cTACE

Conventional TranArterial ChemoEmbolization (cTACE) for HCC

cTACE treatment involves the introduction of a cytotoxic drug, such as doxorubicin, epirubicin, idarubicin, mitomycin C, or cisplatin, which is mixed with the oily radio-opaque agent Lipiodol (Lipiodol® Ultra-Fluid, Guerbet), and injected directly into the affected artery. This is followed by the administration of an embolic agent, such as gelatin sponge, polyvinyl alcohol particles, or microspheres, through the same artery. The Lipiodol carries the chemotherapy to the tumor site, delivering the drugs directly to the cancer cells while also causing the tumor’s blood supply to be cut off due to embolization. The presence of Lipiodol in the tumor, as detected on post-procedure CT scans, has been linked to improved overall survival rates. As a result of these findings, cTACE has been widely recognized as the gold standard treatment for intermediate stage HCC, earning the highest grade of recommendation (1A) in 2012.

Case video and description:

A. Introduction: This video presents a detailed case report of an elderly female patient diagnosed with Hepatitis C Virus (HCV)-related Chronic Liver Disease (CLD) and a single large Hepatocellular Carcinoma (HCC) tumor with a size larger than 8 cm. The case highlights the therapeutic approach and management strategies in a complex clinical scenario.

B. Patient Profile: Age/Gender: Elderly Female Medical History: HCV-related CLD Diagnosis: Single large HCC (more than 8 cm in size), Lung lesion seen on MR imaging was confirmed to be of non-malignant etiology on PET-CT (images not shown) which resolved after 2 weeks of medical management.

C. Clinical Assessment: CHILD B Score: 7 ECOG Performance Status: 0 (fully active, able to carry on all pre-disease activities without restriction) STATE Score: Greater than 18, indicating feasibility for cTACE

D. Management and Treatment: Initiation of Lenvatinib Therapy: The patient was started on lenvatinib, a multi-kinase inhibitor that has shown efficacy in treating HCC. Lenvatinib is known for its ability to target tumor angiogenesis and proliferation. Combination Therapy with cTACE: Two weeks post-initiation of lenvatinib, the patient underwent conventional Transarterial Chemoembolization (cTACE). This decision was based on the tumor size and the patient’s overall condition. cTACE involves the direct delivery of chemotherapeutic agents (lipiodol mixed doxorubicin) to the liver tumor, combined with embolization with PVA particles that restricts the tumor’s blood supply.

E. Discussion: This case is significant due to the complexity of managing a large HCC in an elderly patient with underlying liver disease. The combination of lenvatinib and cTACE represents an integrated approach targeting both the tumor’s growth and its blood supply. The patient’s good performance status (ECOG 0) was a key factor in opting for this aggressive treatment strategy.

F. Conclusion: The case underscores the importance of a tailored approach in the management of HCC, especially in elderly patients with comorbidities. It highlights the need for a multidisciplinary team to assess and plan the treatment course in such complex scenarios.

Keypoints:

Steps	Recommendations
Patient Selection	Tumor Burden and Staging, Liver Function and Performance Status are assessed. Scoring system like STATE score and HAP score can be used (Predicting Response to First TACE).
Pre-Procedure Imaging	Triple Phase Computed Tomography or Dynamic Contrast Enhanced Magnetic Resonance Imaging is performed prior to treatment allocation
Patient Preparation	Discuss Antiemetic treatment, Intravenous hydration, Analgesic management, and Antibiotic Management.
Role of Cone Beam CT	Cone Beam CT can be performed for tumor visualization, targeting, and assessment of treatment completion
Assessment of Extrahepatic vascular supply to HCC (- Tumor size > 5cm, - Tumor Location near bare area of liver, - Exophytic tumor, - Prior intervention like TACE/surgery)	Arranged from most common to least common: 1. Right and Left inferior phrenic artery 2. Omental branch: from gastroepiploic artery 3. Adrenal artery 4. Intercostal and subcostal artery: common levels of the intercostal arteries that supply HCCs are T9, T10, and T11. 5. Cystic artery: divided into superficial and deep branch. Superficial branch feds peritoneal surface of the gallbladder, and the deep branch (potential for tumor supply) supplies the gallbladder bed and portion of liver parenchyma . 6. Right and Left internal mammary artery: segment VIII and IV HCCs can have supply from the right internal mammary artery, and HCCs located in the left lateral segment can have supply from the left internal mammary artery 7. Renal or renal capsular artery 8. Branch of superior mesenteric artery 9. Right and Left gastric artery 10. Lumbar artery
Various Chemotherapy agents	1. Anthracycline: Doxorubicin, Epirubicin, Adriamycin, Pirarubicin 2. Raltitrexed: Raltitrexed 3. Pyrimidine: Fluorouracil Gemcitabine 4. Mitomycin: Mitomycin 5. Platinum: Cisplatin, Miriplatin, Lobaplatin 6. Ethanol: Ethanol
Most common single Chemotherapy regimen	Doxorubicin = 50-75 mg/m² body surface area, to a maximum of 150 mg Cisplatin = 50-100 mg/m² body surface area Epirubicin = 75 mg/m2 body surface area
Most common combination of chemotherapy agents used	1. Anthracycline + Mitomycin 2. Anthracycline + Mitomycin + Pyrimidine: Doxorubicin + Mitomycin + Gemcitabine) 3. Anthracycline + Mitomycin + Platinum: Epirubicin + Lobaplatin + Mitomycin 4. Anthracycline + Mitomycin: Doxorubicin + Mitomycin 5. Anthracycline + Platinum + Mitomycin + Pyrimidine: Epirubicin + Cisplatin + Mitomycin + Furuorouracil
TACE type	cTACE (conventional TACE), DEB-TACE (Drug Eluting Beads TACE)
Other Embolic Agents	Link
Super Selective TACE	Super-Selective TACE using a microcatheter and Cone-beam CT is recommended.
Response Evaluation	Tumor response to TACE can be assessed using objective radiologic response like mRECIST criteria for HCC, EASL etc
Re TACE regimen	Decision for Re TACE can be taken after patient assessment and using various scores like ART, ABCR, SNACOR. Atleast two TACE procedures performed 2-8 weeks apart are recommended prior to stopping due to lack of response.
Some Important Publication and studies	Link

