1) Radiofrequency ablation is recommended as the main ablative therapy for HCC tumors less than 5 cm due to better control of the disease. Ablation and resection may be equivalent for very early and early stage HCC. 2) For HCC less than 5 cm in candidates for surgery, the role of new ablation techniques needs to be defined, tool by tool. Combined treatment (TACE+RF) may help address the difficulty of distant recurrence. 3) DEB-TACE and conventional TACE showed similar efficacy and safety profiles in a randomized controlled trial for intermediate HCC, with less post-procedure pain with DEB-TACE. Optimization of bead size is ongoing.

1. Radiologie Interventionnelle
&
CHC
Thierry de Baère
Imagerie thérapeutique - Gustave Roussy - Villejuif
Journée d’Hépatologie du Centre Hépato-Biliaire
12 juin 2015 - Paris

2. J Hepatol 2012. 56; 908–943. JM. Llovet; R Lencioni; AM. Di Bisceglie; PR. Galle; JF Dufour; TF. Greten; E
Raymond; T Roskams; T de Baere; Michel Ducreux; and Vincenzo Mazzaferro.

3. J Hepatol 2012. 56; 908–943. JM. Llovet; R Lencioni; AM. Di Bisceglie; PR. Galle; JF Dufour; TF. Greten; E
Raymond; T Roskams; T De Baere; Michel Ducreux; and Vincenzo Mazzaferro.

4. %
AP
n=928
EU
n=1113
LA
n=90
USA
n=563
Japan
n=508
Overall
N=3202
All LRTs 67.2 43.5 27.8 49.4 84.4 57.5
TACE 60.3 33.1 13.3 37.1 71.3 47.2
Conventional
Lipiodol TACE * 90.2 59.2 83.3 40.7 82.3 73.9
DEB-TACE *
2.9 36.1 16.7 39.7 1.7 15.9
Ablation 15.5 20.2 17.8 12.6 50.0 22.2
Surgery 24.2 15.5 5.6 9.4 43.3 21.1
* For patients who received TACE: n=1511; AP=560, EU=368, LA=12, USA=209, Japan=362;
AP, Asia-Pacific; LA, Latin America; LRTs, Loco-Regional Therapies
Lencioni R et al. Int J Clin Pract 2014;68:609-617
GIDEON
Pre-Sorafenib therapy in 3202 HCC (observation)

5. Breen DJ,. Nat Rev Clin Oncol 2015;12:175-186
Ablation for Early-Stage HCC:
Italy
Japan
Corea
France

6. Feng K et al. J Hepatol 2012;57:794-802Huang J et al. Ann Surg 2010;252:903-912
● 230 patients, 94% Child A
● Single ≤ 5 cm, up to 3 ≤ 3 cm
● 168 patients, 49% Child A
● Up to 2 HCC tumors ≤ 4 cm
Overall Survival Overall Survival
months months
p = 0.001 (log-rank test) p = 0.342 (log-rank test)
Ablation vs. Resection : Randomized Trials

7. Feng K et al. J Hepatol 2012;57:794-802Huang J et al. Ann Surg 2010;252:903-912
● 230 patients, 94% Child A
● Single ≤ 5 cm, up to 3 ≤ 3 cm
● 168 patients, 49% Child A
● Up to 2 HCC tumors ≤ 4 cm
Overall Survival Overall Survival
months months
p = 0.001 (log-rank test) p = 0.342 (log-rank test)
Ablation vs. Resection : Randomized Trials

8. "Very Early” (stage 0) vs "Early" (stage A) VS “Milan”
Sasaki A et al. Cancer 2005;103:299-306
46% of patients
with single HCC
< 5 cm show
microsatellites
on histology
Radiofrequency ablation is recommended in most instances as the main ablative therapy in
tumours less than 5 cm due to a significantly better control of the disease
(evidence 1iD; recommendation 1A)
J Hepatol 2012. 56; 908–943. JM. Llovet; R Lencioni; AM. Di Bisceglie; PR. Galle; JF Dufour; TF. Greten; E
Raymond; T Roskams; T de Baere; Michel Ducreux; and Vincenzo Mazzaferro.
Milan criteria : X3 <3cm ; >5cm

9. Pompili M et al. J Hepatol 2013;59:89-97
Tumor Recurrence
Overall Survival

10. Ablation in HCC : APASL Consensus
Omata M et al. Hepatol Int 2010;4:439-474
LOCATION!
T

11. Omata M et al. Hepatol Int 2010;4:439-474
Ablation in HCC : APASL Consensus

12. Forner et al. Lancet 2012;379:1245-1255
Ablation Ablation
The Two Roles of Ablation in HCC Treatment:
Updated BCLC Treatment Algorithm

