Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Radioembolization for Primary and Metastatic Tumors of the Liver (Independence Administrators)

Policy #:09.00.48f

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

MEDICALLY NECESSARY

Coverage is subject to the terms, conditions, and limitations of the member's contract.

Radioembolization (i.e., TheraSphere®, SIR-Spheres®) is considered medically necessary and, therefore, covered when used for any of the following indications:
  • To treat primary hepatocellular carcinoma that is unresectable and limited to the liver.
  • As a palliative treatment for unresectable cholangiocarcinoma.
  • To treat primary hepatocellular carcinoma when used as a bridge to liver transplantation.
  • To treat hepatic metastases from neuroendocrine tumors (carcinoid and noncarcinoid) with diffuse and symptomatic disease when systemic therapy has failed to control symptoms.
  • 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.

A second radioembolization treatment (i.e., TheraSphere®, SIR-Spheres®) is considered medically necessary and, therefore, covered for new or progressive primary or metastatic liver cancers when all of the following criteria are met:
  • The individual has had a previous satisfactory response to a initial radioembolization treatment as evidenced on results of a computed tomography (CT) scan or positron emission tomograpry (PET)-CT scan performed 3 months following the previous procedure. Response should be graded according to the revised Response Evaluation Criteria In Solid Tumors (RECIST) guideline (Version 1.1).
  • The disease remains liver dominant.
  • The individual has a life expectancy of at least 3 months.
  • The individual's ECOG performance status is no greater than 2, or the individual has a Karnofsky Performance Status (KPS) of 70 or more.
  • There are no other effective systemic or liver-directed treatment options.
  • The individual has compensated liver function tests (LFTs).
  • The estimated lung dose and combined lung dose from previous embolizations are within acceptable dose volume constraints (i.e., the lung radiation dose is less than 25 to 30 Gy per treatment or less than 50 Gy cumulatively for all treatments).
  • Treatment for the disease is given to a targeted tumor volume.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for radioembolization, such as, but not limited to, neck (including parotid gland), pancreaticobiliary, anal, thymic, thyroid, endometrial, lung, kidney, gastric, small bowel, esophageal, ovarian, cervical, prostatic, bladder, sarcoma, and lymphoma malignancies are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

Third and subsequent radioembolization treatments and second and subsequent radioembolization procedure to the whole liver are considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

The use of radioembolization as a debulking agent and/or as a combined treatment with chemotherapy (adjuvant or concurrent) is considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

Radioembolization is used to treat unresectable hepatocellular carcinoma that is typically greater than 3 cm.
Radioembolization is generally used for individuals with the following indications:
  • Adequate functional status (ECOG 0-2)
  • Child Pugh score A or B
  • Liver-dominant metastases

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG Performance Status was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states: "These scales and criteria are used by doctors and researchers to assess how an individual's disease is progressing, access how the disease affects the daily living abilities of the individual, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

The Child-Pugh score

Note: The Child-Pugh score is calculated by adding the scores of the five factors and can range from 5 to 15. Child-Pugh class is A (a score of 5-6), B (7-9), or C (10 or above). Decompensation indicates cirrhosis with a Child-Pugh score of 7 or more (class B). This level has been the accepted criterion for listing for liver transplantation.

Factor
Units
1
2
3
Serum bilirubin
imol/L

mg/dL

< 34

< 2.0

34-51

2.0-3.0

>51

>3.0

Serum albumin
g/L

g/dL

>35

>3.5

30-35

3.0-3.5

< 30

< 3.0

Prothrombin time
Seconds prolonged

INR

0-4

< 1.7

4-6

1.7-2.3

>6

>2.3

Ascites
None
Easily controlled
Poorly controlled
Hepatic encephalopathy
None
Minimal
Advanced
Note: Table 163-3: Child-Pugh Classification of Cirrhosis : In Harrison's Manual of Medicine 17th ed.

KARNOFSKY PERFORMANCE STATUS (KPS) SCALE DEFINITIONS RATING (%) CRITERIA

The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses.