Blood supply patterns of HCC and lipiodol dosage:

Type	CT & DSA Findings	Nourishing arteries	Notable Features	Lipiodol Dosing
Type I - Abundant Supply	Type Ia: Obvious homogeneous or non-homogeneous hyper-dense contrast in arterial phase and maintained enhancement through subsequent phases. Type Ib: Slight enhancement, relative hypodense in arterial and portal-venous phases.	Type Ia: Radiated, piebald, petal, or tuberous broadened vessels. Type Ib: Slightly broadened/nodular arteries; palisade shape enhancement in portal-venous phase.	Type Ia has more pronounced vessel features. Type Ib shows subtler enhancements.	1. Depends on blood supply of tumor, patient’s condition, tolerance, catheter position. More lipiodol needed for abundant supply. 2. Non- selective embolization: Over 5 mL for <5 cm tumors, up to 10 mL for >5 cm, higher for larger tumors. 3. Super-selective embolization: Over 20 mL for <10 cm tumors, up to 30 mL or more for >10 cm, higher for larger tumors.
Type II - Poor Supply	No or mild enhancement in all the phases.	No or slight widening of nourishing arteries; absence of small vessels.	Tumors show minimal response to contrast.	1. Lipiodol dose should be minimal, as excess can disperse into normal liver parenchyma. 2. Overdosing may lead to deterioration of hepatic function especially in cirrhotic patients.
Type III - Mixed Supply	Combination of sufficient and poor blood supply areas.	Areas with variable contrast enhancement.	Co-existence of well-supplied and poorly-supplied areas within a single tumor.	Depends on abundant blood supply area of tumor, patient’s condition, tolerance, catheter position.
Type IV - A-V Shunt	Early A-V shunt visible	Enlarged normal hepatic artery; A-V shunt evident.	Special attention needed due to A-V shunt dynamics.	Risk of pulmonary artery embolism in cases of hepatic arterial-venous fistula.

1. Lipiodol dose - 10 ml/m² body surface area
2. Lipiodol filling over 75% area of tumor is considered complete filling
3. Lipiodol filling 50%-70% area is considered comparatively complete filling

Contraindications:

Different Staging systems for HCC have slightly different exclusion criterias.

Factors	Absolute Contraindication
Liver Cirrhosis Related	1. Decompensated cirrhosis - Child-Pugh C, - Jaundice (T. Bilirubin > 2-3mg/dl), - Albumin < 3 g/dl, - Uncorrectable coagulopathy, - Poor patient performance status ECOG > 3, - Hepatic encephalopathy, - Refractory ascites, - Hepatorenal syndrome. 2. Impaired portal blood flow - Portal vein thrombus, - Hepatofugal blood flow
HCC Related	1. Extensive tumor involving the entirety of both lobes of liver 2. Malignant Portal Vein Thrombosis
Others	1. Untreatable arteriovenous Fistula 2. Acute Infection
Renal Related	1. S. Creatinine ≥ 2 mg/dl 2. Creatinine Clearance <30 ml/min

Factors	Relative Contraindication
Liver Cirrhosis Related	Untreatable esophageal varices with high risk of bleeding
HCC Related	Large Tumor > 10 cm
Others	1. Severe Comorbidities 2. Incompetent papilla with pneumobilia (owing to biliary stenting or surgery) 3. Biliary dilatation

Method of Preparation:

Prepare water-in-oil emulsion (aqueous chemotherapy droplets in internal phase and Lipiodol in continuous external phase) to improve tumor deposit.
The water-in-oil emulsion is obtained by mixing one volume of drug solution with two to three volumes of Lipiodol by pushing the drug syringe into the syringe containing Lipiodol.

Complications:

Post Embolization Syndrome (Most common) – Presents as pain, fever, nausea, and vomiting. Managed using analgesic, antipyretic, antiemetic, and antibiotics depending upon patient’s symptoms post TACE
Entry site complications (2-3%) – Hematoma, AV fistula, Pseudoaneurysm
Vascular Complications (Rare) – Arterial dissection, thrombosis, Vasospasm
Non-target embolization (Rare) – Chemical cholecystitis, Chemical pneumonitis
Others (Rare)– Biloma, Abscess

References