Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma

Inclusion criteria

• Male and female patients, 21 to 80 years of age at the time of signature of the informed consent form.
• Histologically proven HCC after liver resection. Combined hepatocellular-cholangiocarcinoma can be included.
• HCC limited to the liver with no extra-hepatic metastasis on CT or MRI of the abdomen and chest (defined as lymph node <2 cm, lung nodules < 1 cm, farther lymph nodes < 2 cm) according to the AASLD criteria65.
• R0 or R1 resection on histology.
• Eligibility according to tumour size:

• Large tumour >= 5 cm (preferred)
• Smaller tumours >=2cm and < 5cm
• Multifocal tumours - maximum of 3 total tumours with size >=2cm detected from CT-scan. Detection of <1cm tumour intra-operatively or upon histologic examination following resection can be ignored. For multiple satellite nodules (>=2cm) that are detected intraoperatively, harvest ALL satellite nodules (>/= 2cm). DNA/RNA will be extracted from cases confirmed to be HCC/hepato-cholangiocarcinoma by histology. A MAXIMUM of 3 samples with the best quality are to be used for the analysis.
• Child-Pugh ≤ 7 points without clinical ascites before surgery.
• ECOG performance status 0-1 before surgery.
• Scheduled for liver resection within 6 weeks.
• The patient has received no anti-cancer specific treatment for HCC eg. previous liver resection, loco-regional therapy (e.g. RFA, TACE, SIRT), radiotherapy, immunotherapy, chemotherapy or neo-adjuvant chemotherapy other than the planned surgery. However, patient who has received previous HCC resection more than 5 years ago is deemed to have a de-novo liver tumour and therefore can be included.
• Adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria:

• Absolute neutrophil count ≥ 1.0 x 10^9/L
• Platelet count ≥ 50 x 10^9/L
• Haemoglobin ≥ 9.0 g/dL
• INR ≤ 2.0
• Serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN)
• Albumin ≥ 2.5 g/dL
• Total bilirubin ≤ 1.5 times the ULN
• Alanine transaminase (ALT) ≤ 2.5 times the ULN
• Aspartate transaminase (AST ≤ 2.5 times the ULN

Exclusion criteria

• Single lesion < 2 cm at the time of tumour resection.
• The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and highly likely to have been cured.
• Encephalopathy
• The patient has received a major organ allograft.
• The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
• The patient has an uncontrolled bleeding disorder.
• The patient has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia at the time of enrolment.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
• The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• The patient has received any investigational or non-registered medicinal product (drug or vaccine) within the 30 days preceding the date of enrolment, or plans to receive such a drug during the study period.
• For female patients: the patient is pregnant or lactating.
• Insufficient DNA/RNA for genome analysis at baseline
• Insufficient cells for immunology analysis at baseline (Singapore sites only)