Transcript HCC 2004
Florence ET/ECIO 2008- Terumo/Biocompatible symposium
TACE with DC beads as a pretransplant treatment for HCC Results with anatomopathological data
Pierre GOFFETTE, MD
Interventional Radiology Cliniques Universitaires Saint-Luc Université catholique de Louvain Brussels
Bruix J.,Llovet J.M.: Prognostic Prediction and Treatment Strategy in Hepatocellular Carcinoma
Liver Transplantation for HCC
5 year survival
•
Within Milan criteria
Comparable to overall LT
Waiting time < 6 Mo Drop out % 10-20% No role for pre-LT adjuvant therapy(?) >75%
•
Expanded criteria
(USCF-Mount Sinaï)
(Single tum < 6.5cm or 3 tum < 4.5cm)
25-44%
Belghiti J. Annals Surg Oncology 2008
Liver Transplantation for HCC
•
Main Issues
Dropout rate 30-50% (WT > 6 Mo) Pts beyond inclusion criteria (interm/adv)
•
Rationale for TACE
Bridge therapy Control tumor + prevent progression, vasc. invasion Neoadjuvant therapy to improve survival Downstaging (to fullfil Milan criteria)
Majno P. Ann Surg 1997, Graziadei I. Liver transpl. 2003 Otto G. Liver Transpl. 2006
TACE before LT
Controversial Usefulness
•
Early stages
Effective to prevent tumoral progression
No influence on post-LT (disease-free) survival
•
Intermediate/Advanced stages
Effective downstaging ( > 50% red.) 35-45% Higher post-LT recurrence rate Lower 5 yr survival (41 vs 83%)
Majno P. Ann Surg 1997, Oldhafer K. J. Hepatol 1998 , Graziadei I. L. transpl 2003, Maddala Y. L. transpl 2004, Decaens T. L. Transpl 2005 Llovet J. Sem. Liver Dis 2006, Lesurtel M. Am J Transplantation 2006
HEPATOCELLULARCA
TACE before LT Majno, 1999
Drug Eluting Beads
(DC Beads, Biocompatible UK)
prolonged time
resorbable, and precisely calibrated spheres, able to load the
Without incresead local toxicity
Precise and controlled release of
Decreased serum level of chemotherapeutic agent
the chemotherapeutic agent into the tumor bed.
available sizes
•
27 patients Child-Pugh A
• Response rate (CT at 6 month): 75% • Liver abscesses 2, death 1 • Median follow-up 28 months survival 1 year 92% 2 year 89%
J Hepatology, 2007
Serum doxorubicin pic value (5 min)
Conventional TACE : 890ng/ml Precision TACE : 90ng/ml
J Hepatology, 2007
Brussels Experience
Drug Eluting Beads for HCC before LT Single center study: 18*patients
• •
8
within the Milan criteria
10
outside the Milan criteria Diameter > 5cm > 3 tum < 3cm Multiple tum > 3cm
1 1 8
Downstaging after TACE ?
* overall 73 HCC pts treated by DC beads over a 22 month period
LIVER TRANSPLANT CANDIDATES WITH HCC
CHARACTERISTICS
Sex,
M/F
Age,
years Etiology of Cirrhosis
Ethyl HCV (+ethyl 1) HAV/HBV NASH Primary biliary cirrhosis Non-cirrhotic HCC Serum α-fetoprotein
(ηg/mL)
Child-Pugh classification
(A/B)
Child-Pugh score
15/3 47-73(58) 9 3 2 2 1 1 49 (4,5-3487) 8/10
Mean
7,2
(5-9)
Materials and Methods
HCC Characteristics
•
Distribution
Unilobar Bilobar 10 8
•
Number of nodules
1 (4Pts), 2 (7Pts), 3 (4Pts), >3 (3 pts)
•
Size:
mean 5.5 cm (range 2.1-8.1) • Partial intrahepatic
PV thrombosis
1
Materials and Methods
DC Beads TACE protocol
Lobar(21%)-Segmental/Subsegmental(79%) injection Standardized DC Beads doses and sizes: -
4ml (2 vials) of 300-500 µm particles loaded with 25mg/ml doxorubicin: 100 mg Doxo/session
-
Dilution with 4ml of 320mg% Iodine (ratio 1/1)
Additional unloaded particles (300-500,500-700µ) if persitent flow Prophylactic antibiotherapy
Materials and Methods
DC Beads TACE protocol
