Radioembolization for Primary and Metastatic Tumors of the Liver

POLICY NUMBER

A.8.01.43

DESCRIPTION

Radioembolization (RE), also referred to as selective internal radiotherapy, delivers small beads (microspheres) impregnated with yttrium 90 intra-arterially via the hepatic artery. The microspheres, which become permanently embedded, are delivered to tumors preferentially because the hepatic circulation is uniquely organized, whereby tumors greater than 0.5 cm rely on the hepatic artery for blood supply while the normal liver is primarily perfused via the portal vein.Radioembolization has been proposed as a therapy for multiple types of primary and metastatic liver tumors.

Treatments for Hepatic and Neuroendocrine Tumors

The use of external-beam radiotherapy and the application of more advanced radiotherapy approaches (eg, intensity-modulated radiotherapy) may be of limited use in patients with multiple diffuse lesions due to the low tolerance of the normal liver to radiation compared with the higher doses of radiation needed to kill the tumor.

Various nonsurgical ablative techniques have been investigated that seek to cure or palliate unresectable hepatic tumors by improving locoregional control. These techniques rely on extreme temperature changes (cryosurgery or radiofrequency ablation), particle and wave physics (microwave or laser ablation), or arterial embolization therapy including chemoembolization, bland embolization, or radioembolization.

RadioembolizationRadioembolization (referred to as selective internal radiotherapy in older literature) delivers small beads (microspheres) impregnated with yttrium-90 intra-arterially via the hepatic artery. The microspheres, which become permanently embedded, are delivered to tumors preferentially because the hepatic circulation is uniquely organized, whereby tumors greater than 0.5 cm rely on the hepatic artery for blood supply while the normal liver is primarily perfused via the portal vein. Yttrium-90 is a pure beta-emitter with a relatively limited effective range and a short half-life that helps focus the radiation and minimize its spread. Candidates for radioembolization are initially examined by hepatic angiogram to identify and map the hepatic arterial system. At that time, a mixture of technetium 99-labeled albumin particles are delivered via the hepatic artery to simulate microspheres. Single-photon emission computed tomography imaging is used to detect possible shunting of the albumin particles into gastrointestinal or pulmonary vasculature.

Currently, two commercial forms of yttrium-90 microspheres are available: a glass sphere (TheraSphere) and a resin sphere (SIR-Spheres). Noncommercial forms are mostly used outside the United States. While the commercial products use the same radioisotope (yttrium 90) and have the same target dose (100 gray), they differ in microsphere size profile, base material (i.e., resin vs glass), and size of commercially available doses. The physical characteristics of the active and inactive ingredients affect the flow of microspheres during injection, their retention at the tumor site, spread outside the therapeutic target region, and dosimetry calculations. The U.S. Food and Drug Administration (FDA) granted premarket approval of SIR-Spheres for use in combination with 5-floxuridine chemotherapy by hepatic arterial infusion to treat unresectable hepatic metastases from colorectal cancer. In contrast, TheraSphere's glass sphere was approved under a humanitarian device exemption for use as monotherapy to treat unresectable hepatocellular carcinoma. In 2007, this humanitarian device exemption was expanded to include patients with hepatocellular carcinoma who have partial or branch portal vein thrombosis. For these reasons, results obtained with a product do not necessarily apply to another commercial (or non-commercial) product.

Currently, two forms of yttrium-90 microspheres have been approved by the FDA.

In 1999, TheraSphere® (Boston Scientific; previously manufactured by Nordion, under license by BTG International), a glass sphere system, was approved by the FDA through the humanitarian drug exemption process for radiotherapy or as a neoadjuvant treatment to surgery or transplantation in patients with unresectable hepatocellular carcinoma who can have placement of appropriately positioned hepatic arterial catheters (H980006).

On March 17, 2021, TheraSphere received approval through the premarket approval process for use as selective internal radiation therapy (SIRT) for local tumor control of solitary tumors (1 to 8 cm in diameter), in patients with unresectable hepatocellular carcinoma, Child-Pugh Score A cirrhosis, well-compensated liver function, no macrovascular invasion, and good performance status (P200029).

In 2002, SIR-Spheres® (Sirtex Medical), a resin sphere system, was approved by the FDA through the premarket approval process for the treatment of inoperable colorectal cancer metastatic to the liver (P990065).

POLICY

Radioembolization may be considered medically necessary to treat primary hepatocellular carcinoma that is unresectable and limited to the liver(See Policy Guidelines).

