Guideline Development Discussion

Moderated by: Professor Hee Chul Park

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

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

2012 EASL-EORTC (Updated BCLC Staging)

Llovet et al. J Hepatology 2012;56:908

2012 NCCN

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

KLCSG & NCC, Korea. Korean J Hepatol 2009;15(3):391-423

2009 Korean Liver Cancer Study Group

Chinese Society of Liver Disease

Suggestions by RO Experts

Other suggestions (RT role for HCC)

Lee IJ, Seong J. Oncology 2011;81(S1):123-33Gut and Liver 2012;6(2):139-48

Other suggestions (RT role for HCC)

Lee IJ, Seong J. Gut and Liver 2012;6(2):139-48

Unsuitable for Op, TPL, RFA

TACE 1-5 sessions

NCT0182582460 Gy/3 Fx

NCT0185066745~60 Gy/3 Fx

NCT01850368

40 Gy/4 Fx

No Clinical Trials

Debulking SBRT

Sum ≤ 5 cm & 3 cm from GI tract

Sum ≤10 cm

Yes

No Yes

No

Normal Liver Dose-ConstraintsrV15<700 ml (CP A5), rV17<700 ml (CP A6-B7) No

Incomplete TACE

Complete TACE

Observation

Dawson L. Semin Radiat Oncol 2011;21:241-246

Other suggestions (RT role for HCC)

Discussions

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

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

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

RT role for HCC

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

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 19862) Hawkins et al. Cancer 20063) Seong et al. Yonsei Med J 20094) Hoffe et al. Cancer Control 20105) Krishnan et al. Ann Surg Oncol

2008

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.”

nodular massive with intrahepatic metastasis

diffuse vascular invasion

Park et al. Oncology 2011

Sub-classification of Locally advanced HCC