13. Focused Ultrasound Cryoablation
Radiofrequency Ablation
Irreversible Electroporation
Laser AblationMicrowave Ablation

14. Mazzaferro V, Lencioni R, Majno P. Semin Liver Dis 2014;34:415-426
Image-Guided Ablation of HCC:
Evolving Methods and Technologies

15. • Resection et ablation sont probablement équivalente pour
les stade 0 et A (very early; early)
 Complémentaire plus que compétitive : localisation
• Pour les HCC < 5cm si candidat chirurgicaux limites
 Rôle des nouvelles techniques d’ablation à définir , outil par outil
 Traitement combiné (TACE+RF)
• La difficultés est plus celle de la récidive à distance que de
la récidive locale
 Traitement préventif ! (STORM study)
Ablation for Early-Stage HCC

16. BCLC Staging and Treatment Strategy:
Critical Considerations
EASL-EORTC. J Hepatol 2012;56:908-943 - Eur J Cancer 2012;48:599-641

17. BCLC Staging and Treatment Strategy:
Critical Considerations
EASL-EORTC. J Hepatol 2012;56:908-943 - Eur J Cancer 2012;48:599-641
ADVANCED STAGE:
- ECOG PS 1-2
- Portal Vein Invasion
- Extrahepatic Disease

18. (Yau T. Gastroenterology 2014;146:1691–1700 )EVM : extrahe-patic or vascular invasion/metastasis
0 / 1 / 2 negative factor
Tumor size: ≥ 5 cm
Tumor number: ≥ 3
Intrahepatic vascular invasion

19. (Yau T. Gastroenterology 2014;146:1691–1700 )

20. • HKC identified subsets of BCLC B & 50% of BCLCC C
more aggressive treatments than recommended by BCLC
Such aggressive treatments Improved survival outcomes
 hypothetical median OS: HKLC 16.6 months, BCLC 8.9 months)
“The benefits of the HKLC system are clearly apparent when dealing with
patients who have intermediate to advanced stage disease according to
the BCLC”.
“In a European cohort of HCC patients, the newly developed HKLC staging
system does not seem to allow a better predictive value than the BCLC”.
(Adhoute X. J Hepatol 2014)
(Chapiro J. Nat Rev Gastroenterol Hepatol 2014;11:334-336)

21. 177 patients randomized to DEB-TACE or c-TACE (med number of TACE = 2)
• 89 DEB-TACE
• 88 cTACE
(Golfieri R. 2014 BJC; 111 : 255–264)

22. CR
OR
DC
Targeted Overall
(Golfieri R. 2014 BJC; 111 : 255–264)

23. (Golfieri R. 2014 BJC; 111 : 255–264)

24. • Median TTP = 9 months in both arms
• 1- and 2-year survival
 86.2% and 56.8% after DEB-TACE
 83.5% and 55.4% after cTACE (p=0.949).
No difference in AE incidence and severity
except post-TACE pain, more frequent and severe after cTACE (p=0.001).
Pain did not affected the length of hospital stay and patient acceptance of
additional TACEs
(Golfieri R. 2014 BJC; 111 : 255–264)

26. 67 DEB-TACE (53 patients) 100-300 μm (Group 1)
lobar in 42 and selective in 7 cases
65 DEB-TACE (54 patients) 70-150 μm (Group 2)
lobar in 60 and selective in 11
m-RECIST
1-2 months
CR
(%)
PR
(%)
SD
(%)
PD
(%)
Group 1 19 2 67 12
Group 2 16 8 69 7
(Deipolyi AR, J Vasc Interv Radiol 2015; 26:516–522)

27. BCLC Staging and Treatment Strategy:
Critical Considerations
EASL-EORTC. J Hepatol 2012;56:908-943 - Eur J Cancer 2012;48:599-641
Radioembolization
- Sarra
- Soramic
- STOPP HCC

28. A single-centre prospective study of 291 patients with HCC looked
at long-term clinical outcomes with TheraSphere®
Overall response rate according to WHO criteria was 42%
TheraSphere® & HCC
29
Treatment response predicts survival benefit for BCLC A, B &C patients
Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of
long-term outcomes. Gastroenterology 2010;138(1):52–64.

