High Intensity Focused Ultrasound (HIFU) for Liver Tumour

Dr Dai Wing Chiu

Queen Mary Hospital

Background

Treatment options for hepatocellular carcinoma

Resection Liver transplantation Local ablative therapy Transarterial chemoembolization (TACE)

Local Ablation Therapy

The first description of percutaneous ethanol injection (PEI)

Liveraghi T et al. Radiology 1986

Thermal techniques were first performed in the liver using single bare tip neodymium yttrium aluminium garnet (NdYAG) laser fibres

Steger A et al. BMJ 1989

Five thermal techniques Radiofrequency ablation Laser Microwave Cryotherapy High intensity focused ultrasound (HIFU)

High Intensity Focused Ultrasound The first investigation of HIFU for non-invasiv

e ablation were reported in the early 1940s

Animal studies

High Intensity Focused Ultrasound Ultrasound

High intensity 1000W/cm2 to 25000W/cm2

Focus

Mechanism

Heating effect Cavitation

Ultrasound

Target organ (e.g. liver)

Tumor

‘Lesion’ of coagulation necrosis at focus

Skin

Transducer

Undamaged tissue surrounding focus

HIFU at Queen Mary Hospital

HIFU service for HCC started in Oct 2006 thanks to donation of the USG-guided HIFU system by Chongqing Haifu Co.

HIFU

Advantages Disadvantages

No scar Long treatment time

No risk of tumour seeding USG is obstructed by bone and air-filled viscera

Precise ablation No histological diagnosis

No cooling effect of perfusion (heat sink effect)

HIFU – Current evidence 50 consecutive patients with stage IVA HCC Group 1 (n=26) - TACE alone Group 2 (n=24) – TACE with HIFU performed 2-4 weeks afterwards Tumours size 4-14cm (mean 10.5cm) FU 3-24 months (mean 8 months)

F Wu et al. Radiology 2005

Group 1 Group 2

Median survival (months) 4.0 11.3 P=0.004

Survival

6 months 13.2% 80.4% P=0.003

1 year 0% 42.9%

Median reduction in tumour size

1 month 4.8% 28.6%

6 month 10% 52.9%

1 year 0% 50% P<0.01

HIFU – Current evidence

55 patients with HCC Prospective, non-randomized clinical trial Tumour size 4-14cm in diameter (mean 8.14cm) Serum AFP returned to normal level in 34% of patient Overall survival rates at 6, 12 and 18 months were 86.1%, 61.5%

and 35.3%, respectively Survival rates were significantly higher in patients in stage II than

those in stage IIIA (p=0.0132) and in stage IIIC (p=0.0265).

Wu F et al. Ann Surg Oncol 2004

HIFU at Queen Mary Hospital

From October 2006 to April 2008, totally 41 patients with unresectable HCC received HIFU treatment

Initial 21 patients received HIFU with transarterial embolization (TAE) (Period 1), and subsequent 20 patients received HIFU without TAE (Period 2)

Demographic and Clinical Data

Period 1

(n=21)

Period 2

(n=20)

P-value

Age, years 65 (48 – 84) 68 (55 – 77) 0.271

Sex ratio, M:F 17:4 17:3 1.000

Hepatitis B surface antigen positive 14 (66.7%) 17 (85%) 0.277

Hepatitis C virus antibody positive 4 (19%) 3 (15%) 1.000

Child-Pugh classification 0.643

Class A 17 (81%) 19 (95%)

Class B 4 (19%) 3 (15%)

Previous hepatic resection 8 (34.7%) 5 (38.4%) 1.000

Previous TACE 8 (38.1%) 7 (35%) 0.837

Serum alpha fetoprotein, ng/ml 10 (2-3951) 10 (3-8840) 0.766

Tumor and Treatment Data

Period 1

(n=21)

Period 2

(n=20)

P-value

Size of largest tumor, cm 2.7 (0.9 – 5) 2.1 (1 – 5) 0.733

No. of tumors treated

(solitary / 2 lesions)

19 / 2 16 / 4 0.410

Artificial right pleural effusion during HIFU

13 (61.9%) 13 (65%) 1.000

Total treatment duration, min 43 (10 – 125) 24 (3 – 122) 0.039

Average acoustic power, watt 351 (230 – 467) 429 (155 – 473) 0.074

Results

Period 1

(n=21)

Period 2

(n=20)P-value

Treatment-related mortality 1 (4.8%) - 1.000

Treatment-related complications 3 (14.2%) 2 (10%) 1.000

Second degree skin burn 2 -

Chest wall bruising 1 2

Hospital stay, days 3 (2 – 16) 4 (2 – 11) 0.792

Complete tumor ablationa 13 (65%) 19 (95%) 0.044

Complete tumor ablationb 15 (68%) 23 (96%) 0.009

a: Complete ablation rate in terms of number of patientsb: Complete ablation rate in terms of number of tumor nodules

Overall SurvivalO

ve

rall

Su

rviv

al

Months20100

100

90

80

70

60

50

40

30

20

10

0

P = 0.074

Period 2

Period 1

Short-term survival outcome between the two groups

(period 1 vs. period 2) were similar

(86.5% vs. 79% at 1 year, P = 0.074)

Period 2

Period 1

Indications for HIFU at QMH

Unresectable primary or recurrent HCC

(inadequate liver function, multifocal HCC, proximity to major vessels) Curative intent Tumor size < 10 cm < 3 tumor nodules No venous invasion No extrahepatic metastasis General condition fit for general anesthesia

Discussion

Its application as a non-invasive surgical tool is still in its infancy

Limitations and challenges Indications Limited evidence