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## Complete Summary

#### GUIDELINE TITLE

Hepatic malignancy.

#### BIBLIOGRAPHIC SOURCE(S)

Brown DB, Bakal CW, Weintraub JL, Bass JC, Dickey KW, Gemery JM, Klyde
DP, Millward SF, Patel AA, Salem R, Selby JB Jr, Silberzweig JE, Expert
Panel on Interventional Radiology. Hepatic malignancy. \[online
publication\]. Reston (VA): American College of Radiology (ACR); 2007. 7
p. \[40 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Hepatic malignancy

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Gastroenterology\
Internal Medicine\
Oncology\
Radiology\
Surgery

#### INTENDED USERS

Health Plans\
Hospitals\
Managed Care Organizations\
Physicians\
Utilization Management

#### GUIDELINE OBJECTIVE(S)

To evaluate the appropriateness of interventional radiologic (ablative
and endovascular) procedures/treatments for hepatic malignancy

#### TARGET POPULATION

Patients with hepatic malignancies: hepatocellular carcinoma,
neuroendocrine tumors, colorectal metastases to the liver

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Transplantation

2.  Resection

3.  Thermal ablation

    -   Percutaneous

    -   Intraoperative

4.  Arterial chemoembolization

5.  Arterial radioembolization

6.  External beam radiation

7.  Systemic chemotherapy

8.  Arterial therapy combined with ablation

9.  Arterial embolization

10. Systemic chemotherapy

11. Chemical ablation

12. Long-acting octreotide

#### MAJOR OUTCOMES CONSIDERED

Utility of interventional radiologic (ablative and endovascular)
procedures/treatments for hepatic malignancy

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The guideline developer performed literature searches of peer-reviewed
medical journals and the major applicable articles were identified and
collected.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Not Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not stated

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

One or two topic leaders within a panel assume the responsibility of
developing an evidence table for each clinical condition, based on
analysis of the current literature. These tables serve as a basis for
developing a narrative specific to each clinical condition.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus (Delphi)

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Since data available from existing scientific studies are usually
insufficient for meta-analysis, broad-based consensus techniques are
needed for reaching agreement in the formulation of the appropriateness
criteria. The American College of Radiology (ACR) Appropriateness
Criteria panels use a modified Delphi technique to arrive at consensus.
Serial surveys are conducted by distributing questionnaires to
consolidate expert opinions within each panel. These questionnaires are
distributed to the participants along with the evidence table and
narrative as developed by the topic leader(s). Questionnaires are
completed by participants in their own professional setting without
influence of the other members. Voting is conducted using a scoring
system from 1-9, indicating the least to the most appropriate imaging
examination or therapeutic procedure. The survey results are collected,
tabulated in anonymous fashion, and redistributed after each round. A
maximum of three rounds is conducted and opinions are unified to the
highest degree possible. Eighty percent agreement is considered a
consensus. This modified Delphi technique enables individual, unbiased
expression, is economical, easy to understand, and relatively simple to
conduct.

If consensus cannot be reached by the Delphi technique, the panel is
convened and group consensus techniques are utilized. The strengths and
weaknesses of each test or procedure are discussed and consensus reached
whenever possible. If \"No consensus\" appears in the rating column,
reasons for this decision are added to the comment sections.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Criteria developed by the Expert Panels are reviewed by the American
College of Radiology (ACR) Committee on Appropriateness Criteria.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**ACR Appropriateness Criteria®**

**Summary of Recommendations**

-   Use of percutaneous ablative techniques vs. arterial methods will
    vary from institution to institution depending on operator
    expertise.

-   Thermal ablation or chemical ablation alone does poorly in treating
    tumors more than 3 cm in diameter. Combining thermal and arterial
    treatments may be better than arterial treatments alone, but this
    issue has not been formally studied.

-   Systemic chemotherapy is often temporarily effective for
    noncarcinoid islet cell tumors.

-   Resection may be indicated for dominant expansile tumors.

-   Radioembolization may be as effective as chemoembolization or
    embolization, but there is limited literature available to date.

