in Health 2017
Trans-arterial treatments: how to choose? Guidelines THE PATIENT Efficacy Feasibility Availability Costs (and QoL)
Trans-arterial treatments: how to choose? THE PATIENT Stratification Strategy
Trans-arterial treatments: how to choose? THE PATIENT Stratification Strategy
Stratification BCLC B Median OS after TACE: 14-47 months Bolondi L et al; Semin Liver Dis 2012 Kim JH et al; Liver Int 2017
Treatments efficacy in BCLC B Pecorelli A et al; ITA.LI.CA group; Liver Int 2017
Stratification BCLC C Giannini EG et al; ITA.LI.CA group; Hepatology 2017
New prognostic system ITA.LI.CA Farinati F et al. PLOS Med 2016
New prognostic system ITA.LI.CA Farinati F et al. PLOS Med 2016
Stratification PVT Pre-TARE Post-TARE 12 months 3 months
Prognostic score to predict response to TARE in HCC with PVT 32.2 mos 14.9 mos 7.8 mos Spreafico C et al. J Hepatology, in press
Trans-arterial treatments: how to choose? THE PATIENT Stratification Strategy
The evolutionary scenario of HCC in Italy Longer survival as a result of earlier tumor detection, but also multiple treatments that are combined in different ways at different time-points Bucci L et al; ITA.LI.CA study group; Liver Int 2017
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA Sept 2012 TACE March 2013 AFP 5ng/ml 72ng/ml Dec 2013
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA Sept 2012 TACE March 2013 Sor Jan 2014 Severe hypertension and atrial fibrillation
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA TACE Sor Y90 Sept 2012 March 2013 Jan 2014 Feb 2014
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA TACE Sor Y90 Sept 2012 March 2013 Jan 2014 Feb 2014 1 month
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA TACE Sor Y90 Sept 2012 March 2013 Jan 2014 Feb 2014 24 months
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA TACE Sor Y90 TACE Sept 2012 March 2013 Jan 2014 Feb 2014 March 2016
Male, 78 years old Multifactorial cirrhosis (HCV+, alcohol, DM) ECOG PS 0 Child-Pugh A6 2012: HCC (3 cm) in VIII segment MWA TACE Sor Y90 TACE TACE Sept 2012 March 2013 Jan 2014 Feb 2014 March 2016 June 2017
Male, 78 years old What is the best approach NOW? What could we do NEXT? MWA TACE Sor Y90 TACE TACE Sept 2012 March 2013 Jan 2014 Feb 2014 March 2016 June 2017
TACE vs TARE Chemioembolizzazione ischemia Ø 40-1300 μm Ø 20-60 μm Radioembolizzazione radiazione
TARE potential indications in HCC 1. Single tumor infiltrating segmental or lobar portal vein branches (BCLC C) 2. Intermediate stage HCC (BCLC B) with relative contraindications to TACE 3. Progression after TACE or sorafenib Sangro B, J Hepatol 2012
Vascular injuries and parasistic flow after TACE After 3 TACE cycles After combined MWA-TACE
Enrolling BCLC-B patients for TARE Pisa experience March 2012 - Dec 2016 111 HCC pts selected for Y90-33 (29.7%) BCLC-B -78 (70.3%) BCLC-C BCLC B BCLC C 2012 2013 2014 2015 2016 Drop-outs after diagnostic work-up (16.2%) - 11 (33.3%) BCLC-B - 9 (11.5%) BCLC-C Lung shunt n=4 Hepatic decompensation n=2 Slow flow n=2 Parasistic flow n=2 Cholecystites post-emb n=1
TARE as 1 st treatment option in selected bad BCLC B patients 1 year
TACE - when to stop TACE TACE another TACE?
TACE - when to stop Forner A et al. Lancet 2018
TACE - when to stop Conversion to sorafenib significantly improves OS in patients refractory to TACE therapy with intermediate-stage HCC. Orizumi et al. Liver Cancer 2015
TACE - when to stop
To sum up:
..and while research keeps moving on Balloon-occluded TACE (BO-TACE) New particles: Small size Absorbable Radiopaque Loading with new agents: Idarubicin Molecular - targeted
HCC treatment: from 2D Forner A et al. Lancet 2018
HCC treatment: from 2D to 4D?
HCC treatments: from alternatives to complementarities