TX For Hepatocellular

Carcinoma(HCC)
Dr Alex Mogere
Consultant Physician
Overview
• Most HCC pts have 2 liver diseases, cirrhosis and HCC, each of which
is an independent cause of death
• The presence of cirrhosis usually places constraints on resection
surgery, ablative therapies, and chemotherapy
• Pts presenting with advanced tumors (vascular invasion, symptoms,
extrahepatic spread) have a median survival of ∼4 months, with or
without Tx
• Needs a multidisciplinary team: hepatologist, interventional
radiologist, surgical oncologist, resection surgeon, transplant surgeon,
and medical oncologist
HCC Tx Algorithm
Defn of terminologies on tx algorhythm
• AFP, α fetoprotein;
• LN, lymph node;
• MWA, microwave ablation;
• OLTX, orthotopic liver transplantation;
• PEI, percutaneous ethanol injection;
• RFA, radiofrequency ablation;
• TACE, transcatheter arterial chemoembolization;
• UNOS, United Network for Organ Sharing.
• Child’s A/B/C refers to the Child-Pugh classification of liver failure
Tx options available
Surgical excision
• Most successful in pts with small tumors(< 5 cm) and with good LFT
• Hepatectomy- section of the liver is excised, if tumor is ltd to a section
• Liver transplantation is ltd to Ca confined to the liver, if a suitable
donor is found: must fulfill strict criteria
Negative prognostic factors
• Tumor size
• Cirrhosis
• Infiltrative growth pattern
• Intrahepatic mets
• Vascular invasion
• Multifocal tumors
• Lymph node mets
• Margin < 1 cm
• Lack of a capsule
Liver Transplantation
• A viable option for stages I and II tumors in the setting of cirrhosis
• OLTX for pts with a single lesion ≤5 cm or 3 or fewer nodules, each ≤3
cm (Milan criteria), resulted in excellent tumor-free survival (≥70% at
5 years)
• For advanced HCC, OLTX has been abandoned due to high tumor
recurrence rates
• Pretransplant therapies used as a “bridge” to OLTX, including RFA,
TACE, and hepatic arterial 90Y-radioembolization
Cont.Liver Transplantation
Milan Criteria
Current directions -Transplantation
• Expanded milan criteria for larger HCCs beyond the Milan criteria
(one lesion <5 cm or three lesions, each <3 cm), such as the University
of California, San Francisco (UCSF) criteria (single lesion ≤6.5 cm or
two lesions ≤4.5 cm with a total diameter ≤8 cm; 1- and 5-year
survival rates of 90 and 75%, respectively), are being increasingly
accepted by various UNOS areas for OLTX with satisfactory longer-
term survival comparable to Milan criteria results
Ct current directions : transplantation
• Within-criteria patients with AFP levels >1000 ng/mL have
exceptionally high postOLTX recurrence rates.
Adjuvant therapy
• The role remains unclear
• Adjuvant and neoadjuvant approaches: no clear advantage in disease-
free or overall survival has been found
• Antiviral tx, instead of anticancer tx, has been successful in decreasing
postresection tumor recurrences in the postresection adjuvant
setting.
• Nucleoside analogues in HBV-based HCC and peg-interferon plus
ribavirin for HCV-based HCC have both been effective in reducing
recurrence rates
Local ablation therapies
• Routes: percutaneous, laparascopy , open(percutaneous best choice
for early stage tumor who aren’t surgical candidates)
• RFA uses heat to ablate tumors
• The max size of the probe arrays allows for a 7-cm zone of necrosis,
which would be adequate for a 3- to 4-cm tumor.
• Tx of tumors close to the main portal pedicles can lead to bile duct
injury and obstruction
Selection criteria: local ablation
• Single tumor < 5 cm
• Multiple tumors < 3 nodule and < 3cm
• No evidence of vascular invasion
• No extrahepatic spread
• Performance status- 0
• Cirrhosis with Child Pugh Class A or B
Percutaneous method
A- chemical ablation
• Ethanol injection
• Acetic acid injection

B- Thermal ablation
• RFA
• Microwave
• Laser ablation
• cryoablation
Chemoembolization
Radiation Tx
Tx Stages III&IV
• Fewer surgical options exist for stage III tumors involving major
vascular structures
• The prognosis is poor for stage IV tumors, and no surgical treatment
is recommended.
Systemic chemotx
• No single agent or combination of agents given systemically
reproducibly leads to even a 25% response rate or has any effect on
survival.
Regional chemotx
• A variety of agents given via the hepatic artery have activity for HCC
confined to the liver
Some randomized ClinicaL trials involving transhepatic artery Chemoembolization
(tace) for hepatocellular Carcinoma
Kinase inhibitors
• A survival advantage has been observed for the oral multikinase
inhibitor, sorafenib (Nexavar), versus placebo in two randomized trials
• It targets both the Raf mitogenic pathway and the vascular endothelial
growth factor receptor (VEGFR) endothelial vasculogenesis pathway.
• Sorafenib has considerable toxicity, with 30–40% of pts requiring “drug
holidays,” dose reductions, or cessation of tx
• The most cmn toxicities:fatigue, hypertension, diarrhea, mucositis, and
skin changes eg.the painful hand-foot syndrome, hair loss, and itching,
each in 20–40% of pts
• Other targeted txs failed their trials
Novel medical Txs for HCC
Summary of Mx HCC
Cont. summary of Mx HCC
Therapy
HCC <2 cm: RFA, PEI, or resection
HCC >2 cm, no vascular invasion: liver resection, RFA, or OLTX
Multiple unilobar tumors or tumor with vascular invasion: TACE or
sorafenib
Bilobar tumors, no vascular invasion: TACE with OLTX for patients
with tumor response
Extrahepatic HCC or elevated bilirubin: sorafenib or bevacizumab plus
erlotinib (combination agent trials are in progress)
THANK YOU!