**Variant 1: Hepatocellular carcinoma: Solitary tumor \<3 cm.**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Transplantation           9                    

  Resection                 8                    

  Percutaneous thermal      7                    
  ablation                                      

  Arterial                  6                    
  chemoembolization                             

  Intraoperative thermal    6                    
  ablation                                      

  Percutaneous chemical     5                    
  ablation                                      

  Arterial embolization     5                    

  Arterial                  5                    
  radioembolization                             

  External beam radiation   1                    

  Systemic chemotherapy     1                    

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Variant 2: Hepatocellular carcinoma: Solitary tumor 5 cm.**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Transplantation           9                    

  Resection                 8                    

  Arterial                  7                    
  chemoembolization                             

  Arterial therapy combined 7                    
  with ablation                                 

  Arterial embolization     6                    

  Arterial                  6                    
  radioembolization                             

  Thermal ablation          5                    

  Intraoperative thermal    4                    
  ablation                                      

  Systemic chemotherapy     3                   Especially in portal vein
                                                thrombosis.

  Chemical ablation         2                    

  External beam radiation   1                    

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Variant 3: Hepatocellular carcinoma: More than one tumor, at least one
of the tumors \>5 cm.**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Arterial                  8                    
  chemoembolization                             

  Arterial embolization     7                    

  Arterial                  7                    
  radioembolization                             

  Arterial therapy combined 6                   Depends on location of tumors.
  with ablation                                 

  Resection                 3                   Depends on location of tumors and
                                                status of liver.

  Intraoperative thermal    3                    
  ablation                                      

  Thermal ablation          3                    

  Transplantation           2                    

  Chemical ablation         2                    

  External beam radiation   1                    

  Systemic chemotherapy     No consensus        The expert panel recognizes this
                                                is a promising therapy. See text
                                                below.

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Variant 4: Metastatic liver disease: Multifocal metastatic
neuroendocrine tumor (includes carcinoid tumors as well as islet cell
tumors of the pancreas).**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Long-acting octreotide    9                    

  Arterial                  8                    
  chemoembolization                             

  Arterial embolization     8                    

  Arterial                  6                   Very limited published evidence.
  radioembolization                             

  Arterial therapy combined 4                    
  with thermal ablation                         

  Resection                 3                   Resection appropriate in limited
                                                number of patients.

  Intraoperative thermal    3                    
  ablation                                      

  Systemic chemotherapy     3                    

  Thermal ablation          3                    

  Transplantation           2                    

  External beam radiation   1                    

  Chemical ablation         1                    

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Variant 5: Metastatic liver disease: Multifocal colorectal carcinoma
(liver dominant or isolated), \>5 cm tumors.**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Systemic chemotherapy     9                    

  Resection                 7                   If resection is anatomically
                                                feasible.

  Arterial                  3                    
  chemoembolization                             

  Arterial embolization     3                    

  Arterial                  3                   Pending further data.
  radioembolization                             

  Intraoperative thermal    2                    
  ablation                                      

  Thermal ablation          2                    

  Transplantation           1                    

  External beam radiation   1                    

  Chemical ablation         1                    

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Variant 6: Solitary colorectal liver metastasis**

  -------------------------------------------------------------------------------
  **Treatment/Procedure**   **Appropriateness   **Comments**
                            Rating**            
  ------------------------- ------------------- ---------------------------------
  Resection                 9                    

  Systemic chemotherapy     9                   Appropriate alone and with
                                                resection.

  Thermal ablation          6                   If not a surgical candidate.

  Intraoperative thermal    4                    
  ablation                                      

  Arterial                  3                    
  chemoembolization                             

  Arterial embolization     3                    

  Arterial                  3                    
  radioembolization                             

  Chemical ablation         2                    

  Transplantation           1                    

  External beam radiation   1                    

  ***Appropriateness                            
  Criteria Scale*\                              
  1 2 3 4 5 6 7 8 9\                            
  1 = Least appropriate 9 =                     
  Most appropriate**                            
  -------------------------------------------------------------------------------

**Summary of Literature Review**

Management of hepatic malignancy remains a challenging problem. For
primary and many metastatic processes, traditional therapies such as
resection, systemic chemotherapy, or external beam radiation therapy are
unavailable or ineffective. A number of novel techniques have been
developed by interventional radiologists to treat patients with hepatic
malignancy. These treatment methods include direct tumor ablation via
chemical or thermal means and endovascular techniques such as
embolization, chemoembolization, and radioembolization with Yttrium-90
(Y90). The relative role of these treatments in management of various
disease processes is reviewed below.

