HCC Guidelines and recommendation 2013

Typical feature (wash in/wash out)

New mass/nodule

No Yes

Alternative imaging technique

Atypical feature Typical feature

Biopsy

Increase (Ø ≥ 1 cm)

No Yes

US 3 months

Ø < 1cm

TC/RM/CEUS*

Ø ≥1cm

Increase (Ø ≥ 1 cm)

US 3 months(for 12 months)

No

US 6 months

Yes

Other diagnosis

HCC

Inconclusive

Diagnostic algorithm

US, Ultrasound; MRI, Magnetic resonance imaging; CT, computed tomography; CEUS, contrast-enhanced ultrasonography *Since magnetic resonance imaging (MRI) or computed tomography (CT) would be performed for hepatocellular carcinoma staging after detection of a nodule by ultrasonography, the most cost-effective approach is to prescribe in first line MRI or CT and to resort to contrast-enhanced ultrasonography (CEUS) in case of inconclusive diagnosis at MRI and/or CT .Position paper AISF DLD 2013 45(2013) 712-723

Diagnostic algorithm and recall policy.*One imaging technique only recommended in centers of excellence with high-end radiological equipment.**HCC radiological hallmark: arterial hypervascularity and venous/late phase washout

Mass/nodule on US

<1cm 1-2cm >2cm

4-phase CT or DynamicContrast enhanced MRI

4-phase CT/DynamicContrast enhanced MRI

Repeat US at 4 mo

Growing/ChangingCharacter

Stable

1 or 2 positive techniques*:HCC radiological Hallmarks**

1 positive technique:HCC radiological Hallmarks**

Yes No

HCC Biopsy

Investigate according to size

Inconclusive

Yes No

HCC Biopsy

Diagnostic algorithm

EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf

Treatment algorithm – AISF guidelines

* : each TACE; ** : with cTACE, MRI is preferred to CT *** : Response must be assessed by modified RECIST criteria

Position paper AISF DLD 2013 45(2013) 712-723

sorafenib

HCC not amenable to curative treatments

Child Pugh class A or B7Performance Status ≤1

No portal/hepatic vein invasion (except segmental or subsegmental

portal branches))

1st treatment(cTACE or DEB-TACE)

2nd treatment(cTACE or DEB-TACE)

MRI or CT** at 1 month

MRI or CT** at 1 month

No complete response

Partial response Newly developed HCC

Complete response

MRI or CT every 3 months

Desease recurrence

Consider another course of cTACE or DEB-TACE (and/or ablation techniques)

Liver failure orsevere adverse events*

Yes

No Resolution

Palliation

Desease progressionor stable desease

Systemic therapies – AISF guidelines

Position paper AISF DLD 2013 45(2013) 712-723

NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancer. V2.2013; Available from: www.nccn.org Accessed on 09-May 2013.

• Imaging every 3–6 months for 2 years, then every 6-12 months

• AFP, if initially elevated, every 3-6 months for 2 years, then every 6-12 months

• See relevant pathway (HCC-2 through HCC-7) if disease recursOptions:

• Sorafenib(Child–Pugh Class A [category 1] or B)

• Chemotherapy ± RT only in the context of a clinical trial Systemic chemotherapy Intra-arterial chemotherapy

• Clinical trial• Locoregional therapy• RT (conformal or stereotactic) (category 2B)• Supportive care

Options:• Sorafenib

(Child–Pugh Class A [category 1] or B)

• Clinical trial• Locoregional therapy• RT (conformal or stereotactic) (category 2B)• Supportive care

Options:

• Sorafenib(Child–Pugh Class A [category 1] or B)

• Supportive care • Clinical trial

SurveillanceTreatmentClinical presentation

• Refer to liver transplant center

• Consider brige therapy as indicated

Transplantcandidate

• Inadequate hepatic reserve

• Tumor location

Evaluate whether patient is a candidate for transplant (See UNOS criteria under Surgical Assessment HCC-5) Not a transplant

candidate

Extensive liver disease

Unresectable

Inoperable by perfomance status or comorbidity, local disease or local disease with minimal extrahepatic disease only

