1. High Intensity Focused Ultrasound (HIFU) for Liver Tumour Dr Dai Wing Chiu Queen Mary Hospital

2. Background Treatment options for hepatocellular carcinoma  Resection  Liver transplantation  Local ablative therapy  Transarterial chemoembolization (TACE)

3. 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)

4. High Intensity Focused Ultrasound The first investigation of HIFU for non- invasive ablation were reported in the early 1940s Animal studies

5. High Intensity Focused Ultrasound Ultrasound High intensity  1000W/cm 2 to 25000W/cm 2 Focus

6. Mechanism Heating effect Cavitation Ultrasound

7. Target organ (e.g. liver) Tumor ‘Lesion’ of coagulation necrosis at focus Skin Transducer Undamaged tissue surrounding focus

8. 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.

9. HIFU AdvantagesDisadvantages No scarLong treatment time No risk of tumour seedingUSG is obstructed by bone and air-filled viscera Precise ablationNo histological diagnosis No cooling effect of perfusion (heat sink effect)

10. 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 1Group 2 Median survival (months)4.011.3P=0.004 Survival 6 months13.2%80.4%P=0.003 1 year0%42.9% Median reduction in tumour size 1 month4.8%28.6% 6 month10%52.9% 1 year0%50%P<0.01

11. 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

12. 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)

13. Demographic and Clinical Data Period 1 (n=21) Period 2 (n=20) P-value Age, years65 (48 – 84)68 (55 – 77)0.271 Sex ratio, M:F17:417:31.000 Hepatitis B surface antigen positive14 (66.7%)17 (85%)0.277 Hepatitis C virus antibody positive4 (19%)3 (15%)1.000 Child-Pugh classification0.643 Class A17 (81%)19 (95%) Class B4 (19%)3 (15%) Previous hepatic resection8 (34.7%)5 (38.4%)1.000 Previous TACE8 (38.1%)7 (35%)0.837 Serum alpha fetoprotein, ng/ml10 (2-3951)10 (3-8840)0.766

14. Tumor and Treatment Data Period 1 (n=21) Period 2 (n=20) P-value Size of largest tumor, cm2.7 (0.9 – 5)2.1 (1 – 5)0.733 No. of tumors treated (solitary / 2 lesions) 19 / 216 / 40.410 Artificial right pleural effusion during HIFU 13 (61.9%)13 (65%)1.000 Total treatment duration, min43 (10 – 125)24 (3 – 122)0.039 Average acoustic power, watt351 (230 – 467)429 (155 – 473)0.074

15. Results Period 1 (n=21) Period 2 (n=20) P-value Treatment-related mortality1 (4.8%)-1.000 Treatment-related complications3 (14.2%)2 (10%)1.000 Second degree skin burn2- Chest wall bruising12 Hospital stay, days3 (2 – 16)4 (2 – 11)0.792 Complete tumor ablation a 13 (65%)19 (95%)0.044 Complete tumor ablation b 15 (68%)23 (96%)0.009 a: Complete ablation rate in terms of number of patients b: Complete ablation rate in terms of number of tumor nodules

16. Overall Survival Months 20100 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

17. 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

18. Discussion Its application as a non-invasive surgical tool is still in its infancy Limitations and challenges Indications Limited evidence