Anti-Tumour TreatmentLocoregional radiological treatment for hepatocellular carcinoma; Which, when and how?
Section snippets
Review criteria
PubMed was searched from March to July 2010 for full-text papers published in English language journals, using the keywords “Hepatocellular carcinoma”, “Liver Cancer”, “Locoregional treatments”, “Percutaneous ethanol injection”, “Radiofrequency ablation”, “Transarterial chemoembolization”, “Transarterial radioembolization”, and “Transarterial chemoembolization with drug-eluting bead”. Also, important abstracts presented in the most recent International Meetings (American Society of Clinical
Percutaneous ethanol injection and radiofrequency ablation
Percutaneous ablation is the best therapeutic modality for patients with HCC who are not candidates for surgical resection or liver transplantation. Liver cancer cells can be destroyed by chemical substances, such as alcohol and acetic acid; or by modifying neoplastic cells temperature with radiofrequency, microwaves, laser, or cryoablation.
In patients who received PEI the distribution of ethanol may be blocked by the intratumoral fibrotic septa and/or the tumor capsule, resulting in a
Summary for percutaneous ablation therapy
RFA is the standard percutaneous ablation treatment for patients with HCC and preferentially for lesions ⩽3 cm (single or up to 3 lesions), and single lesion ⩽5 cm who are not candidates for liver resection or liver transplant; with well preserved liver function (Child-Pugh A or B) and good performance status (BCLC Stage A–C, Eastern Cooperative Oncology Group [ECOG] status 1–2). Recommendation grade A.
PEI should be reserved only when RFA is not available or not technically possible
Transarterial chemoembolization with lipiodol (conventional TACE)
Conventional TACE is the primary treatment used most frequently for unresectable HCC, but is not recommended in early stages as a first option. At very early stage the HCC is not highly vascularized and its main blood supply comes from the portal vein, but as the HCC grows its blood supply comes from the hepatic artery. This feature provides the basis of arterial obstruction as an effective treatment for HCC.
Embolization of the hepatic artery with the appropriate technique may induce extensive
TACE with drug-eluting bead
TACE with DC bead is a novel drug delivery embolization system, comprising biocompatible, nonresorbable polyvinyl alcohol polymeric microspheres doped with sulfonyl groups resulting in a static charge leading to reversible ionic binding with polar molecules such as doxorubicin. In a similar fashion a second type of superabsorbent polymer microsphere, consisting of an acryl-amine polymer also possess static charge and the ability to ionically load doxorubicin. The bed’s high affinity for the
Summary for conventional TACE and TACE with DC bead
Conventional TACE is the standard treatment for solitary lesions <8 cm or multinodular tumors (>3 lesions), with no evidence of extrahepatic disease (visceral or lymph node metastasis), in patients with well preserved liver function (Child-Pugh A and B) and performance status (ECOG 0–2, BCLC A–C). Recommendation grade A.
TACE with DC bead may be an option as well, particularly in patients with more advanced liver disease (Child Pugh B, ECOG 2, BCLC C, bilobar or recurrent disease) or patients
Transarterial radioembolization
External beam irradiation has historically played a limited role in the treatment of HCC due to the radiosensitive nature of normal hepatic tissue. Liver exposure to radiation doses greater than 40 Gray (Gy) units may result in a clinico-pathological syndrome characterized by ascites, anicteric hepatomegaly, and elevated liver enzymes, developing weeks to months following therapy. This has been called radiation induced liver disease (RILD) or radiation hepatitis and is characterized
Summary for TARE
TARE has shown promising results in phase II trials for locally advanced HCC; therefore RCT in comparison to conventional TACE/drug-eluting beads are needed. TARE therapy appears to be safe in more advanced disease including portal vein invasion and larger tumors. Recommendation grade B.
Tumor response assessment after TARE should be done 1 month after treatment, and subsequent evaluations should be performed every 3 months. Recommendation grade B.
Combination of locoregional treatments
TACE combined with other therapies has not been considered in any treatment algorithms for HCC; although several randomized and non-randomized trials as well as meta-analysis have addressed this point. TACE appears to decrease tumor resistance to perfusion with ethanol and can disrupt intratumoral septa via tumor necrosis, consequently, facilitating ethanol diffusion into the lesion. Embolization may also reduce ethanol wash out of the tumor enhancing its toxic effect; additionally,
Summary for combination of local treatments
Combination therapy with RFA/PEI + TACE may be an option for patients with single lesions > 3 cm and <8 cm, with well preserved liver function (Child-Pugh A and B) and performance status (BCLC A–C, ECOG 0–2). Recommendation grade B.
How to evaluate the response to locoregional therapies
The evaluation of response to locoregional therapies is essential, as an objective response may become a surrogate marker for improved survival. Criteria have been developed for response assessment, including the World Health Organization (WHO)[49], [50], the Response Evaluation Criteria in Solid Tumors (RECIST),[51], [52] and the European Association for the Study of the Liver Criteria (EASL)53 (Table 4). However, there are limitations of these criteria, for example WHO and RECIST evaluates
Summary for treatment response
The evaluation of tumor response after radiological locoregional therapies should consider identification of intra-tumoral necrotic areas and reduction of tumor load identified by CT or MRI. The evaluation of tumor response should not include only the reduction of overall tumor size. EASL and mRECIST criteria should be used preferentially as these classifications capture the extent of the necrosis, instead of only the reduction in tumor size. Recommendation grade B.
Patients with high AFP before
Conclusions
Liver transplantation and surgical resection remain as treatments of choice for patients with HCC, if feasible. Randomized controlled trials favor the use of RFA as first-line treatment in patients with small HCC, and adequate hepatic function only when surgery and liver transplantation are not a viable option, and in some cases percutaneous ablation treatments (RFA and PEI) can be used as bridge towards liver transplantation, especially in patients with waiting times longer than 6 months.
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