Hepatic Chemoembolization

Anatomy and Physiology

The liver embryologically develops into lobes and segments. Several classification schemes describe these segments, but the most widely used is the Couinaud classification. In this classification, the segments are defined by the combination of the following components:

• Systemic (hepatic) draining vein
• The third order (third branch) portal vein supplying these segments with blood from the intestines and spleen

The arterial liver supply is variable. The most common configuration is that of a single proper hepatic artery derived from a common hepatic artery derived from the celiac artery. The proper hepatic artery divides into right and left branches to feed the right and left lobes of the liver, respectively. However, this configuration is probably present in less than 50% of individuals; various sources give various percentages. Authors disagree on the correct name for the artery that supplies segment 4, which is termed the middle hepatic artery by some and a segment 4 branch by others.[3] The caudate lobe has a particularly variable supply, often with multiple branches from the right and left hepatic arteries.

The following are the 3 most common potential sources of accessory arterial supply to liver tumors:

• The right phrenic artery (sometimes called the inferior phrenic artery)
• A replaced or accessory left hepatic artery
• The right internal mammary artery (ie, the internal thoracic artery)

The following 4 arteries should be kept in mind as common avenues for inadvertent (unintended spread of) chemoembolization, which results in injury to nontarget healthy tissues:

• Cystic artery
• Right gastric artery
• Falciform artery
• Duodenal (or supraduodenal) artery

Indications

The most widely used guidelines for cancer management in the United States are those created by the National Comprehensive Cancer Network (NCCN). The NCCN is a nonprofit organization composed of selected hospitals, mostly university hospitals, that choose member physicians from multiple specialties to sit on panels; these panels have made national guidelines for cancer treatment since 1995.

According to the NCCN's review of medical research, transarterial chemoembolization (TACE) is a therapeutic option for hepatocellular carcinoma and liver metastases. However, TACE is not a first option for any liver cancer because TACE itself does not cure liver cancer of any kind. Thus, TACE should only be selected after a process of elimination of surgery and ablation, either of which has the potential to cure liver cancer. In a minority of situations, TACE can change a patient's status from "incurable" to "curable" by downsizing 1 or more hepatic tumors, subsequently qualifying the patient for surgery (Please refer to the Clinical Significance section for more information).

Thus, patients with the following characteristics are appropriate candidates for TACE:

• Individuals with such an advanced tumor status or overall poor health that they are not able to withstand surgery or to gain a survival benefit from it as a first-line option are candidates.

AND

• Patients must also be healthy enough to withstand the potential adverse events and toxicity of TACE and have good enough odds of gaining at least several months of additional survival at a reasonable quality of life.

Hepatic Tumor Treatment Algorithms

The NCCN updates its flow chart algorithm multiple times a year to discern which treatment is the best first-line treatment, and the discussion in this activity is based on the most updated algorithm. The NCCN usually relies on the American Joint Committee on Cancer (AJCC) staging system to create algorithms for treating various cancers based on cancer staging. However, the AJCC staging system does not consider liver function, which is critical in determining prognosis and potential survival benefit. When considering treatment options for HCC and metastatic disease to the liver, the NCCN requires scoring how the liver is functioning and affecting other organs using the following scoring systems:

• The Child-Pugh-Turcotte score is often referred to only as the Child-Pugh score; this score is calculated from the serum creatinine, serum total bilirubin, international normalised ratio (INR), and presence or absence of encephalopathy and ascites. 
• The United Network for Organ Sharing (UNOS) score is commonly called the Model for End-stage Liver Disease (MELD) score instead. The UNOS/MELD score is also based on the patient's creatinine, total bilirubin, and INR; it replaces the other 2 components with how the liver affects renal function through the hepatorenal syndrome, which are serum sodium and the presence or absence of the need for dialysis at least twice weekly. A modification of this score, called the MELDNa score, includes the serum sodium. UNOS currently uses this score for organ allocation decision making, but studies performed to assess TACE safety do not use the MELDNa score. 

Additionally, the decision regarding first-line therapy relies on scoring the tumor burden using criteria established based on a study of 48 patients at the University of Milan.[4] Use of the Milan criteria has shown that liver transplant is a preferred hepatocellular carcinoma (HCC) treatment in the following settings:

• The liver contains no more than 1 tumor exceeding 5 cm in maximum span
• No more than 3 tumors are present, with each tumor not exceeding 3 cm in maximum span

The NCCN does not use alternative tumor burden criteria, such as those from the University of California at San Francisco.

