LOCOREGIONAL THERAPY (LRT)–ABLATION,CHEMOEMBOLIZATION

AND HEPATIC ARTERY EMBOLIZATION

COLDA 2019DR BENJAMIN SARKODIE

UNIVERSITY OF GHANA MEDICAL SCHOOL

MANAGEMENT OF HCC

• Surgery is regarded as the standard of treatment and is potentially curative for HCC patients with preserved liver function;

• <15% are candidates for surgical resection at presentation due to cirrhosis, inadequate hepatic reserve, multiple lesions, anatomic constraints of the tumor and other comorbidities.

• Intrahepatic recurrence occurs among 68-96% of patients. • Liver transplantation is another treatment option especially

for patients with decompensated cirrhosis. • Systematic chemotherapy was found to have little impact

on survival, and negative impact on the health-related quality of life due to the toxicity to other organs and systems (Ibrahim 2008, Bult 2009, Riaz 2009, Zhou 2009).

• The limited treatment options for patients with unresectable HCC have led to the emergence of other liver directed therapies including:

• Ablative techniques Radiofrequency ablation/Microwave Ablation, Percutaneous ethanol injection (PEI), Cryoablation, Local administration of cytostatic drugs,

AndIntrarterial embolization techniques such as selective intrarterial radioembolization therapy, transarterial embolization (TAE), and transarterialchemoembolization (TACE).

Factors to consider in the management of HCC

• Access to Healthcare-

Available facilitities

Available skill/HR –Surgeons,IRs,Hepatologist

• Stage of HCC

• Performance Status

TREATMENT ALGORITHM

Management

CURATIVE• Ablation• Resection• TransplantationPALLIATIVE• TACE/Bland Embolization• Systemic Therapy-Sorafenib• Best Supportive Care• Radioembolization

Which way?EPL or the EL

ABLATION

• Image-guided percutaneous ablation is considered best in the treatment of early-stage hepatocellularcarcinoma (HCC).

• Ablation is potentially curative, minimally invasive, and easily repeatable for recurrence.

RFA

• RFA has recently been the most prevailing ablation technique for HCC .

• RFA treatments, with a median follow-up of 38.2 months, survival rates were 60.2 % and 27.3 % at 5 and 10 years, respectively .

• Local tumor progression rates after RFA were 2.4–27.0% .

• Mortality and Morbidity of RFA were 0.9–7.9% and 0–1.5%, respectively.

Shiina S. Et al Am J Gastroenterology.2012

The Microwave Gadget

MWA

• Treatment efficacy of MWA is less affected by heat sink effect (vessels near the treated region) compared with that of RFA.

• Recent studies have further suggested that MWA may be more effective than RFA for large HCC.

• MWA has several advantages over other local treatment options such as an

❑Consistently higher intra tumoral temperatures

❑Larger ablation volumes

❑Faster ablation times

❑Option of using multiple antennae simultaneously

Francesco Izza et al The Oncologist June 2019

PROCEDURE

• Standard pre-operative evaluation of patients include a triple phase computed tomography (CT) scan of the abdomen, abdominal ultrasound, laboratory investigations, including; liver enzymes (ALT, AST), serum albumin, coagulation profile (PT, PTT, INR), serum creatinine and complete blood picture

PROCEDURE

• CT images are reviewed .A suitable trajectory is chosen during on table abdominal USG and local anaesthesia administered.A pre-incision of the skin is done and an antenna is inserted and positioned at the designated place of the tumor under sonographic guidance

NONCONTRAST POST CONTRAST

FINAL NEEDLE POSITIONABLATION IN PROGRESS

• Before treatment, a detailed plan for the placement of the electrode,

the power output setting, and the Ablation time are established on a tumor-by-tumor basis.

• The aim of the treatment is to completely destroy the tumor, as well as the surrounding 0.5–1.0 cm normal appearing liver tissue.

• In general a high power for a low time is used, i.e., an output setting of 55 W for 6min.

• In the lesions > 3 cm, after the first application the treatment is stopped, then the needle is moved a bit backward, change direction of re-insert into the tumor, and start a further treatment session. This maneuver is repeated 2 times to ensure a bigger dimension of necrosis.

• During each application of microwave energy, an expanding hyperechogenic area is produced which roughly judges the size of the ablation zone, i.e., necrotic zone.

Assessment of therapeutic efficacy

• Local therapeutic efficacy is evaluated by contrast enhanced dynamic CT scanning at 1 month after treatment and serum alpha feto protein levels for those who have elevated alpha fetoprotein levels prior to ablation.

• Complete ablation is defined as uniform hypo-attenuation without enhancement in the previous tumor area .

• Contrast enhancement in the ablated zone indicated incomplete ablation or local recurrence when detected later on imaging. Technical success is defined as complete ablation of the tumor, as determined at CT performed 1 month after Ablation .

CONCLUSION:

• Ablation is an exciting technique and a very effective treatment modality for early stage HCC. Low incidence of complications.

• Screening of at risk group and early detection of HCC should be encouraged so ablative therapy can be encouraged.

The rationale of TACE• Regional therapy stems from the difference in the

dual blood inflow supply via the portal vein and hepatic artery between normal liver parenchyma and HCC.

