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HCC Guidelines and recommendation 2013. Diagnostic algorithm. New mass/ nodule. Ø < 1cm. Ø ≥1cm. US 3 months. TC/RM/CEUS*. Increase ( Ø ≥ 1 cm). Typical feature (wash in/wash out). No. Yes. No. Yes. US 3 months (for 12 months ). Alternative imaging technique. Yes.
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Diagnostic algorithm New mass/nodule Ø < 1cm Ø ≥1cm US 3 months TC/RM/CEUS* Increase (Ø ≥ 1 cm) Typicalfeature (wash in/wash out) No Yes No Yes US 3 months (for 12 months) Alternative imagingtechnique Yes Increase (Ø ≥ 1 cm) Atypicalfeature Typicalfeature No Biopsy US 6 months Otherdiagnosis Inconclusive HCC US, Ultrasound; MRI, Magneticresonanceimaging; CT, computedtomography; CEUS, contrast-enhancedultrasonography *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 Mass/nodule on US <1cm 1-2cm >2cm 4-phase CT/Dynamic Contrast enhanced MRI 4-phase CT or Dynamic Contrast enhanced MRI Repeat US at 4 mo 1 or 2 positive techniques*: HCC radiological Hallmarks** 1 positive technique: HCC radiological Hallmarks** Growing/Changing Character Stable Yes No Yes No Investigate according to size HCC HCC Biopsy Biopsy Inconclusive 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 EASL–EORTC ClinicalPracticeGuidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf
Treatment algorithm – AISF guidelines HCC notamenable to curative treatments No portal/hepaticveininvasion (exceptsegmental or subsegmentalportalbranches)) Child Pughclass A or B7 Performance Status ≤1 1sttreatment (cTACEor DEB-TACE) Liverfailureor severe adverseevents* MRI or CT** at 1 month Complete response Resolution No No complete response Yes Palliation MRI or CT every 3 months 2ndtreatment (cTACEor DEB-TACE) Deseaseprogression or stabledesease Deseaserecurrence MRI or CT** at 1 month Partialresponse Newlydeveloped HCC Consider another course of cTACE or DEB-TACE (and/or ablation techniques) sorafenib * : 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
Systemic therapies – AISF guidelines Position paper AISF DLD 2013 45(2013) 712-723
Treatment algorithm – NCCN guidelines Clinical presentation Treatment Surveillance • Refer to liver transplant center • Consider brige therapy as indicated • 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 recurs Transplantcandidate Evaluate whether patient is a candidate for transplant (See UNOS criteria under Surgical Assessment HCC-5) • Inadequate hepatic reserve • Tumor location Not a transplant candidate • Options: • 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 Unresectable Extensive liver disease • Options: • Sorafenib(Child–Pugh Class A [category 1] or B) • Clinical trial • Locoregional therapy • RT (conformal or stereotactic) (category 2B) • Supportive care Inoperable by perfomance status or comorbidity, local disease or local disease with minimal extrahepatic disease only • Options: • Sorafenib(Child–Pugh Class A [category 1] or B) • Supportive care • Clinical trial Metastatic disease or Extensive liver burden NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary Cancer. V2.2013; Available from: www.nccn.orgAccessed on 09-May 2013.
Treatment algorithm - APASL guidelines HCC Confined to the liver Main portal vein patent Extrahepatic metastasis Main portal vein tumor thrombus Resectable Child–Pugh A/B Child–Pugh C Sorafenib or systemic therapy trial Yes No Solitary tumor < 5 cm < 3 tumors < 3 cm No venous invasion Tumor > 5 cm > 3 tumors Invasion of hepatic / portal vein branches Resection/RFA (for < 3 cm HCC) Child–Pugh A Child–Pugh B Child–Pugh C Child–Pugh A/B Child–Pugh C Local ablation Transplantation TACE Supportive care APASL recommendations on HCC, Omata M, et al. Hepatol Int. 2010;4:439–474
Consensus-based treatment algorithm - JSH HCC EXTRAHEPATIC SPREAD No Yes LIVER fUNCTION Child-Pugh A/B Child-Pugh C Child-Pugh B/C Child-Pugh A VASCULAR INVASION No Yes No Yes Single *1, *2 ≥4 1-3 NUMBER Within Milan*7 criteria or age ≤65 Exceeding Milan criteria or age >65 Hypovascular Early HCC*3 ≤3 cm >3 cm SIZE TREATMENT • Intensive • follow up • Ablation • Resection • Ablation • Resection • TACE • TACE+ • Ablation*4 • TACE*5 • HAIC*5 • Resection*6 • Ablation*6 • HAIC (Vp3,4)*8 • Sorafenib (vp3,4)*8 • TACE (Vp1,2)*9 • Resection(Vp1,2)*9 • Transplantation • TACE/ablation • for Child-Pugh C • Patient *10 Palliative care Sorafenib Sorafenib*5 (TACE refractory,child-pugh A) Kudo et al. Dig Dis 2011;29:339–364
Treatment algorithm - AASLD guidelines Symptomatictreatment HCC Stage 0PS 0, Child–Pugh A Stage A–CPS 0–2, Child–Pugh A–B Stage DPS > 2, Child–Pugh C Very early stage (0) 1 HCC < 2 cmCarcinoma in situ Early stage (A) 1 HCC or 3 nodules< 3 cm, PS 0 Intermediate stage (B) Multinodular,PS 0 Advanced stage (C) Portal invasion, N1, M1, PS 1–2 End stage (D) 1 HCC 3 nodules ≤ 3 cm Portal pressure/bilirubin Increased Associated diseases Normal No Yes Resection Liver transplantation RFA TACE Sorafenib Curative treatments Palliative treatments 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 – EASL, EORTC guidelines HCC Stage 0PS 0, Child–Pugh A Stage A–CPS 0–2, Child–Pugh A–B Stage DPS > 2, Child–Pugh C Very early stage (0) 1 HCC < 2 cmCarcinoma in situ Early stage (A) 1 HCC or 3 nodules< 3 cm, PS 0 Intermediate stage (B) Multinodular,PS 0 Advanced stage (C) Portal invasion, N1, M1, PS 1–2 End stage (D) 1 HCC 3 nodules ≤ 3 cm Portal pressure/bilirubin Increased Associated diseases Normal No Yes Resection Liver transplantation PEI/RFA TACE Sorafenib BSC Curative treatments (30%) 5-year survival (40–70%) Target: 20% OS: 20 mo (45-14) Target: 40% OS: 11 mo (6-14) Target: 10% OS: <3 mo PS, performance status; TACE, transarterialchemoembolization; BSC, Best Supportive Care EASL–EORTC ClinicalPracticeGuidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
Systemic therapies – EASL, EORTC guidelines EASL–EORTC ClinicalPracticeGuidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf.
Levels of evidence and grade of recommendation 1 Levels of evidence(NCI) Sorafenib Chemoembolization RF (<5 cm), RF/PEI (<2 cm) Adjuvant therapy after resection Resection OLT-Milan 2 LDLT Internal radiation Y90 OLT-extended Neoadjuvant therapy in waiting list Downstaging 3 External/palliative radiotherapy C B A C B A 1 (strong) 2 (weak) Grade of recommendation (GRADE) EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma Journal of Hepatology 2012 vol. 56 j 908–943 Available 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 908–943 Available on: http://www.easl.eu/assets/application/files/d38c7689f123edf_file.pdf Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711