Multiple other HCC staging systems have been proposed because not all HCCs are identical. For example, HCC behavior depends in part on the following:

• Whether HCC developed secondary to hepatitis C, hepatitis B, alcohol-induced, or another cause
• Molecular marker expression

Results from research studies comparing populations with these different HCC factors found moderately different survival estimates. Available staging systems related to these different populations include, but are not limited to, the following:

• Okuda, 1985, Japan [5]
• Cancer of the Liver Italian Program, 1998, Italy [6]
• Barcelona Clinic Liver Cancer, 1999, Spain [7]
• Chinese University Prognostic Index, 2002, China [8]
• Japan Integrated Staging, 2003, Japan [9]
• American Joint Committee on Cancer, 2017, United States

Kinoshita reviews these and other staging systems' differences, strengths, and weaknesses.[10] An overlap between these systems is present. The NCCN previously did not favor one but now favors the Barcelona Clinic Liver Cancer (BCLC) staging system, which is also endorsed by the American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver Disease (EASLD). The BCLC is a conglomeration of other staging systems, including the Child-Pugh score and the Eastern Cooperative Oncology Group (ECOG) performance status score. In the BCLC, patients are divided into stages 0, A, B, C, and D from least to most severe condition. BCLC stage B patients are an extremely heterogeneous group, ranging from having 4 subcentimeter tumors to having a liver replaced entirely with tumor. 

The following is a breakdown of patient factors that determine how TACE may be used based on the NCCN guidelines. All candidates for TACE have the following characteristics:

• Not a candidate for hepatectomy/transplant/ablation alone due to tumor burden or overall ECOG performance status
• Child-Pugh class A or B (not C)
• ECOG performance status score <3

Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma

In patients where TACE intends to keep the patient a candidate for resection/transplant (ie, "bridging" therapy), the following are present:

• No vascular invasion on imaging
• No extrahepatic spread on imaging
• Tumors meet the Milan criteria
• Suitable healthy liver remnant/adequate healthy liver reserve
• Patient meets other criteria for transplant (eg, ECOG performance status score of 0 or 1 and no portal hypertension)

In patients where TACE intends to downstage the tumors so that the patient qualifies for a transplant (usually a tumor of 3 to 5 cm), the following are present:

• The presence of the above factors, but the tumor burden is just outside of the Milan criteria
• Tumors between 3 and 5 cm may undergo TACE in combination with microwave ablation

In patients where TACE intends to palliate only (usually a tumor of >5 cm), the following factors are present: 

• At least 1 lesion does not qualify for resection, regardless of the outcome of TACE
• The patient does not qualify for a transplant
• The clinicians involved recommend against radiation therapy or systemic therapy

Patient With Liver Metastasis

In patients where TACE intends to downstage to keep the patient a candidate for curative resection/ablation, the following factors are present:

• All liver and primary lesions are considered potentially curable by ablation or by resection
• The patient is willing to be treated as part of a clinical trial
• Initial chemotherapy failure may or may not have occurred

In patients for whom TACE is intended to palliate, the following factors are present:

• At least 1 lesion does not qualify for resection, regardless of the outcome of TACE
• Initial chemotherapy has failed
• The hepatic tumor burden is predominant or is the primary cause of symptoms

In all these situations, the patient should understand that TACE may be unsuccessful and not significantly extend or improve the quality of life. Moreover, in patients with liver metastasis, TACE can be considered a second-line treatment after first-line treatment has failed, usually as part of a clinical trial. No guidelines from the NCCN or clinical trials that calculate expected survival benefits when TACE is used as a second-line therapy have been established. 

Contraindications

Absolute Contraindications

The NCCN omits TACE in its treatment algorithm for primary liver tumors other than HCC (eg, cholangiocarcinoma). However, an absolute contraindication to TACE is when a superior treatment option exists. In general, surgery (either transplant or partial hepatic resection) is the most effective treatment for curing primary or metastatic liver cancer. Ablation is considered the first-line treatment over arterially directed therapy when the criteria for ablation are met.

However, many patients will not qualify for surgery or ablation due either to properties of the tumors or their overall health status that have been shown by research to make either of these options no more effective and potentially more dangerous than TACE. All tumors considered for surgery or ablation should be "amenable to complete treatment" (eg, should be <3 cm with a margin of normal liver tissue around the tumor in an accessible location for a percutaneous, laparoscopic, or open approach) according to the NCCN.

