4 YEARS SURVIVAL OF 100 HCC PATIENTS TREATED WITH DC BEAD: A RETROSPECTIVE

ANALYSIS

Marta BurrelVascular Interventional Unit

Barcelona Clinic Liver Cancer Group Hospital Clínic. Barcelona, Spain.

Very early stage (0) Single< 2cm.

Carcinoma in situ

HCC

Portal pressure/ bilirubin

Okuda 3, PST >2, Child-Pugh C

Terminal stage (D)

Okuda 1-2, PST 0-2, Child-Pugh A-B

Stage A-C Stage D

Normal

Single 3 nodules <3cm

Associated diseasesIncreased

No Yes

Early stage ( A)Single or 3 nodules < 3cm, PS 0

Intermediate stage ( B)Multinodular, PS 0

Advanced stage (C)Portal invasion, N1,M1, PS 1-2

Stage 0

PST 0, Child-Pugh A

BCLC Classification and Treatment Schedule

Resection PEI/RF SorafenibTACE

Symptomatic treatment

Liver Transplantation (CLT / LDLT)

Curative Treatments: 50% - 75% at 5 years RCT: 40% - 50% at 3 yr vs 10% at 3yr

Forner et al. Semin Liver Dis. 2010 Feb;30(1):61-744

Lo et al. Hepatology 200235(5):1164-71 Llovet et al. Lancet 200218;359(9319):1734-9

Survival probability

TACE Control

1 year 82% 63% 2 years 63% 27%

35% objective response > 6 monthsIndependent prognostic factor

Survival probability

TACE Control

1 year 57% 32% 2 years 31% 11%

Lipiodol TACE improves survival in a selected group of HCC Lipiodol TACE improves survival in a selected group of HCC patientspatients

Favors treatment Favors control

Lin, Gastroenterology 1988 63

GETCH, NEJM 1995 159

Llovet, Lancet 2002 503

Pelletier, J Hepatol 1998 312

Bruix , Hepatology 1998 239

OVERALL 503

1010.10.01 1000.5 2

2p=0.017

Heterogeneity: Q:7.73 P=0.14

Random effects model (DerSimonian & Laird) OR (95% CI)

Author,Journal, year Cumulative (pts)

Lo, Hepatology 2002 391

2p=0.086

Median survival : ~ 20 months

Systematic Review of RCT for Unresectable HCCSystematic Review of RCT for Unresectable HCC

Llovet and Bruix. Hepatology 2002

Varela 2007 J Hepatology

Poon 2007 Clin Gastroenterol Hepatology

Malagari 2008 CVIR

# patients 27 35 62

Tumor size (mm)

46 (8-150) 76 (25-220) 56 (30-90)

Tumor response RC 29% RP 75%RO (IT) 66,6%

RC 14,3% RO 42,9%

RC 12,2%RO 80,7%

Survival 12 m 24 m 92,5% 88,9%

12 m 24 m 30 m 97% 91% 88%

Cohort studies with TACE-DC BeadsCohort studies with TACE-DC Beads

. Improved Objective Response

. Better tolerance

Bland

Embolization

(n=41) Compensate cirrhosis Child-Pugh A –B

ECOG o-1Number of nodules

No difference in both groups

Ran

do

miz

atio

n

N=

87

TACE with DCB

(n=43)

Malagari et al.Cardiovasc Intervent Radiol. 2010 Jun;33(3):541-51. Epub 2009 Nov 24.