29. (Garlipp B, de Baere T, Seidensticker M. Hepatology 2014.59:1864-1873)
26 matched pairs
PVE : 61.5 ± 39 % after 33 [24-56] days
RE : 29 ± 28 % after 46 [27-79] days (p<0.001)

30. Traitements combinés

31. (Peng ZW; JCO 2013. 31 426-432)
HCC less than 7 cm (single), or X3 & <3cm
TACE-RFA Vs RFA
OS : (HR=0.525; 95% CI = 0.335-0.822; P = .002 )
DFS : (HR=0.575; 95% CI = 0.374-0.897; P = .009)
OS :
treatment allocation (HR=1.87), tum. Size 3cm (HR=1.73),
and tum. number (HR=2.49)
DFS :
Treatment allocation (HR=1.67) and tum. Number (HR=1.97)

32. HR: 0.797
95% Cl: 0.588, 1.08
P = 0.072
Sorafenib
Median: 169 days
95% Cl: 166, 219 days
Placebo
Median: 166 days
95% Cl: 113, 168 days
PrimaryEndpoint Sorafenib 400mg bid
Matching Placebo
R
A
N
D
O
M
I
Z
E
1 3 5 7 9 11 13 15 17 19
TACE
(optional)
Cycle no
(=4 weeks)
n=154
n=153
SPACE Trial

33. PRODIGE 16 - ESSAI FFCD 0905
ESSAI RANDOMISE EN DOUBLE AVEUGLE DE PHASE II-III EVALUANT LA
CHIMIOEMBOLISATION COMBINEE AU SUNITINIB OU A UN PLACEBO CHEZ DES
PATIENTS ATTEINTS DE CARCINOME HEPATOCELLULAIRE (SATURNE)
DEB - TACE with sunitinib 37.5 mg/d orally 4 weeks out of 6 started 7-15 days before TACE for one year vs placebo.
Primary end-point : specific safety of the TACE-sunitinib combination (severe bleeding, liver failure , …)
Secondary end-points : general safety, progression-free survival (PFS), Overall Survival (OS), quality of life.
May 2011 to May 2014 : 78 patients were randomized (39 in each arm)
median age 66 years [IQR (60-70)]. Bilobar HCC : 41 / 70 patients
The median number of cycles was 3 [IQR : 2 :5 ] in arm A and 5 [IQR : 4 :7 ] in arm B
.No bleeding complication; 1liver failure (PT = 40%) armA, & 2 liver failure in arm B (PT=42%, ,encephalopathy).
Sunitinib dose was reduced to 25 mg/d as a result of toxicity for 19 pts (48.7%) in arm A. 6 patients are still under treatment
(3 in each arm). The main grades 3-4 toxicities were: thrombocytopenia (28.2% vs. 2.6% in placebo arm), neutropenia
(28.2% vs. none), asthenia (20.5% vs. 5.3%), diarrhea (5.1% vs. none) respectively in arm A and B. The median PFS in arm
A was 8.8 [95%CI 5.8 -12] months, and 6.3 [95%CI 4.2 - 9.0 ] months in arm B.
Conclusion
This study indicated a modest and manageable toxicity of sunitinib when combined with TACE. Regarding efficacy endpoints
(PFS and OS) we are waiting for more mature data as 6 patients are still under treatment.

34. RFA plus Sorafenib vs RFA Alone in RCC
Hakimé et al, Radiology 2007
4-time increase in ablation volume

35. 125 HCC received TACE
group A (n = 61) : TACE + As2O3 at 10 mg/d for 4 courses (21 days per course)
group B (n = 64) : TACE alone

36. 125 HCC received TACE
group A (n = 61) : TACE + As2O3 at 10 mg/d for 4 courses (21 days per course)
group B (n = 64) : TACE alone

37. J Vasc Interv Radiol 2014; 25:379–387

38. %
EU
n=1113
Overall
N=3202
All LRTs 43.5 57.5
TACE 33.1 47.2
Conventional
Lipiodol TACE * 59.2 73.9
DEB-TACE *
36.1 15.9
Ablation 20.2 22.2
Surgery 15.5 21.1
Conclusion
DOSISPHERES-01
Y-90 GLASS MICROSPHERES FOR HCC :OPTIMIZED DOSIMETRY vs STANDARD DOSIMETRY
STOPP HCC
Y-90 GLASS MICROSPHERES FOR HCC PRIOR TO SORAFENIB THERAPY vs STANDARD DOSIMETRY
Sunitinib loaded beads
Lipiodol ready to inject emulsion