• Normally the portal vein is responsible for supplying most (75-85%) of the blood to the liver, and the hepatic artery providing only a supportive role (15-25%). This balance is greatly altered in HCC in which the hepatic artery becomes the sole (90- 100%) supply of the tumor. The regional therapies for HCC make use of this configuration and use the hepatic artery as a roadway to treat the tumor with less effect on the nontumorousliver (Zhou 2009, Shin 2009).

Technique

• Standard Pre-Op preparations

• Review Images

• Sterile Angio room

• CFA/Brachial/Radial puncture

• Selective SMA and Celiac angiograms

• Chemo+Embolization

• Secure Hemostases

• TACE has also been used as a neoadjuvant therapy with a hope of reducing tumor size; inducing tumor necrosis, and preventing dissemination during surgery of resectable HCC cases.

• According to the guidelines published by the American association for Study of Liver Disease (AASLD) and the European Association for the Study of the Liver (EASL), TACE is recommend as a first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread

• TACE involves mixing cytotoxic agents such as doxorubicin, cisplatin, mitomycin C with lipiodol and administering it into the feeding artery of the tumor. This is followed by transarterial embolization to block blood flow to the supplying artery. Lipiodol selectively remains in tumor nodules for several weeks to over a year.

• TACE thus has both selective ischemic and therapeutic effects on HCC;the embolotherapy interrupts the arterial blood flow to the tumor inducing its ischemic necrosis, and prevents washout of the administered chemotherapeutic agents which will remain in the tumor for a longer period at a higher concentration. Embolotherapy + regional chemotherapy has synergetic, antitumor effects with lower systemic drug levels, less toxicity, and minimal damage to liver.

(Lau 2008, Shin 2009).

• Commonly used embolic agents include gelatin sponges, polyvinyl alcohol particles (PVA), microspheres, and steel coils.

• These agents have different characteristics, can be prepared in different sizes, some embolizepermanently, and others embolize temporarily.

• There is also no standardized protocol in the choice of the degree of embolization, chemotherapeutic drug, dosage, dilution, rate of injection, number of treatments, or interval between courses of therapy. (Jansen 2005, Lau 2008, Shin 2009)

Absolute contraindications

• Intractable systemic infection, Child –Pugh C, or the presence of hepatofugal portal flow.

• Others: cardiac or renal failure, severely impaired liver function, clinically relevant ascites, significant thrombocytopenia, portal vein thrombosis, or patients with a transjugular intrahepatic portosystemic shunt (Maleux 2009).

COMPLICATIONS :• Post embolization syndrome (PES) occurs

among >50% of cases; right upper quadrant pain, nausea, vomiting, and fever with elevated liver enzymes.

• Recovery from these symptoms usually takes place within 7-10 days. Others: thrombosis and occlusion, site infection, mesenteric ischemia, and more rarely tumor rupture, active liver failure, gallbladder necrosis, liver abscess, and pulmonary lipiodol embolism (Jansen 2015).

• TACE vs. conservative/suboptimal management of unresectable HCCStatistically significant positive impact of TAE/TACE on survival in selected patients with preserved liver function was shown in two RCTs conducted in the early 2000s; one in Barcelona (Llovet 2002) that compared either TAE or TACE to conservative therapy, and another in Hong Kong (Lo 2002) that compared TACE to conservative measures, as well as two meta- analyses (Camma 2002 and Llovet 2003) that pooled the results of these two trials with a number of earlier RCTs that also compared TAE/TACE to conservative/ suboptimal therapy.

• Llovet and colleagues’ (2003) meta-analysis of 7 RCTs (545 patients) showed a 2-year survival of 41% among patients treated with TAE / TACE and 27% among those who received a conservative or suboptimal management of HCC (odds ratio 0.53, p= 0.017). The meta-analysis pooled the results of trials using either TAE or TACE. A sensitivity analysis performed by the authors indicated a significant benefit with chemoembolization

CASE• 56 years old Ghanaian male• H/O HBV cirrhosis• known HBV > 10 years• FU on lamivudine • US abdomen (11/4/2018) Liver cirrhosis with a stable

hypoechoic lesion in the segment 4b . New hypoechoic nodule in the left lobe of the liver

• CT liver (3/5/2018) Liver cirrhosis. There is a 1.7 cm hypervascular lesion in the left hepatic dome demonstrating washout and delayed capsular enhancement, in keeping with a hepatoma.. The portal vein and hepatic veins are patent

USG

CT

TECHNIQUE

• Standard Pre-Op preparations

• Review Images

• Sterile Angio room

• CFA/Brachial/Radial puncture

• Selective SMA and Celiac angiograms

• Chemo+Embolization

• Secure Hemostases

CELIAC,CHA ANGIO

CHA ANGIO

Post TACE CT

STRATEGIES GOING FORWARD

• Cooperation among Physicians- MDT

• Training for more Physicians to be able to offer TAT

• Awareness Creation

• Screening And Surveillance of at Risk population

• Early Detection and Treatment

• National Policy and Direction

• Research And Development

• Partnerships with other countries

Thank you for listening