**Hepatocellular Carcinoma**

Hepatocellular carcinoma (HCC) is the index tumor around which the
discipline of interventional oncology is based. The only cure for HCC is
liver transplantation. Unfortunately, the number of patients awaiting
transplant far outstrips the number of available organs. Patients
younger than 65 with limited tumor burden (described at many centers as
one tumor measuring 5 cm or less or up to three tumors all measuring
less than 3 cm) should undergo evaluation for transplantation. Patients
with adequate hepatic reserve may undergo resection if obtaining a
margin does not leave too small a remnant. Chemotherapy and external
beam radiation have traditionally been ineffective in treating these
tumors. Recently, results of a double-blinded randomized study of
Sorafenib versus placebo in patients with HCC, which is powered for
survival, have been reported. This trial demonstrated a statistically
significant improvement in survival of 10.7 versus 7.9 months in favor
of Sorafenib. The panel will await the publication of this data before
making a final recommendation. Since most patients are not candidates
for surgery, and in light of the ineffectiveness of other treatments,
newer therapies were developed in the 1980s and 1990s.

Ablative therapies are broken into two groups: chemical and thermal.
Chemical ablation is typically performed with absolute alcohol, while
thermal ablation most commonly refers to radiofrequency ablation (RFA)
or cryoablation. Ablative therapies are effective at treating small
HCCs. Ablative therapies can be performed either percutaneously or
surgically, using open or laparoscopic methods. Since most patients with
HCC are poor surgical candidates, this option may not be the most
appropriate. As tumor number and/or size (\>3 cm) increases, the
operator may want to focus on arterial-based therapies as a supplement.
A variety of endovascular techniques have been described to treat
hepatocellular carcinoma. These include chemoembolization, embolization,
and radioembolization.

Chemoembolization for HCC was initially controversial, as early
randomized trials did not demonstrate clinical benefit. However, these
trials had significant flaws in design. More recent trials have
demonstrated a significant survival benefit with use of
chemoembolization for HCC versus no treatment. One of these studies had
two separate treatment arms: chemoembolization and \"bland\"
embolization (i.e., treatment with particulate embolization alone). When
chemoembolization reached statistical significance versus no treatment,
the study was stopped. Bland embolization had not yet reached
statistical significance but outcomes in this group were much closer to
the chemoembolization group than to the no-treatment group.

Radioembolization with beta-emitting Y90 beads is emerging as another
treatment option for patients with HCC. Initial outcomes with this new
agent are similar to those described with chemoembolization and
embolization.

**Neuroendocrine Tumors**

Neuroendocrine tumors include carcinoid tumors which arise from the
small bowel, appendix, lung, bronchi, and pancreas, as well as
pancreatic islet cell malignancies with related hormonal symptoms from
glucagon, vasoactive intestinal peptide, insulin, and gastrin secretion.
Carcinoid tumors are much more common than islet cell tumors. Management
of these tumors is complex and varies depending on the aggressiveness of
the intrahepatic process and the presence or absence of related hormonal
syndromes.

For patients with hormonally active disease, most oncologists will
initially attempt to control symptoms with depot octreotide injections.
Resection of hepatic metastases can be performed in appropriate cases.
In carefully selected patients, 5-year survival rates can approach 70%,
although the symptom recurrence rate within 5 years is 84%.
Transplantation is uncommonly performed for neuroendocrine metastases.
Systemic chemotherapy has a limited role, with benefit more commonly for
islet cell than carcinoid tumors. Although thermal or chemical ablation
is feasible in certain cases, most patients present with multiple
bilobar metastases, making ablation a suboptimal option for the majority
of patients.

Many patients with neuroendocrine tumors present with bilateral hepatic
metastases and limited treatment options. Arterial therapies play a
significant role in management since these tumors receive most of their
supply from the hepatic arteries. Embolization and chemoembolization
have been shown to decrease hormonal symptoms and contribute to median
survival as long as 80 months. There has been preliminary research into
use of Y90 in this patient population, with ancecdotally promising
results.

**Colorectal Cancer Metastases to the Liver**

The gold standard in management of colon cancer metastatic to the liver
is resection. Unfortunately, most of these patients are not candidates
for surgery due to either disease bulk or the presence of extrahepatic
metastases. This group of patients should be treated with systemic
chemotherapy. A subgroup of patients with liver metastases will progress
after chemotherapy options are exhausted or toxicity from systemic
therapy limits chemotherapy options. These patients are potential
candidates for palliative ablative or arterial interventions.

