Interventional Treatment for Interventional Treatment for Hepatocellular CarcinomaHepatocellular Carcinoma

Sheng-Long Ye, MD, PhD

Liver Cancer Institute

Zhongshan Hospital

Fudan University

Shanghai, China

China—High Incidence of Liver Cancer

New Cases of Liver Cancer (2008)

748

x103

402

48.2%

6

Deaths of Liver Cancer (2008)

694

x103

372

48.4%

6

3

The Second Cancer Killer in ChinaThe Second Cancer Killer in China

0

5

10

15

20

25

30

35

Nati onwi de Urban Rural

1973-19751990-19922004-20052006

PLC Mortality (per 10PLC Mortality (per 1055 people) people)

Problem in HCCProblem in HCC

Severe Severe cirrhosiscirrhosis Intrahepatic Intrahepatic spread spread and and

distant distant metastasismetastasisLowLow resectabilityresectabilityHigh postoperative High postoperative

recurrencerecurrence

HCC

PS 0~2 PS 3~4

Child-Pugh A/B Child-Pugh C

ECOG

Liver Function

Metastasis No Yes

Vascular Invasion

Number

Tumor size

No Yes

≤3cm ＞3cm

≥42~3

•Supportive care

•Supportive care

•Transplant (UCSF)

•TACE

•Radiotherapy

•Molecular targeted

•Systemic chemotherapy

•TACE

•Resection

•+ablation

•Resection

•TACE

+Ablation

•Transplant (UCSF)

•Resection

•Ablation (≤3cm)

•Transplant

Optimal treatment

•TACE

•Resection

•Radiotherapy

•Targeted

•Systemic chemotherapy

Single

HCC Treatment Algorithm

≤5cm ＞ 5cm

Non-surgical TreatmentNon-surgical Treatment Interventional treatment –

TACE, Intratumor injection, RFA, MWCT, Laser, HIFU, Cryotherapy

Radiotherapy Chemotherapy Biotherapy Molecular targeted therapy Traditional Chinese medicine

Interventional Treatment is a main modality for HCC

1995

Murakami

Microwave

1976GoldsteinTAE

1979Nakakuma Lipiodol TACE

1986LivraghiPEI 1986

OnikCryoablation

1992MastersLaser

1993Rossi RFA

1994OhnishiPAI

TIPS, stent in IVC, biliary tract, portal vein……

Key Pathologic Features of HNS: Vascular Supply

Normal PV

Arterial supply

Portal supply

RN low-DN high-DN EHCC wd-HCC md/pd-HCC

ClassicNormal HA

Abnormal HA

Loss of visualization of portal tracts and development of new arterial vessels

Significant overlap

Llovet JM, et al. Hepatology. 2003;37:429-442.

Arterial Embolization for HCCMeta-analysis of 6 RCTs (2-Yr Survival)

Random Effects Model,OR (95% CI)

Author, Journal Yr Patients,

n

Lin, Gastroenterology 1988 63

GETCH, NEJM 1995 96

Bruix, Hepatology 1998 80

Pelletier, J Hepatol 1998 73

Lo, Hepatology 2002 79

Llovet, Lancet 2002 112

Overall 503

Median survival: ~ 20 mos

0.01 0.1 0.5 1 2 10 100

Z = -2.3P = .017

Favors Treatment

Favors Control

HCC

PS 0~2 PS 3~4

Invasion

Child-Pugh C

No Yes

ECOG

Liver Function

Metastasis

Child-Pugh A/B

No Yes

Tumor Number

·TACE·Radiotherapy·Sorafenib·Chemotherapy

·TACE·Resection·Radiotherapy·Sorafenib·Chemotherapy

One 2~3 ≥4

Tumor Size

≤3cm ＞ 3cm

Treatment ·TACE·Resection·+Ablation•Transplant

·Resection·TACE+RFA·Transplant

< 5cm ≥5m

Application of TACE for HCCApplication of TACE for HCC

Improvement of TACE H.A.-P.V. combined embolization Super selective segmental

chemoembolization TACE with temporary occlusion of H.V. Hot lipiodol embolization Segmental ethanol-lipiodol infusion Stent in P.V. with I125 intra-radiation Radioembolization (Y90 microsphere) Drug-Eluting Bead embolization

Personalization of TACEPersonalization of TACE

Super-selective embolizationSuper-selective embolization Prolongation of treatment intervalProlongation of treatment interval Tumor down-staging resectionTumor down-staging resection Adjuvant TACEAdjuvant TACE Thrombus in P.V. and I.V.C.Thrombus in P.V. and I.V.C. Combination treatmentCombination treatment Avoiding over-treatment Avoiding over-treatment !!

