1. Radiotherapeutic Option in Management of Hepatocellular Carcinoma
Dr. CK Tang, Tuen Mun Hospital

2. Overview External beam radiotherapy Transarterial radioembolisation
Aim : Overview of clinical use of external beam radiotherapy in HCC patients

3. Background Hepatocellular carcinoma HCC
5th most common cancer in the world
3rd ranked cause of global cancer mortality
Worldwide Incidence of HCC

4. Background Multidisciplinary management of HCC Aggressive treatment
Increasing interest in radiotherapy as an option of management for HCC

5. Background Traditionally, radiotherapy is regarded as of limited use
Radiation-induced liver disease RILD
Low dose radiation
Relatively diffuse field
“Radio-resistant”

6. Background New technologies :
Advanced imaging to improve tumour definition
3D conformal treatment planning
Computer-assisted organ tracking
Intensity modulated RT
Improved knowledge of partial volume tolerance of liver
Advanced imaging to improve tumour definition
3D confromal treatment planning
Computer-assisted organ tracking
Image modulated RT
Improved knowledge of partial volume tolerance of liver

7. Background
Greater conformality of the radiation dose cloud around liver tumors
Less radiation delivered to surrounding “normal liver”
Higher radiation dosage could be delivered to tumour up to 70 Gy
Stereotactic body radiotherapy SBRT

8. Clinical Questions Is it useful ?
Which patient group are we going to offer to ?
What are the outcomes ?

9. Is it useful ?

10. Evidence
Radiotherapy for hepatocellular carcinoma: Systematic review of radiobiology and modeling projections indicate reconsideration of its use
Wigg et al 2010
Level I evidence that HCC is radiosensitive

11. Evidence
Early results came from experience in palliative care

12. Evidence
Bujold et al.
Phase II prospective series including 102 patients
High risk
Extrahepatic disease
Large size HCC up to 7cm
Main portal vein thrombosis

13. Evidence Bujold et al. Overall local control at 1 year was 87%.
Median overall survival was 17.0 months
1-year survival rate compared favorably with best supportive care and with sorafenib
Conclusion : SBRT has substantial local control activity against HCC

14. Evidence
Feasibility and efficacy of high-dose three-dimensional-conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma non-eligible for curative therapies – mature results of the French phase II RTF-a trial
Mornex et al 2006
Stereotactic body radiotherapy for primary hepatocellular carcinoma
Andolino et al. 2011
85-95% response rate

15. Which patient group are we going to offer radiotherapy to?

16. We don’t know.
No RCT
No guideline
Expert opinion

20. Preserved liver function
Huge tumour
Main portal vein thrombus

21. Evidence Synergistic effect of TACE with RT Direct tumour necrosis
Veno-occlusive effect of RT to surrounding liver tissue

22. Preserved liver function
Huge tumour
Main portal vein thrombus

23. What are the outcomes ? Local control activity against HCC
And apart from that…

24. Case presentation 1 55 year-old gentleman Attended TMH
Non-Hep B, non-Hep C HCC
AFP 1085
Child’s A
CT : 10.4cm HCC at right lobe
BCLC stage C

25. Case presentation 1
TACE to RHA, then stereotactic radiotherapy 4 Gy x 9
Follow-up CT : Interval decrease in size of HCC to 6.2cm, with hypertrophy of left lateral section
CT volumetry : 57%

26. Case presentation 1
Before
After

27. Case presentation 1
Right tri-sectionectomy 6 months after initial diagnosis of HCC

28. Case presentation 1

29. Case presentation 2 Child’s A Presented to us for RUQ pain
CT : Huge HCC occupying the right lobe, contained rupture

30. Case presentation 2 TACE, then stereotactic radiotherapy 4 Gy x 8
Follow-up CT : Interval decrease in size of HCC from 13.4cm to 9cm
Hypertrophy of left lateral section

31. Case presentation 2
Right hepatectomy 6 months after initial diagnosis of HCC
Before
After

32. Combination of Radiotherapy with other modalities
Choi SB et al. 2009
Case series
16 patients with HCC greater than 5 cm in size
TACE and radiation therapy, then resection
Median survival 13.3 months
5 patients had survived more than 2 yr and 2 patients who had survived more than 5 yr

33. Combination of Radiotherapy with other modalities
Hung KC et al. 2011

34. Combination of Radiotherapy with other modalities
Hung KC et al. 2011

35. Summary
Is it useful ?
Level I evidence to support radio-sensitivity of HCC
Prospective studies to support local control activity in HCC
Whom to select ?
No RCT, no guideline
Expert opinion
Huge tumour, MPV thrombus, Preserved liver function

36. Summary What are the clinical outcomes ?
Prospective studies support the clinical use of radiotherapy for local control
A few case reports and small case series to support combination of radiotherapy and TACE with surgical resection

37. Summary
But still lacking RCTs to provide comparison with other treatment modalities, in terms of survival benefit
Relatively new approach with scanty clinical data meanwhile
Controversy

38. Future perspective ? Overall survival ? Disease-free survival
Evidence limited to prospective studies, case reports and case studies
Evidence concentrated in Asia
No RCT
Data are emerging
China
Japan
Korea

39. As a Surgeon… Overview only
Share our experience of managing patients with radiotherapy
As a Surgeon…
Multidisciplinary approach in management of HCC
Operation is only a part of it
Explore combination of radiotherapy with resection / ablative surgery / liver transplantation
Ongoing research should be promoted

41. Adverse reactions

42. Limitations
Evidence limited to prospective studies, case reports and case studies
Evidence concentrated at Asia
No RCT conducted
Limited to a selected group of patient
No generalised selection criteria
No homogeneous treatment protoccol

43. Radiation-induced liver disease
Radiation hepatitis
Fatigue, RUQ pain, ascites, jaundice, elevated liver enzymes
Develops usually 1-2 months after RT (range 2 weeks - 8 months)
Treatment: supportive; most patients recover, but can lead to liver failure and death

44. Radiation-induced liver disease
Dawson report in 2002
The mean liver dose is directly proportional to risk of RILD
5% risk of RILD for whole liver RT is at 32 Gy
Small liver volumes (<25%) can tolerate doses >100 Gy
Difference between normal liver tolerance and HCC liver tolerance