Thermal ablation is accepted as preferable to chemical ablation for
treating colorectal metastases. As with HCC, ablation should be reserved
for patients with a limited number of smaller tumors. Local recurrence
is significantly higher when colorectal metastases larger than 2.5 cm
are treated and when more than one tumor is present at the time of
ablation. Larger tumors may be treated with a combination of ablation
and arterial embolization or chemoembolization.

Arterial therapies such as chemoembolization have been studied with
limited results. Patients without extrahepatic disease survive longer
than those with extrahepatic disease following chemoembolization. Use of
Y90 for liver-dominant colorectal metastases is expanding, with early
response rates reported to be as high as 79%. Determination of the
effect of Y90 on survival rates is evolving.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are based on analysis of the current literature and
expert panel consensus.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Selection of appropriate interventional radiologic (ablative and
endovascular) procedures/treatments for hepatic malignancy

#### POTENTIAL HARMS

Not stated

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

An American College of Radiology (ACR) Committee on Appropriateness
Criteria and its expert panels have developed criteria for determining
appropriate imaging examinations for diagnosis and treatment of
specified medical condition(s). These criteria are intended to guide
radiologists, radiation oncologists, and referring physicians in making
decisions regarding radiologic imaging and treatment. Generally, the
complexity and severity of a patient\'s clinical condition should
dictate the selection of appropriate imaging procedures or treatments.
Only those exams generally used for evaluation of the patient\'s
condition are ranked. Other imaging studies necessary to evaluate other
co-existent diseases or other medical consequences of this condition are
not considered in this document. The availability of equipment or
personnel may influence the selection of appropriate imaging procedures
or treatments. Imaging techniques classified as investigational by the
U.S. Food and Drug Administration (FDA) have not been considered in
developing these criteria; however, study of new equipment and
applications should be encouraged. The ultimate decision regarding the
appropriateness of any specific radiologic examination or treatment must
be made by the referring physician and radiologist in light of all the
circumstances presented in an individual examination.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Personal Digital Assistant (PDA) Downloads

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Brown DB, Bakal CW, Weintraub JL, Bass JC, Dickey KW, Gemery JM, Klyde
DP, Millward SF, Patel AA, Salem R, Selby JB Jr, Silberzweig JE, Expert
Panel on Interventional Radiology. Hepatic malignancy. \[online
publication\]. Reston (VA): American College of Radiology (ACR); 2007. 7
p. \[40 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2007 Jan

#### GUIDELINE DEVELOPER(S)

American College of Radiology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

The American College of Radiology (ACR) provided the funding and the
resources for these ACR Appropriateness Criteria®.

#### GUIDELINE COMMITTEE

Committee on Appropriateness Criteria, Expert Panel on Interventional
Radiology

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Panel Members*: Daniel B. Brown, MD; Curtis W. Bakal, MD; Joshua L.
Weintraub, MD; James C. Bass, MD; Kevin W. Dickey, MD; John M. Gemery,
MD; David P. Klyde, MD; Steven F. Millward, MD; Aalpen A. Patel, MD;
Riad Salem, MD; John B. Selby, Jr., MD; James E. Silberzweig, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[American College of Radiology (ACR) Web
site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonInterventionalRadiology/HepaticMalignancy.aspx).

ACR Appropriateness Criteria® *Anytime*, *Anywhere*™ (PDA application).
Available from the [ACR Web
site](http://www.acr.org/SecondaryMainMenuCategories/ACRStore/FeaturedCategories/QualityandSafety/ac_pda.aspx).

Print copies: Available from the American College of Radiology, 1891
Preston White Drive, Reston, VA 20191. Telephone: (703) 648-8900.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   ACR Appropriateness Criteria®. Background and development. Reston
    (VA): American College of Radiology; 2 p. Electronic copies:
    Available in Portable Document Format (PDF) from the [American
    College of Radiology (ACR) Web
    site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI Institute on November 13, 2007.

#### COPYRIGHT STATEMENT

Instructions for downloading, use, and reproduction of the American
College of Radiology (ACR) Appropriateness Criteria® may be found on the
[ACR Web
site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/ACRAppropriatenessCriteriaTermsandConditionsDoc1.aspx).

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008