Other absolute contraindications to hepatic chemoembolization include:

• No expected benefit in survival or quality of life
  • However, this can be predicted if the patient has an ECOG performance status score of >2, ie, someone who is completely disabled, cannot self-care, or who is confined to a bed or chair for reasons other than a purely musculoskeletal injury.
• Contraindications to chemotherapy (eg, heart or kidney failure and leukopenia)
• Patients are unwilling or unable to comply with follow-up guidelines
• Child-Pugh class C (according to the NCCN)

Relative Contraindications

Relative contraindications to TACE include, but are not limited to, the following:

• Excessive tumor burden (eg, metastases, malignant ascites, largest tumor >5 cm)
• Hypovascular tumor based on appearance on magnetic resonance imaging or computed tomography
• Main portal vein thrombosis (eg, is associated with a high risk of posttreatment liver failure)
• Biliary obstruction or bilirubin >3 mg/dL, unless segmental injections can be performed
• Any features of decompensated/end-stage cirrhosis or poor Child-Pugh or MELD scores (decompensated cirrhosis is defined as the presence of ascites, encephalopathy, jaundice, or variceal bleeding)
• Active alcohol consumer

In general, no more than 50% of liver volume should be chemoembolized at a time. Therefore, if a patient has a tumor occupying more than 50% of the liver volume, that patient is best treated with serial TACE procedures. Portal vein thrombosis or invasion is not a contraindication to palliative TACE if there is adequate collateral hepatopetal flow to supply the liver parenchyma to be embolized. Portal vein invasion necessitates selective or segmental embolization, a good performance status, or nonlobar embolization to avoid too much hepatic necrosis and liver failure. Many clinicians treat bile duct obstruction before offering TACE, which could exacerbate the obstruction.

Equipment

TACE can be divided into the following 2 major categories of chemotherapy delivery:

1. TACE with drug-eluting embolization particles
2. TACE in which the active chemotherapy drug and the embolization particles are separate agents (ie, conventional)

Conventional TACE (cTACE) is a mixture of the following 3 agents:

• Lipiodol contrast agent
• A chemotherapy drug
• An embolization agent not chemically bound to the chemotherapy drug

TACE using drug-eluting beads (TACE-DEB or DEB-TACE) uses resin beads bound to the chemotherapy agent itself that slowly release the chemotherapy over time. Currently, only 2 chemotherapy drugs are United States Food and Drug Administration-approved for use in this manner. Doxorubicin is used to treat hypervascular primary hepatic tumors and metastases; irinotecan is used to treat metastases from colorectal cancer.

Preparation

Imaging Studies

Imaging to evaluate the arterial anatomy of the liver is "necessary" before TACE according to the NCCN guidelines. Some institutions perform a conventional arteriogram, whereas many use contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). Such imaging helps determine whether anatomy or pathology  findings  are noted that may prevent TACE from being safe or effective, including:

• The main portal vein is thrombosed.
• A high risk of embolic particles refluxing into areas of healthy tissue (non-target embolization) is present.
• Accessory arteries supply the tumor.
• The liver has an arterial supply of atypical size or embryologic origin.

Biopsy Evaluation

No biopsy is necessary if any of the following are noted:

• A tumor meets the criteria for HCC based on its enhancement pattern on multiphase CT or MRI in a patient with risk factors for developing HCC.
• Clear evidence of an extrahepatic primary tumor on imaging is noted, along with tumors in the liver that have behaved on contrast-enhanced imaging as expected for metastases. 

The NCCN suggests biopsy consideration before treatment in the following presentations:

• A liver lesion is suspected of malignancy but does not meet imaging criteria for HCC (eg, defined by the American College of Radiology Liver Reporting and Data System).
• A liver lesion meets imaging criteria for HCC, but the patient has any of the following:
  • Is not considered to have any risk factors for HCC, eg, cirrhosis or chronic hepatitis
  • Has risk factors for cholangiocarcinoma instead of HCC, eg, elevated serum CA 19-9 or carcinoembryonic antigen level
  • Is part of a research trial in which histologic grading or molecular characterization is needed

Anesthesia

TACE is typically performed using conscious sedation. Determination of periprocedural anesthesia risk is site-dependent. Many hospitals require physicians to assess the patient using the American Society of Anesthesiology (ASA) physical classification system and a Mallampati score. If the patient is ASA class 4 or higher or has any other anesthetic risk factors, eg, a high-risk airway, then some institutions and authors recommend that the patient should undergo consultation with an anesthesiologist or medical specialist (eg, a cardiologist) to address the pertinent risk factors.