TACE-DEB better than Bland Embolization • Local response. Overall Response (p=0.04)• Fewer recurrence. At 9 months (p=0.002)• Longer TTP (p=0.008)

Chemoembolization vs Bland EmbolizationChemoembolization vs Bland Embolization

Doxorubicin-Related Side Effects:Doxorubicin-Related Side Effects:

Precision V

End Point: Negative

Lammer et al. Cardiovasc Intervent Radiol (2010), 33(1):41-52

TACE - DC Beads: Randomised StudiesTACE - DC Beads: Randomised Studies

SURVIVAL DATA AFTER TACE IN PATIENTS SURVIVAL DATA AFTER TACE IN PATIENTS

WITH HEPATOCELLULAR CARCINOMA (HCC) IN 2010: WITH HEPATOCELLULAR CARCINOMA (HCC) IN 2010:

IMPACT ON CLINICAL PRACTICE AND RESEARCHIMPACT ON CLINICAL PRACTICE AND RESEARCH

OBJECTIVES

- Evaluate the survival of HCC patients treated with TACE-

DEB following a strict selection (preserved liver function,

absence of cancer related symptoms, extrahepatic spread or

vascular invasion)

- Evaluate causes of untreatable progression (UTP)

PATIENTS AND METHOD

HCC patients treated by TACE-DEB between February 2004

and March 2010

Retrospective review of:

- baseline characteristics- development of treatment related adverse events - overall survival

RESULTS

- 97 patients evaluated

- Median follow up 24.4 months (2.6-79.6)

- At the time of evaluation

31 patients had died

2 received transplantation

22 had received Sorafenib because of progression not

amenable for TACE

Results: Characteristics of patients

Characteristic All (n=97)BCLC-A (n=46)

BCLC-B (n=51)

Age (years) 68,2 [34-81]68,2 [42-

80]67 [34-81]

Gender (male / female) 85/12 39/7 46/5

Etiology (VHC/Alcohol/others)

58/23/4/12 27/11/6/ 2 31/13/3/4

Child-Pugh (A/B/C) 93/4 45/1 48/3

BCLC stage (A/B) 46/51 46/0 0/51

Bilirrubin (mg/dl) 1 [0,4-2,8] 1 [0,4-2,8]0,85 [0,4-

2,4]

Albumin (g/dL) 42 [29-64] 40,5 [31-

47]42 [29-64]

AFP (ng/ ml) 15,5

[1-78847]

11,5

[1-2422]

18,5

[1-78847]

Median whole cohort survival : 47.7 months (95%CI: 36.6-58.8)

Results: Survival

Survival (months)80,0060,0040,0020,000,00

1,0

0,8

0,6

0,4

0,2

0,0

Censurado

Función de supervivencia

OS 54.2 months for stage A OS 40.2 months for stage B

Survival after censoring follow-up at the time of transplant or Sorafenib 40.2 months for BCLC A 31.9 months for BCLC B31.9 months for BCLC B

Results: Survival

Early (<1 month)• Abscess• Ischemic cholecystitis • Subcapsular hematoma• Severe pain • Pancreatitis • Hepatic artery dissection

111111

Late ( >1 month)• Hepatic artery dissection• Biliary dilatation• Abscess

112

Related death 1

n=10

Results: Complications

TACETACE

No objective responseNo objective response Objective responseObjective response

Treatable(i.e. additional small HCC)

Treatable(i.e. additional small HCC) Untreatable

(i.e. vascular invasion, M1)or

Liver failure/contraindication

Untreatable(i.e. vascular invasion, M1)

orLiver failure/contraindicationTACETACE

HCC progression controlledHCC progression controlled

2nd-line option2nd-line option

ProgressionProgression

Retreatment strategyRetreatment strategy

Prof Bruix.Personal communication

Evolutionary events after TACEThe untreatable progression concept

Evolutionary events after TACEThe untreatable progression concept

Causes of untreatable progression leading to Sorafenib administration

• Significant progression after TACE• Biliary dilatation related to tumor• Extrahepatic spread• Technically not feasible• Intolerance to previous TACE-DEB

10

3

5

3

1

n= 22

J Lammer et al. Cardiovasc Intervent Radiol. 2010 Feb;33(1):41-52.

Precision V: Potential patients with UTP

1. Current survival of non-ressectable HCC patients within stages A and B is 47,7 months

2. Current survival of BCLC B patients is 40,2 months

3. These new data update the previous survival results obtained from Lipiodol-TACE, which impacts in clinical practice and research purposes

CONCLUSIONS