High-Intensity Focused Ultrasound for Hepatocellular Carcinoma

High-Intensity Focused Ultrasound for Hepatocellular Carcinoma

Joint Hospital Surgical Grand RoundQueen Mary Hospital

19/10/2013

How HIFU worksIndications / ContraindicationsComplicationsCurrent results

BACKGROUND

Hepatocellular carcinoma

• Most common primary liver cancer

• Only 15% resectable disease on presentation– Inadequate liver function– Multifocality

• Local ablative therapies for unresectable disease

Local ablative therapy

• Radiofrequency ablation• Ethanol injection• Microwave ablation

• High-intensity focused ultrasound

HOW HIFU WORKSIndications / ContraindicationsComplicationsCurrent results

Background

High-Intensity Focused Ultrasound

• Focused ultrasound energy (0.8MHz) from distant transducer

• Hyperthermia• Coagulative necrosis

• Intact tissues in between

• Animal studies in 1940s• Intended for treatment

of Parkinson disease

Current clinical applications1990s: Transrectal HIFU for prostate cancer

2000s:MRI guided HIFU for uterine fibroid

Under investigation: Pancreatic tumour, bone tumours etc.

Ultrasound guided HIFU system

Ultrasound guided HIFU system

Water tank

Therapeutic ultrasound transducer

Diagnostic ultrasound probe

Procedure

• General anaesthesia– Immobilization– Interval cessation of

ventilation

• Prone / right lateral position

Procedure

• Planning with diagnostic ultrasound

• Slice-by-slice ablation from deep to superficial region

Grayscale change

Before ablation After ablation

Advantages / disadvantages

• Advantages– No internal bleeding– No needle tract seeding– Less liver derangement

• Disadvantages– Needs general anaesthesia– Lengthened procedure

INDICATIONS / CONTRAINDICATIONSComplicationsCurrent results

BackgroundHow HIFU works

Indications

• Small tumour– Less than 3cm: ablation rate >85%

• Centrally located / liver dome tumour• Adjacent to major bile duct / veins

• Child’s C liver function• Gross ascites

Cheung TT et al. HPB 2013

Liver dome tumour

Liver dome tumour

Tumour adjacent to major vein

Tumour adjacent to major vein

Indications

• Small tumour– Less than 3cm: ablation rate >85%

• Centrally located / liver dome tumour• Adjacent to major bile duct / veins

• Child’s C liver function• Gross ascites

Gross ascites

Contraindications

• Not fit for general anaesthesia• Cannot assume treatment position

• Very poor liver function

• Lesion not visualized by USG• Overlying hollow viscus• Deep tumour• Tumour close to overlying rib

Deep tumour

Tumour close to rib

Pre-ablation Post-ablation

COMPLICATIONSCurrent results

BackgroundHow HIFU worksIndications / Contraindications

Complications (10-20%)Skin burn Bruising

• Pneumothorax• Incomplete ablation (10% for small tumours)

CURRENT RESULTS

BackgroundHow HIFU worksIndications / ContraindicationsComplications

• Unresectable HCC (n=49)– Child’s A (n=41) and B (n=8) cirrhosis– Median size 2.2cm (0.9-8cm)

Ng KK et al. Annals of Surgery 2011

Unresectable HCC

• Ablation rate 79.5% (n=39)

• Risk factor: median tumour size (2.3cm vs. 3.8cm; p=0.03)

Ng KK et al. Annals of Surgery 2011

SMALL HCCHIFU v.s. RFA

• Small (<3cm) unresectable HCC (n=106)– Percutaneous RFA if feasible (n=59)– HIFU (n=47) if• Technically difficult percutaneous RFA

– Liver dome tumour– Ascites

• Child’s B cirrhosisCheung TT et al. HPB 2013

HIFU vs. RFAHIFU (n=47) RFA (n=59) p

Child-Pugh class 0.001

A 31 (66%) 54 (91%)

B 16 (34%) 5 (9%)

Tumour size (cm) 1.5 (0.8-2.7) 1.9 (1.0-2.8) 0.006

Complete ablation 41 (87.2%) 56 (94.9%) 0.290

Complication rates 21% 9% 0.060

Skin burn (n=2) Pleural effusion (n=2)

Pneumothorax (n=2) Liver abscess (n=1)

Chest wall oedema (n=1)

Major complications 6.4% 6.8% >0.05

Hospital stay (day) 4 6 0.028

Cheung TT et al. HPB 2013

Survival

34%

26%

81%80%

Cheung TT et al. HPB 2013

TUMOURS CLOSE TO PEDICLES

• Liver tumours (n=30) and pancreatic tumours (n=6)• Tumour <1cm from – IVC / hepatic /portal veins (n=27)– Bile ducts (n=4)

• 1 portal vein thrombosis (Pancreatic cancer)• No bile duct injury

Franco O et al. AJR 2013; 195

• HCC (n=39) with close proximity to major veins

• No venous thrombosis / bile duct injury

Zhang L et al. Eur Radiol 2008

LOCALLY ADVANCED HCCSpecial condition

• Locally advanced (4-14cm, mean 10.5cm) HCC (n=50)– Randomized controlled trial– TACE + HIFU (n=24)– TACE only (n=26)

Wu F et al. Radiology 2005

TACE + HIFU vs. TACE

TACE + HIFU(n=24) TACE (n=26) p

Child-Pugh class >0.05

A 24 (100%) 24 (92%)

B 0 (0%) 2 (8%)

Tumour size (cm) 10.03 11.26 >0.05

Course of treatment 1.2 1.5

Median reduction in tumour size at 6 month

52.9% 10.0% <0.01

Median survival (month) 11.3 4.0 0.004

Wu F et al. Radiology 2005

Survival

TACE onlyTACE + HIFU

Wu F et al. Radiology 2005

Locally advanced HCC

• Combined HIFU / TACE is a promising approach

• On-going trial in QMH

Wu F et al. Radiology 2005

BRIDGING TO TRANSPLANTSpecial condition

• Retrospective study

• Transplant candidates for HCC (n=49)– Bridging HIFU (n=5)– Bridging TACE (n=29)– No bridging therapy (n=15)

• Non-transplant candidates with HIFU (n=5)

Cheung TT et al. WJG 2013

Bridging to transplant

HIFU(n=10) TACE (n=29) p

Child-Pugh class 0.267

A 3 (30%) 17 (58.6%)

B 6 (60%) 12 (41.4%)

C 1 (10%) 0 (0%)

Tumour size (cm) 2.6 (1.2-4.0) 2.0(0.8-4.3) 0.960

Number of tumour 1 (1-2) 1 (1-3) 0.172

Complete response 9 (90%) 1 (3%) 0.00

Partial response 1 (10%) 14 (48%) 0.00

Progressive disease 0 14 (48%) 0.00

Cheung TT et al. WJG 2013

Bridging to transplant

• 3 patients in HIFU group received liver transplant

• Pathology– Complete necrosis (n=2)– 90% necrosis (n=1)

Cheung TT et al. WJG 2013

Liver transplant candidate

• Effective bridging therapy to liver transplant

Cheung TT et al. WJG 2013

Summary

• Current applications– Ablative therapy for small unresectable HCC• Child’s C liver function • Tumour close to major pedicle

– Combined with TACE for large HCC– Bridging therapy to liver transplantation

• Under investigation• More clinical studies warranted