Hydration

Many radiologists administer normal intravenous saline intravenously for hydration.

Infection Prevention

Because chemoembolization creates a bed of necrotic tissue, and such tissue may form an abscess, nearly all radiologists prescribe prophylactic antibiotics during the procedure. Regimens should cover gram-positive cocci, gram-negative rods, and in the case of patients without an intact sphincter of Oddi from previous surgery, sphincterotomy or biliary drainage, anaerobes. Recommended antibiotic regimens and the incidence of abscess infection are addressed by the Society of Interventional Radiology (SIR) guidelines.[11][12][13][14][15][16][17] If a bilioenteric anastomosis or biliary stent is present, some radiologists prescribe a bowel cleansing preparation, such as oral neomycin-erythromycin.

Bleeding Prevention

The SIR 2013 guidelines specify parameters for preventing bleeding complications (lab tests and medication withdrawal).[18]

Other Symptom Control

In patients being treated for carcinoid tumors, pre- or intraprocedure administration of octreotide may prevent or diminish the adverse events from serotonin release (ie, "carcinoid crisis"). Other preprocedure medications may include antiemetics and steroids. However, some radiologists only administer this postprocedure either routinely or as needed.

Technique or Treatment

The maximum chemotherapy administered (eg, 75 mg doxorubicin) is precalculated based on whether a tumor is present in one lobe or both lobes of the liver. TACE via the left transradial access, with patients in the feet-first position, reduced the radiation dose received by the operator.[19]

Basic steps of the procedure include:

• Arterial catheter access is obtained at an entry point (usually the femoral or radial artery) that the operator feels will enable the highest chance of procedure success.
• Arteriography is performed to document the arterial supply to single or multiple tumors.
• Arteries with a high risk of enabling nontarget embolization are occluded, usually with coils.
• A catheter with an outer diameter of about 1 mm, called a microcatheter, is usually needed to reach inside the liver to the artery or arteries feeding the tumor.
• The catheter or microcatheter is placed as close to the location as possible, which is thought to result in successful embolization of the artery or arteries feeding the tumor.
• The embolization particles, contrast, and chemotherapy are administered until stasis of arterial flow is seen during fluoroscopy.
• Follow-up arteriography documents the persistence or absence of flow to the region of interest.

Complications

Significant complications occur in approximately 5 to 10 out of 100 people who undergo TACE.[20] The most common major complications include:

• Liver failure
• Death from any cause
• Abscess

Besides these complications, other major complications have included:

• Tumor rupture
• Cholecystitis
• Biloma
• Permanent biliary stricture
• Arterial dissection
• Pulmonary emboli
• Tissue injury from nontarget embolization, with sequelae (eg, gastrointestinal hemorrhage) [21][22][23]

Clinical Significance

The SIR defined technical success as expected catheter placement and administration of the selected particles and drug, which should occur at a rate of at least 98%.[20] Another definition of technical success is initial tumor response, meaning tumor shrinkage. Clinical success is usually defined as downstaging or lengthened overall survival (OS), where OS means increased length of life in people treated with TACE compared to people with similar features who did not undergo TACE. No national organization has set a recommended threshold for this parameter. A less common definition is the length of tumor progression-free survival. The success rates of TACE for HCC are described below, focusing on results from randomized controlled trials (RCTs). Beyond this article's scope are success rates for TACE for metastatic disease and success rates for other treatments for HCC approved by the NCCN, including: 

• Intravenous chemotherapy
• External beam radiation
• Tumor ablation with heat (microwaves or radio waves) or cold (cryoablation) via percutaneous or open surgical approaches

Transarterial Chemoembolization for Lengthening Hepatocellular Carcinoma Survival

In 2002, 2 randomized trials with fewer than 100 patients in each treatment arm showed improved OS after TACE versus no treatment.[24][25] Based on the mortality rate after 1 year, the studies showed that TACE reduced the absolute risk of death by 19% to 26%, meaning that the number needed to treat with TACE to prevent 1 death was at least 4 to 5 people. However, in each study, selected patients underwent repeat TACE sessions. Therefore, the number needed to treat to prevent 1 death after 1 year is higher. 