• Sequential TACE at 3-5 Mo interval (max 4) • Alternate TACE if bi-lobar lesions • Progressive arterial feeders occlusion (3 Pts) Tace through collaterals (phrenic, int. mam art.) • End-points Primary: Tumor response and Downstaging Secondary: HCC recurrence after LT
Procedural Results
42 sessions in 18 patients
• • •
Mean number of sessions 1(3pts), 2(6pts), 3(8pts), 4(1pt)
•
Serious adverse event Cholecystitis 30-day mortality Transient impaired liver function 2.8
2 0 11 No liver abcess
CT/MRI Follow-up
EASL response after first TACE
• Complete
1
(5,5%) • Partial
Residual peripheral enhancement 7 Persistent enhanced nodules 7
14
(78%) • Stable Disease
3
• Progressive disease
0
• Objective response
15
(83%)
CT/MRI Follow-up
EASL response after last TACE
• Complete
6
(33%) • Partial
Residual peripheral enhancement 6 Persistent enhanced nodules 4
10
(55%) • Stable Disease • Progressive disease • Objective response
1 1 16
(89%)
46 yr old male: Bilobar HCC ( >7cm seg IV)
Downstaging before LT
First TACE session left lobe
46 yr old male: Bilobar HCC ( >7cm seg IV)
Downstaging before LT
Repeated controls CT after first session Second TACE (right lobe) and control CT……waiting list
Patients beyond Milan criteria
Downstaging (10 Pts)
• Sufficient for active LT listing 8 (80%) Partial response 7, complete 1 transplanted
5
• Inadequate 2 (20%) stable disease 1 transplanted
1
(compassionate) progressive disease 1
66 yr old male: 6.5 cm right HCC, 1.8 cm left HCC
Three selective TACE – LT 8 Mo later
T
ACE 1
T
ACE 2
T
ACE 3
66 yr old male: 6.5 cm right HCC, 1.8 cm left HCC
Three selective TACE – LT 8 Mo later
Clinical Outcome (N=18 Pts)
• • •
Transplanted patients 12
Delay: med 8.5 Mo (3-16) Biliary complications: 3 Follow-up: med 8 month
1 recurrence at 4 mo ( < 50% nec)
Patients on waiting list
1 death (pneumonia)
5 Drop out 1
Operative Data
Drawbacks?
•
Complicated arterial anastomosis
Proper Hep. art. occlusion 4 Pedicular inflammation 3 Early arterial occlusion…redo-OLT in 1
7
•
Difficult biliary anastomosis 3
Known Doxorubicin-related complications!
Explanted Specimen after LT(12) / Necropsy(1)
PATHOLOGIC ASSESSMENT All patients
(n=13)
Downstaged Pts (n=6) Recurrence After LT (n=12) Complete
necrosis
OBJECTIVE RESPONSE Partial
necrosis 75% -99%
6 (46%) 6 (46%) 2 3 0/6 0/5 NO RESPONSE Incomplete
Necrosis <70%
1 (8%) 1 1/1
Explanted Specimen
Histological data
• • • •
Complete necrosis of large tumors (> 5 cm) µ-vascular permeation in 1 patient No inflammatory changes Imaging for residual viable tumoral nodules
False (+)
> Atypical regenerative nodule (2 Pts)
False (-)
> untreated hypovascular tumor > very small viable nodules (delayed LT)
52 yr old male, ethyl cirrhosis
5.2 cm right HCC - 2 cm left HCC 3 selective TACE – LT 2 Mo later
52 yr old male, ethyl cirrhosis
5.2 cm right HCC (satellite nodules)-2 cm left HCC MRI: Partial necrosis LT: Remaining viable nodule-µvasc. permeation
56 yr old male: 2 HCC nodules seg III-IV
Three TACE Liver specimen:
No viable tumoral cells
Cyst-like tumoral necrosis
CONCLUSIONS
• Higher anti-tumoral response % if compared with conventional TACE • Complete necrosis could be achieved even in large HCC • TACE-related surgical complications mainly due to Doxorubicin • Effective downstatging of most patients with intermediate-advanced HCC • TACE with DCbeads could reduce the dropout % • Large prospective studies are needed
Drug Eluting Beads vs Microspheres before LT
Nicolini A.F. March 2008-SIR Annual meeting
Delay Emb-LT
EASL CR OR Specimen Nec compl.
>70% < 50% TAE 8 Pts/11 HCC 10 Mo 0% 62% 3(27%) 6 2 DC Beads 8 Pts/9 HCC 8 Mo 71% 85% 7(78%) 2 -