ECOG performance status 14
0 Fully active ; able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2 Ambulatory and capable of all self-care but unable to carry out work activities ; up and about more than 50 % of waking hours
3 Capable of only limited self-care ; confined to bed or chair more than 50 % of waking hours
4 Completely disabled ; cannot carry out any self-care ; totally confined to bed or chair
comorbidities . 16 , 17 All patients should therefore be discussed in a multi-disciplinary tumour board ( including liver and transplant surgeons ). Management can be either surgical or non-surgical .
Surgical management Hepatic resection Surgical resection for HCC is a recommended treatment option in patients with a normal bilirubin level and without clinically significant portal hypertension , in the very early stages ( BCLC stage 0 ) and with a single HCC nodule < 2cm ). Significant portal hypertension was defined as a hepatic venous pressure gradient ≥10mmHg and practically assessed by the presence of ascites , oesophageal varices or a platelet count < 100,000 / mm3 associated with clinically significant splenomegaly . 18
R0 liver resection is recommended for a single tumour in patients with well-preserved liver function . Child-Pugh A patients without significant portal hypertension are considered good candidates for minor / major liver resections . Carefully selected patients with Child-Pugh B and / or portal hypertension may be candidates for minor surgical resections . Child-Pugh C patients are not candidates for surgical resection . Surgical resection is a potentially curative treatment , but almost 70 % of patients develop recurrent HCC 5 years after resection . 19
Liver transplantation Liver transplantation is the most definitive treatment option for HCC ( see full chapter later in this handbook )
Recommended for patients meeting the MILAN criteria ( single tumour < 5cm in diameter ; no more than three tumour nodules not exceeding 3cm ; no extrahepatic involvement or angioinvasion ) 20 and where less than 10 % recurrence and 70 % survival at 5 years survival is expected . The availability of livers for transplant is a major limitation and in situations where the waiting time exceeds three months , patients can be offered bridging resection , local ablation , or transarterial chemoembolism ( TACE ). 11
Non-surgical management While surgical treatment is considered to be the better option for the treatment of HCC , many patients have unresectable disease upon presentation . Non-surgical techniques include thermal T ablation , radiotherapy techniques and TACE .
Thermal T ablation Imaged-guided percutaneous local ablation is one of the best choices for non-surgical patients with early-stage HCC . Several methods are available for thermal ablation of tumours and localised heating or freezing allows for destruction of the malignant tumour while at the same time , preserving the normal liver parenchymal tissue . Thermal ablation modalities include radiofrequency ( RFA ) or microwave ablation ( MWA ) and are considered as first-line treatment options for very early-stage ( BCLC 0 ) HCC . 11 RFA is an alternative first-line option for early-stage HCC ( up to 3 lesions up to 3cm ).
Radiotherapy Eligibility criteria for radiotherapy include :
• Ineligible for transplant .
• Ineligible for RFA / MWA / TACE due to technical reasons .
• After RFA / MWA / TACE if there is a recurrence of residual disease . 11
Stereotactic body radiotherapy ( SBRT ) is an advanced technique that delivers large ablative doses of radiation . 11 SBRT ( typically 3 – 5 fractions ) is often used for patient with 1 – 3 tumours and could be considered for larger lesions or more extensive disease , if there is sufficient uninvolved liver and liver radiation tolerance can be respected .
TACE TACE is recommended for patients with a relatively wellpreserved liver function , and no evidence of vascular invasion or extrahepatic spread , i . e ., patients with intermediate-stage disease based on the BCLC system . The process involves two main steps – intra-arterial infusion of cytotoxic chemotherapy and delivery of embolisation particles , which results in necrosis of the tumour . 21 TACE is the most commonly used locoregional treatment in patients listed for liver transplantation to prevent tumour progression . Conventional lipiodol-based TACE prolongs the overall survival of BCLC A to intermediate BCLC B asymptomatic patients with maintained liver function and a small tumour burden . Doxorubicin-eluting bead ( DEB ) -TACE is an option to reduce the side effects of the chemotherapy . 11 The combination of TACE with systemic agents such as sorafenib , either sequentially or at the same time , is not recommended for clinical practice . 11
Fig 1 summarises treatment options depending on BCLC stage of early / intermediate HCC
Perioperative albumin treatment The liver is the sole source of endogenous albumin and the presence of liver cancer and liver-related lesions greatly reduce albumin synthesis . Moreover , serum albumin levels are lower in patients undergoing surgical treatment due to both bleeding and increased vascular permeability as a consequence of postoperative tissue trauma , leading to albumin leakage into tissue fluid .
Preoperative serum albumin level is considered an important indicator of the postoperative prognosis in liver cancer patients . A 2021 meta-analysis of the association between serum pre-albumin levels and prognosis in HCC patients undergoing hepatectomy , concluded that low pre-albumin levels were significantly associated with an adverse prognosis . 22 Albumin levels are also an important factor in relation to post-operative intra-abdominal infection ( IAI ). In a retrospective study of patients undergoing major hepatectomy , IAI occurred in 14.6 % of patients and the
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