A third prospective and controlled but nonrandomized study also found a survival benefit, as did a meta-analysis of 5 prospective studies.[26] Nevertheless, because TACE rarely completely eradicates HCC, TACE remains considered a noncurative therapy. A meta-analysis in 2003 led by an author of 1 of the RCTs mentioned above found evidence that TACE typically extended life by only 3 to 4 months for patients having BCLC stage B disease and HCC.[24]

Transarterial Chemoembolization for Downstaging Hepatocellular Carcinoma

An expected rate of downstaging is unknown. Yao, in a retrospective case series, reported that downsizing was accomplished by the “best minimally invasive method” (for example, RFA, TACE, PEI, or some combination) in 21 of 30 patients that met the following criteria:

• A lesion measuring 5 to 8 cm
• Between 2 and 3 lesions, at least 1 lesion 3 cm to 5 cm, and total tumor diameter <8 cm
• Between 4 and 5 lesions, all <3 cm, and total tumor diameter <8 cm [27]

However, results from other RCTs and other studies have reported rates of downsizing anywhere from 50% to 0%.[28][29] 

Transarterial Chemoembolization for Metastatic Disease To The Liver Lengthened Survival

The expected survival benefit for patients with tumors metastatic to the liver is even more variable than it is for patients with HCC, and results generally are not as encouraging as for patients with HCC. TACE is typically used for palliation only following systemic chemotherapy. The NCCN highlights DEB-TACE for this indication but does not state or conclude that a certain arterial-directed therapy (ATD) is better than another and instead cites a meta-analysis that concluded no ATD is superior for this indication.[30] The NCCN does not recommend TACE for treating any organs containing metastases besides the liver.

Transarterial Chemoembolization Compared with Ablation

Ablation is considered a superior treatment over ATDs when criteria for ablation are met because, unlike ATDs, for some tumors (eg, small HCCs), ablation can reach near equivalent cure rates as resection or transplantation.[31][32][33] Results from 2 RCTs showed that improved OS with combined TACE and ablation for liver tumors is observed only in tumors measuring 3 to 5 cm.[34][35] Results from an RCT with HCC of 3 to 5 cm demonstrated that patients treated with the combination of conventional TACE and ablation resulted in improved intratumoral response (ITR) and OS at 3 years compared to TACE or ablation alone.[36] 

Transarterial Chemoembolization Compared with Other Arterially Directed Therapies

The NCCN has yet to favor one ATD over another. Compared to TAE, one RCT with cTACE showed no statistically significant differences in ITR, progression-free survival, or OS.[37] Compared to cTACE, DEB-TACE has been associated with improved tolerability (less pain) and reduction in liver toxicity in some but not all RCTs, but it has not been shown to increase ITR or OS.[38][39][40] Compared to TARE, based on the results of 2 RCTs, TARE resulted in a longer TTP and less liver toxicity and pain. TACE often involves a 1-day hospital stay, while TARE often does not.[29][41] Whether and when TARE increases OS is still uncertain.

Transarterial Chemoembolization Compared with Chemotherapy and Radiation

The NCCN recommends TACE over chemotherapy when the possibility of transplant or resection is present. However, the NCCN does not identify a preferred approach when comparing TACE or external radiation due to a lack of evidence demonstrating either being more effective. For palliative intent only, the NCCN does not distinguish TACE as recommended before or after chemotherapy or external radiation, even though some RCTs' results have shown evidence of superior performance of either chemotherapy or external radiation over TACE.[42] Treatment with various chemotherapies and TACE combined can result in an improved OS over either alone.[43][44][45]

Enhancing Healthcare Team Outcomes

Effective delivery of hepatic chemoembolization requires a highly coordinated interprofessional team approach to ensure optimal patient-centered care, safety, and outcomes. Clinicians, including interventional radiologists, medical, surgical, and radiation oncologists, transplant surgeons, and nurses, must collaboratively evaluate the patient’s clinical profile and cancer stage to determine the appropriateness of hepatic chemoembolization. Strategic decision-making includes assessing tumor burden, liver function, and the potential for curative or palliative outcomes. Pharmacists play a crucial role in preparing chemotherapeutic agents and monitoring drug interactions or toxicity, while nurses provide essential peri-procedural support, education, and monitoring for complications. Hepatologists and primary care clinicians help manage underlying liver disease and comorbidities, supporting treatment readiness and recovery.

Interprofessional communication and care coordination are vital in reducing postprocedure complications and enhancing patient outcomes. Timely and clear communication among all healthcare professionals ensures seamless transitions across care settings and promotes consistency in follow-up plans. A designated healthcare professional, often a nurse navigator or advanced clinician, should serve as the central point of contact for the patient, helping to interpret treatment recommendations, schedule follow-up care, and respond to emerging concerns. This centralized role improves team performance, minimizes delays in care, and fosters trust, empowering patients to actively participate in their treatment journey.