Radioembolization may be considered medically necessary in primary hepatocellular carcinoma as a bridge to liver transplantation.

Radioembolization may be considered medically necessary to treat primary intrahepatic cholangiocarcinoma in individuals with unresectable tumors.

Radioembolization may be considered medically necessary to treat hepatic metastases from neuroendocrine tumors (carcinoid and noncarcinoid) with diffuse and symptomatic disease when systemic therapy has failed to control symptoms.

Radioembolization may be considered medically necessary to treat unresectable hepatic metastases from colorectal carcinoma, melanoma (ocular or cutaneous), or breast cancer that are both progressive and diffuse, in individuals with liver-dominant disease who are refractory to chemotherapy or are not candidates for chemotherapyor other systemic therapies.

Radioembolization is considered investigational for all other hepatic metastases except as noted above.

Radioembolization is considered investigational for all other indications not described above.

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity. 

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

In general, radioembolization is used for unresectable hepatocellular carcinoma that is greater than 3 cm.

There is little information on the safety or efficacy of repeated radioembolization treatments or on the number of treatments that should be administered.

Radioembolization should be reserved for individuals with adequate functional status (Eastern Cooperative Oncology Group Performance Status 0 to 2), adequate liver function and reserve, Child-Pugh class A or B, and liver-dominant metastases.

Symptomatic disease from metastatic neuroendocrine tumors refers to symptoms related to excess hormone production.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

3/25/2004: Approved by Medical Policy Advisory Committee (MPAC).

4/29/2004: Code Reference section completed.

7/10/2009: Policy reviewed, no changes.

09/03/2010: Changed "Selective Internal Radiation Therapy" to "Radioembolization" in the title and throughout policy. Policy statement re-written to indicate that selective cases of hepatocellular carcinoma and metastatic neuroendocrine tumors may be considered medically necessary. Code Reference section changed from non-covered to covered. Added ICD-9 codes 155.0-155.2, 197.7, and 209.72 as covered diagnoses.

06/21/2011: Deleted the following policy statement: Radioembolization is considered investigational to treat unresectable hepatic metastases from colorectal carcinoma. Added a policy statement to indicate that radioembolization may be considered medically necessary to treat unresectable hepatic metastases from colorectal carcinoma that are both progressive and diffuse in patients with liver-dominant disease who are refractory to chemotherapy or are not candidates for chemotherapy.

04/26/2012: Policy reviewed; no changes.

08/09/2013: Added policy statement to indicate that radioembolization is considered investigational to treat primary intrahepatic cholangiocarcinoma.

04/29/2014: Policy reviewed; description updated. Added information regarding unresectable intrahepatic cholangiocarcinoma to the policy description. Added a policy statement to indicate that radioembolization is consideredinvestigational for all other indications not described.

09/01/2015: Code Reference section updated for ICD-10. Added ICD-9 procedure codes 38.86 and 99.29. Removed deleted CPT codes 37204 and 75894 and replaced with 37243.

11/13/2015: Policy description updated regarding yttrium-90 microspheres. Medically necessary policy statement updated to state that radioembolization may be considered medically necessary to treat unresectable hepatic metastases from colorectal carcinoma, melanoma (ocular or cutaneous),or breast cancer that are both progressive and diffuse, in patients with liver-dominant disease who are refractory to chemotherapy or are not candidates for chemotherapy or other systemic therapies. Investigational policy statement revised tostate that radioembolization may be considered medically necessary to treat primary intrahepatic cholangiocarcinoma in patients with unresectable tumors. It previously stated: Radioembolization is considered investigational to treat primary intrahepatic cholangiocarcinoma.Policy guidelines updated regarding radioembolization and to add medically necessary and investigative definitions.

12/08/2015: Code Reference section updated to add ICD-10 diagnosis code C22.1.

05/26/2016: Policy number A.8.01.43 added.

09/22/2016: Policy description updated. Policy statements unchanged.

08/11/2017: Policy description updated. Policy statements unchanged.

08/13/2018: Policy description updated. Policy statements unchanged.

08/16/2019: Policy reviewed; no changes.

08/19/2020: Policy reviewed; no changes.

12/06/2021: Policy description updated regarding devices. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

08/24/2022: Policy reviewed. Policy statements unchanged. Policy description updated to change "Child-Pugh score" to "Child-Pugh class."

08/14/2023: Policy reviewed. Policy statements and Policy Guidelines updated to change "patients" to "individuals."

08/16/2024: Policy reviewed; no changes.

09/15/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.01.43

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document. 

Covered Codes

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