Metastatic disease or Extensive liver burden

Treatment algorithm – NCCN guidelines

Treatment algorithm - APASL guidelines

APASL recommendations on HCC, Omata M, et al. Hepatol Int. 2010;4:439–474

Sorafenib or systemic therapy trial

Confined to the liverMain portal vein

patent

HCC

Extrahepatic metastasisMain portal vein tumor

thrombus

Resectable

Child–Pugh A/B Child–Pugh C

Yes

No

Solitary tumor < 5 cm < 3 tumors < 3 cm

No venous invasion

Tumor > 5 cm > 3 tumors

Invasion of hepatic / portal vein branches

Child–Pugh A

Child–Pugh B

Child–Pugh C

Child–Pugh A/B

Child–Pugh C

Resection/RFA (for < 3 cm

HCC)

Local ablation Transplantation TACE Supportive care

Kudo et al. Dig Dis 2011;29:339–364

Consensus-based treatment algorithm - JSH

HCC

YesNo

Child-Pugh A/B Child-Pugh C Child-Pugh B/C Child-Pugh A

SorafenibPalliative care

*1, *2

YesNo

Exceeding Milancriteria

or age >65

Within Milan*7

criteriaor age ≤65

• Transplantation• TACE/ablation for Child-Pugh C Patient *10

• HAIC (Vp3,4)*8

• Sorafenib (vp3,4)*8

• TACE (Vp1,2)*9

• Resection(Vp1,2)*9

• TACE*5

• HAIC*5

• Resection*6

• Ablation*6

ResectionTACE• TACE+

Ablation*4

Sorafenib*5

(TACE refractory,child-pugh A)

• Resection• Ablation

• Intensive follow up

• Ablation

TREATMENT

SIZE

NUMBER

VASCULARINVASION

LIVER fUNCTION

EXTRAHEPATICSPREAD

No

Hypovascular

Early HCC*3

Single

Yes

1-3

≤3 cm >3 cm

≥4

Portal pressure/bilirubin

HCC

RFA Sorafenib

Stage 0PS 0, Child–Pugh A

Very early stage (0) 1 HCC < 2 cm

Carcinoma in situ

Early stage (A)1 HCC or 3 nodules

< 3 cm, PS 0

End stage (D)

Liver transplantation TACEResectionSymptomatic

treatment Curative treatments Palliative treatments

Associated diseases

YesNo

3 nodules ≤ 3 cm

Increased

Normal

1 HCC

Stage DPS > 2, Child–Pugh C

Intermediate stage (B)Multinodular,

PS 0

Advanced stage (C) Portal invasion, N1, M1, PS 1–2

Stage A–CPS 0–2, Child–Pugh A–B

PS, performance status; TACE, transarterial chemoembolization. Adapted from Bruix J, Sherman M. HEPATOLOGY, Vol. 53, No. 3, 2011. Available on: http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf

Treatment algorithm - AASLD guidelines

Portal pressure/bilirubin

HCC

PEI/RFA Sorafenib

Stage 0PS 0, Child–Pugh A

Very early stage (0) 1 HCC < 2 cm

Carcinoma in situ

Early stage (A)1 HCC or 3 nodules

< 3 cm, PS 0

End stage (D)

Liver transplantation TACEResection

Curative treatments (30%)5-year survival (40–70%)

Associated diseases

YesNo

3 nodules ≤ 3 cm

Increased

Normal

1 HCC

Stage DPS > 2, Child–Pugh C

Intermediate stage (B)Multinodular,

PS 0

Advanced stage (C) Portal invasion, N1, M1, PS 1–2

Stage A–CPS 0–2, Child–Pugh A–B

PS, performance status; TACE, transarterial chemoembolization; BSC, Best Supportive CareEASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.

Treatment algorithm – EASL, EORTC guidelines

Target: 40%OS: 11 mo (6-14)

Target: 20%OS: 20 mo (45-14)

BSC

Target: 10%OS: <3 mo

EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.

Systemic therapies – EASL, EORTC guidelines

Levels of evidence and grade of recommendation

Adjuvant therapy after resection

OLT-extended

Neoadjuvant therapy in waiting list

LDLT

Downstaging

Internal radiation Y90

Resection

Levels of evidence

(NCI)

Grade of recommendation(GRADE)

1

2

3

2 (weak) 1 (strong)

RF (<5 cm), RF/PEI (<2 cm)

Chemoembolization

External/palliative radiotherapy

Sorafenib

AC BAC B

OLT-Milan

EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf

Trial design strategies and control groups

EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711