Local Ablation therapy

Clinical departments involving in ablation therapy

---- Surgical, Medical, Interventional, Radiology,

Radiotherapy, Ultrasonography…）

Imaging-guided targeting

cancer location, resulting in

direct coagulation, necrosis

and killing of cancer tissues

by physical and chemical

approaches with minimal

invasion

Safe, minimal-invasion,

simplified ， repeatable

Local AblationLocal Ablation PEI, RFA, MWCT, Laser thermal therapy, HIFU, PEI, RFA, MWCT, Laser thermal therapy, HIFU,

(Argon-Helium)-Cryotherapy.(Argon-Helium)-Cryotherapy. All tumors amenable to ablation (enough margin of All tumors amenable to ablation (enough margin of

normal tissues).normal tissues). Tumors in a location accessible for ablation.Tumors in a location accessible for ablation. Tumors ≤ 3cm --- optimally treated with ablation . Tumors ≤ 3cm --- optimally treated with ablation . Tumor 3-5cm --- combination of embolization and Tumor 3-5cm --- combination of embolization and

ablation. ablation. Unresectable/inoperable lesions (Unresectable/inoperable lesions ( ＞＞ 5cm) -– arterial 5cm) -– arterial

embolization approaches.embolization approaches. Caution --- ablating lesions near major vessels, Caution --- ablating lesions near major vessels,

major bile ducts and other intra-abdominal organs.major bile ducts and other intra-abdominal organs.

Ablation area should include at least 5 cm of surrounding tissues for “safe margin”

Ablation area needs to be extended for liver cancer with infiltrative type or metastatic type if the surrounding tissues and structure are available

Personalization of treatment strategy is important for liver cancers near heart, diagram, stomach, intestine, gallbladder and other organs

Blood-supply vessels of hypervascular cancer may be blocked before ablation

Principles of Ablation therapy

RFA for Small HCCRFA for Small HCC

Jiang XC

Wang ZS

RFA for Small HCCRFA for Small HCC

Wang ZS

Mao YY

RFARFA - CEUS- CEUS

Small HCC: RFASmall HCC: RFA vs Surgeryvs Surgery

RecurrenceRecurrence% 1-y 2-y 3-y% 1-y 2-y 3-y

Resection 65 10.7 18.4 24.6Resection 65 10.7 18.4 24.6

RFA 47 8.5 19.1 23.4RFA 47 8.5 19.1 23.4

SurvivalSurvival% 1-y 2-y 3-y 4-y 5-y% 1-y 2-y 3-y 4-y 5-y

Resection 90 93.9 89.1 80.0 67.4 48.6Resection 90 93.9 89.1 80.0 67.4 48.6

RFA 71 90.7 83.3 74.9 57.0 47.2 RFA 71 90.7 83.3 74.9 57.0 47.2

HCC(≤4cm): RFAHCC(≤4cm): RFA vs Surgeryvs Surgery

RecurrenceRecurrence% 1-y 2-y 3-y% 1-y 2-y 3-y

Resection 84 Resection 84 8.3 20.2 32.1 8.3 20.2 32.1

RFA 84 11.9 27.4 41.7RFA 84 11.9 27.4 41.7

SurvivalSurvival% 1-y 2-y 3-y% 1-y 2-y 3-y

Resection 84 96.0 87.6 74.8Resection 84 96.0 87.6 74.8

RFA 84 93.1 83.2 67.6 RFA 84 93.1 83.2 67.6

HCC

PS 0~2 PS 3~4

Vessel Invasion

Child-Pugh C

No Yes

ECOG

Liver Function

Metastasis

Child-Pugh A/B

No Yes

Tumor Number One 2~3 ≥4

Tumor Size

≤3cm ＞ 3cm

Treatment ·TACE·Resection·+Ablation•Transplant

·Resection·Ablation≤3cm·Transplant

·Resection·TACE+Ablation·Transplant

< 5cm ≥5m

Application of Ablation for HCC

Combination of TACE and ablation prolongs

survival of cancer patients with multiple

nodules

Wang, et al. Liver International 2010Wang, et al. Liver International 2010

05

1015

2025303540

455-y10-y

TACE PEI

Outcome of Non-Surgical PLC (1995-2009）

25.3%

37.9%

44.6%

41.0%

32.8%

44.7%

RF RF+TACE TACE+PEI RF+PEI RF+PEI+TACE

37.7%

Evidence Levels in the Treatment of HCC according to the strength of study design

and of end-points

Treatments assessed Benefit Evidence level

Surgical treatments Surgical resection Increased survival 3iiA Adjuvant therapies Controversial 1A-D Liver transplantation Increased survival 3iiA Neo-adjuvant therapies Treatment response

3Diii

Loco-regional treatments Percutaneous treatments Increased survival 3iiA Radiofrequency ablation Better local control 1iiD Chemoembolization Increased survival 1iiA Lipiodolization Treatment response 3iiDiii

Internal radiation (I131, Y90) Treatment response 3iiDiii

Systemic treatments Sorafenib Increased survival 1iA Tamoxifen No survival benefit 1iA Systemic chemotherapy No survival benefit 1iiA Immunotherapy No survival benefit 1iiA

Llovet & Bruix: J Hepatol, 2008; 48: S20-S37

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