Moderated by: Professor Hee Chul Park

1. Guideline Development Discussion
Moderated by: Professor Hee Chul Park

2. 1. Radical therapies (40%)
- resection, liver transplantation (CLT/LDLT),
local ablation (RFA, PEIT)
2. Palliative therapies (40-50%)
- TACE, Radiotherapy, Targeted therapy, HAIC,
- Combined treatment (RT+TACE, CCRT, etc)
- others (radioembolization, hormone,
immunotherapy, anti-proliferative agents)
3. Symptomatic treatment (10-20%)
- Best supportive care
Treatment options for HCC management

3. Guidelines Mention of RT as a treatment option
APASL (2009) No
KLCSG (2009) Consolidate TACE, Portal invasion,
Symptom palliation
JSH (2005/2007/2010) 2005/palliative RT aimed at pain relief
AASLD (2005/2010) 2005/one of non-curative treatment
2010/alleviate pain in bone metastasis
NCCN (2012) Unresectable (unable to transplant),
Inoperable local disease
EASL-EORTC (2012) No evidence/under investigation
Chinese Society of Liver Disease Vascular invasion/Extrahepatic spread
RT in the HCC management guidelines

4. 2012 EASL-EORTC (Updated BCLC Staging)
Llovet et al. J Hepatology 2012;56:908

5. 2012 NCCN
NCCN Guidelines. Hepatobiliary Cancer. V2.2012. Available at: www.nccn.org

6. KLCSG & NCC, Korea. Korean J Hepatol 2009;15(3):391-423
2009 Korean Liver Cancer Study Group

7. Chinese Society of Liver Disease

8. Suggestions by RO Experts

9. Other suggestions (RT role for HCC)
Lee IJ, Seong J.
Oncology 2011;81(S1):123-33
Gut and Liver 2012;6(2):139-48

10. Other suggestions (RT role for HCC)
Lee IJ, Seong J. Gut and Liver 2012;6(2):139-48

11. Unsuitable for Op, TPL, RFA
TACE 1-5 sessions
NCT01825824
60 Gy/3 Fx
NCT01850667
45~60 Gy/3 Fx
NCT01850368
40 Gy/4 Fx
No Clinical
Trials
Debulking
SBRT
Sum ≤ 5 cm & 3 cm from GI
tract
Sum ≤10 cm
Ye
s
No Ye
s
No
Normal Liver Dose-Constraints
rV15<700 ml (CP A5), rV17<700 ml (CP A6-B7) No
Incomplete TACE
Complete TACE Observation

12. Dawson L. Semin Radiat Oncol 2011;21:241-246
Other suggestions (RT role for HCC)

13. Discussions

14. RT in BCLC Staging System
TACE+RT/CCRT
-Consolidate TACE
-Salvage TACE
refractoriness(SABR)
-Portal invasion
Palliative RT
-Symptom control
-Prevention of cancer
related morbidity
-Oligometastasis
SABR/HypoFx RT/TACE+RT
-Inoperable
-Inaccessible
-To bridge before LT
-Salvage recurrence
Support from evidence-making clinical trial efforts

15. 1. Clinical Indication / or situation
- As ablative, curative
- As palliative, for local control
- As palliative, for symptom alleviation
2. RT only / As Combined Treatment
- Radiotherapy Only
- Combined treatment (TACE, HAIC, sorafenib, etc)
3. Technical Issues
- Fractionation (SABR, HypoFx, Conventional Fx)
- Conformal RT / IMRT /
RT Application Guideline for HCC management

17. 17
Standardizing protocol?
 What criteria do you include in selecting the patients?
 What is the impact of target delineation strategies?
 What dose and fractionation scheme do you typically use when
performing a CK or TT treatment?
 How do you choose the treatment margins for CK or TT?
 In what ways do you apply image guidance and motion management
into the treatment strategies?
 What follow-up methods do you use in your practice?
 How do you make informed treatment decisions based on the clinical
evidence level?
 What should be the ideal timeline of the guideline consensus?
 How can we connect the guidelines to medical associations in
different countries?
SBRT (CyberKnife) and IG-IMRT (TomoTherapy)
Consensus to questions -
#XXXXXXX — Company Confidential

18. RT role for HCC

19. Ablative RT for small HCC (< 3cm)
1. SABR (Stereotaxic Ablative Body Radiotherapy
- high RT dose with precision and accuracy
- generally 1-4 fractions (hypofractionated RT)
2. Clinical indication
- in general, within Milan criteria
- unresectable/Inoperable, not transplantable
- Ineligible to RF ablation
due to inconspicuity, expected heat sink effect,
exophytic/peripheral location with seeding risk,
central location near bile duct or bowel
bleeding tendency
- adequate liver function reserve
- sufficient distance from radiosensitive OAR
- well delineated on CT or MRI for RT planning

20. Combined RT with TACE for HCC(>3 cm)
1. Two different application
- salvage TACE refractoriness after repeated TACE
- consolidate residual viability of HCC after TACE
2. Rationale combining RT to TACE
- tumor remains viable in and around capsule1-2)
- recurrence via the parasitic blood supply3)
- recurrence from recanalization of embolized artery4)
- presence of vascular shunting interferes effective TACE5)
- chemoagents(@TACE) stays enough long to sensitize
radiation effect3)
1) Hsu et al. Cancer 1986
2) Hawkins et al. Cancer 2006
3) Seong et al. Yonsei Med J 2009
4) Hoffe et al. Cancer Control 2010
5) Krishnan et al. Ann Surg Oncol

21. RT role for HCC with vascular invasion
1. Vascular invasion (common Cx of HCC) can cause
- accompanying extensive vascular shunt  ineffective TACE
- portal hypertension deteriorates liver function
 arterial embolization can cause hepatic failure
- cause lung metastasis, heart failure, and pulmonary TE
2. RT response of vascular invasion (PVTT, IVCTT) can
- delay intravascular tumor growth
- delay liver function deterioration by preserving vascular flow
- decrease the risk of sudden death
- facilitate the subsequent treatment of HCC
“Sufficient RT response is mandatory for the RT effect.”

22. nodular massive with intrahepatic
metastasis
diffuse vascular invasion
Park et al. Oncology 2011
Sub-classification of Locally advanced HCC