High-Intensity Focused Ultrasound for Hepatocellular Carcinoma Joint Hospital Surgical Grand Round Queen Mary Hospital 19/10/2013

How HIFU works Indications / Contraindications Complications Current 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 WORKS Indications / Contraindications Complications Current 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 applications 1990s: Transrectal HIFU for prostate cancer 2000s: MRI guided HIFU for uterine fibroid Under investigation: Pancreatic tumour, bone tumours etc.

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 ablationAfter ablation

Advantages / disadvantages Advantages – No internal bleeding – No needle tract seeding – Less liver derangement Disadvantages – Needs general anaesthesia – Lengthened procedure

INDICATIONS / CONTRAINDICATIONS Complications Current results Background How 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

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

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-ablationPost-ablation

COMPLICATIONS Current results Background How HIFU works Indications / Contraindications

Complications (10-20%) Skin burn Bruising Pneumothorax Incomplete ablation (10% for small tumours)

CURRENT RESULTS Background How HIFU works Indications / Contraindications Complications

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 HCC HIFU 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 cirrhosis Cheung TT et al. HPB 2013

HIFU vs. RFA HIFU (n=47)RFA (n=59)p Child-Pugh class0.001 A31 (66%)54 (91%) B16 (34%)5 (9%) Tumour size (cm)1.5 ( )1.9 ( )0.006 Complete ablation41 (87.2%)56 (94.9%)0.290 Complication rates21%9%0.060 Skin burn (n=2)Pleural effusion (n=2) Pneumothorax (n=2)Liver abscess (n=1) Chest wall oedema (n=1) Major complications6.4%6.8%>0.05 Hospital stay (day) 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 HCC Special 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 A24 (100%)24 (92%) B0 (0%)2 (8%) Tumour size (cm) >0.05 Course of treatment Median reduction in tumour size at 6 month 52.9%10.0%<0.01 Median survival (month) Wu F et al. Radiology 2005

Survival TACE only TACE + 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 TRANSPLANT Special 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 class0.267 A3 (30%)17 (58.6%) B6 (60%)12 (41.4%) C1 (10%)0 (0%) Tumour size (cm)2.6 ( )2.0( )0.960 Number of tumour1 (1-2)1 (1-3)0.172 Complete response9 (90%)1 (3%)0.00 Partial response1 (10%)14 (48%)0.00 Progressive disease014 (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