Percutaneous ablation: indications, techniques and results Giovan Giuseppe Di Costanzo Dipartimento dei Trapianti UOSC Epatologia AORN A Cardarelli - Napoli
Treatment algorithm EASL, EORTC guidelines HCC Stage 0 PS 0, Child Pugh A Stage A C PS 0 2, Child Pugh A B Stage D PS > 2, Child Pugh C Very early stage (0) 1 HCC < 2 cm Carcinoma in situ Early stage (A) 1 HCC or 3 nodules < 3 cm, PS 0 Intermediate stage (B) Multinodular, PS 0 Advanced stage (C) Portal invasion, N1, M1, PS 1 2 End stage (D) 1 HCC Portal pressure/ bilirubin Increased 3 nodules 3 cm Associated diseases Normal No Yes Resection Liver transplantation PEI/RFA TACE sorafenib BSC Curative treatments (30%) Target: 20% Target: 40% Target: 10% 5-year survival (40 70%) OS: 20 mo (45-14) OS: 11 mo (6-14) OS: <3 mo PS, performance status; TACE, transarterial chemoembolization; BSC, Best Supportive Care EASL EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908 943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
Treatment algorithm EASL, EORTC guidelines HCC Stage 0 PS 0, Child Pugh A Stage A C PS 0 2, Child Pugh A B Stage D PS > 2, Child Pugh C Very early stage (0) 1 HCC < 2 cm Carcinoma in situ Early stage (A) 1 HCC or 3 nodules < 3 cm, PS 0 Intermediate stage (B) Multinodular, PS 0 Advanced stage (C) Portal invasion, N1, M1, PS 1 2 End stage (D) 1 HCC Portal pressure/ bilirubin Increased 3 nodules 3 cm Associated diseases Normal No Yes RFA Liver transplantation PEI/RFA TACE sorafenib BSC Curative treatments (30%) Target: 20% Target: 40% Target: 10% 5-year survival (40 70%) OS: 20 mo (45-14) OS: 11 mo (6-14) OS: <3 mo PS, performance status; TACE, transarterial chemoembolization; BSC, Best Supportive Care EASL EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908 943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
AISF expert panel recommendations (1) - For HCC 2 cm, in the setting of a multidisciplinary evaluation, RFTA can be considered the first-line treatment when performed in expert centres - For HCC of 2.1-3 cm,the choice between surgery and RFTA should be made on a case-by-case after a multidisciplinary evaluation - Patients with nodules >3cm should be treated with surgery when feasible
AISF expert panel recommendations (2) - When technically feasible, RFTA should be preferred to PEI due to better efficacy and predictability of treatment result - Response to ablation can be assessed with CEUS, MRI, or CT approximately 1 month after treatment, and every 3-4 months thereafter up to 2 years of follow-up. In this setting, CT or MRI should be performed every 6 months.
Percutaneous ablation a) chemical (PEI, PAI) b) thermal - hyperthermic (RFA, MW, LA) - hypothermic (CRYO)
PERCUTANEOUS ETHANOL INJECTION
Di Costanzo, unpublished PEI: complete ablation according to the size 90 80 70 60 n = 134 50 40 30 20 10 84.8 76.5 54.3 27.3 0 20mm 21-30mm 31-50mm > 50mm
PEI: local recurrence according to the size 30mm = 33% > 30mm = 43% Khan et al, J Hepatol 2000 Koda et al, Cancer 2000
PEI can be used in very selected cases
HYPERTHERMIC ABLATION
Temperature ( C) Effect 42 More susceptible to chemotherapy or radiation 45 Irreversible cellular damage in 30-60 minutes 50-55 Irreversible cellular damage in 4 6 min 60-100 Coagulation of tissue >100 Vaporization and carbonization of tissue
Hyperthermic injury Mechanisms - Direct - Indirect or delayed
Chu et al, Nature Reviews 2014
RFA
LeVeen (Boston Scientific) StarBurst (RITA/AngioDynamics)
17 G cooled-tip electrode with a 3-cm exposed tip
Shiina et al, Gastroenterology 2005
Shiina et al, Gastroenterology 2005
Tumor response Orlando A, AJG 2009
Local recurrence Orlando A, AJG 2009
Overall survival Orlando A, AJG 2009
Complete ablation = 212/218 (97.2%)
Pompili et al, J Hepatol 2013
Pompili et al, J Hepatol 2013
P=0.122
P=0.342
Lencioni, Hepatology 2010
Complications Major complications = 0.6-8.9% (1) Mortality = 0.3% (2) 1: Kudo et al, J Gastroenterol 2004 2: Livraghi et al, Radiology 2003
Heat sink effect Statli, et al; Diagn Interv Radiol 2012
MWA
Simons et al, Radiographics 2005
Main advantages of MWA Faster ablation Higher temperatures Not affected by electrical impedance No or minimal heat sink effect
Brace et al.radiology 2007
Complete ablation rate Chinnaratha, JGH 2016
Major adverse events Chinnaratha, JGH 2016
LA
Echolaser XVG system (ELESTA)
Pacella s technique : flat tip technique introducer sheath : needle 21G (0.8mm) laser source : flat-tip fiber (0.3mm) needle 21 G = 0.8mm optical fiber = 0.3mm laser beam =18mm needle 21G=0.8mm optical fiber=0.3mm 10mm
Laser Ablation (LA) liver ablation technique: different US guidance systems Claudio Maurizio Pacella, Regina Apostolorum Hospital, Rome, Italy Giovan Giuseppe Di Costanzo, Cardarelli Hospital, Naples, Italy
Laser ablation <15mm 15 mm 15 mm >25mm <25mm
CT at 4 weeks
Radiofrequency ablation versus laser ablation for the treatment of small hepatocellular carcinoma in cirrhosis: a randomized controlled trial GG Di Costanzo, R Tortora, G D'Adamo, A Galeota Lanza, F Lampasi, L Addario, M De Luca, F Zanfardino, MT Tartaglione, S Mattera, CM Pacella Liver Unit, Cardarelli Hospital, Napoli, Italy ClinicalTrials.gov identifier: NCT01096914 J Gastroenterol Hepatol, 2015
Complete tumor ablation RFA LA Δ (95% CI) per patient, n (%; 95%CI) 68/70 (97.1; 90.2-99.2) 67/70 (95.7; 88.1-98.5) +1.4%* (-6.0% +9%) per nodule, n (%; 95%CI) 75/77 (97.4; 91.0-99.3) 77/80 (96.3; 89.6-98.7) +1.1%* (-5.7% +8.1%) J Gastroenterol Hepatol, 2015
RFA MWA LA Size of applicators 14-17G 13-16G 21G Intratumoral temperature 60-100 C >100 C >200 C Number of applicators (3 cm) 1 1 4 Procedural time (3 cm) 12 minutes 6 minutes 6 minutes Heat sink effect Yes Rare Rare Grounding pads Yes No No Pacemaker Unsafe Safe Safe Validation Yes 1 small RCT 1 NI RCT
Conclusions - PEI should be used only in very selected cases - RFA is the treatment of choice for patients with single HCC 2 cm - Ablation may provide results comparable to resection in the treatment of single HCC 3 cm occurring in compensated cirrhosis - Microwave and laser ablation may be good alternative to RFA for the treatment of nodules in high-risk location and to overcome the heat sink effect - Percutaneous ablation may cause adverse effects
optimizing tumor ablation OPTIMAL ABLATION BIOLOGY
La terapia locoregionale Giovan Giuseppe Di Costanzo UOSC Epatologia AORN A Cardarelli