Able to carry on normal activity and to work; no special care needed.
  100  
Normal no complaints; no evidence of disease.
90
Able to carry on normal activity; minor signs or symptoms of disease.
80
Normal activity with effort; some signs or symptoms of disease.
Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.
70
Cares for self; unable to carry on normal activity or to do active work.
60
Requires occasional assistance, but is able to care for most personal needs.
50
Requires considerable assistance and frequent medical care.
Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.
40
Disabled; requires special care and assistance.
30
Severely disabled; hospital admission is indicated although death not imminent.
20
Very sick; hospital admission necessary; active supportive treatment necessary.
10
Moribund; fatal processes progressing rapidly.
0
Dead

References for KPS:

Crooks, V, Waller S, et al. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol. 1991; 46: M139-M144.

de Haan R, Aaronson A, et al. Measuring quality of life in stroke. Stroke. 1993; 24:320- 327.

Hollen PJ, Gralla RJ, et al. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Cancer. 1994; 73: 2087-2098.

O'Toole DM, Golden AM. Evaluating cancer patients for rehabilitation potential. West J Med. 1991; 155:384-387.

Oxford Textbook of Palliative Medicine, Oxford University Press. 1993;109.

Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: Reliability, validity, and guidelines. J Clin Oncology. 1984; 2:187-193.

http://www.hospicepatients.org/karnofsky.html. Accessed September 18, 2015.


BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, the use of SIR-Spheres® is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

Subject to the terms and conditions of the applicable benefit contract, devices that are used for the FDA-approved humanitarian device exemption (HDE) indications listed in this policy are covered under the medical benefits of the Company's products.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

SIR-Spheres® was approved by the FDA on March 5, 2002, for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intrahepatic artery chemotherapy (IHAC) of floxuridine (FUDR).

TheraSpheres® received a humanitarian device exemption (HDE) designation by the FDA on December 10, 1999, for radiation treatment or as a neoadjuvant to surgery or transplantation in individuals with unresectable hepatocellular carcinoma (HCC), including those individuals with a partial or branch portal vein thrombosis who can have placement of appropriately positioned hepatic arterial catheters.

Description

HEPATIC TUMORS

Hepatic tumors are classified as primary (i.e., they originate in the liver), the most common being hepatocellular carcinoma (HCC), or metastatic. Cholangiocarcinoma, the other type of primary liver cancer, can be divided into intrahepatic and extrahepatic diseases.

Hepatic cancers are virulent and difficult to treat. The treatment of choice is resection surgery; however, only 10 percent to 20 percent of individuals are eligible for surgery at the time of diagnosis. Other treatment options include systemic chemotherapy, hepatic artery embolization, and external beam radiation. Each has side effects and varying response rates.

RADIOEMBOLIZATION

Radioembolization (RE), also called selective internal radiation therapy or "SIRT" in past literature, involves the use of intrahepatic small beads or microspheres. Intrahepatic microspheres are radiolabeled particles composed of glass or resin polymers. The spheres are tagged with Yttrium-90 and are injected via a hepatic artery catheter to target radiation directly to liver tumors.

The hepatic circulation is uniquely organized: tumors greater than 0.5 cm rely on the hepatic artery for blood supply, whereas a normal liver is primarily perfused via the portal vein. Evidence suggests that the microspheres are selectively deposited in vascular tumor tissue, which allows much higher radiation doses without the resulting injury and morbidity caused by external beam radiation.

FDA-APPROVED INDICATIONS FOR RADIOEMBOLIZATION: UNRESECTABLE PRIMARY HEPATOCELLULAR CARCINOMA (HCC) AND UNRESECTABLE METASTATIC COLORECTAL CANCER

There are two types of Yttrium-90 microspheres approved by the US Food and Drug Administration (FDA): SIR-Spheres® (Sirtex Medical, San Diego, CA) and TheraSphere® (MDS, Nordion, Canada).

SIR-Spheres® received premarket approval from the FDA in March 2002 for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intrahepatic artery chemotherapy (IHAC) of floxuridine (FUDR). Treatment with SIR-Spheres® involves the placement of millions of polymer beads (microspheres) via a small catheter guided into the liver: the small spheres are injected into the liver tumor through the common hepatic (liver) artery or through the right or left hepatic artery. The spheres lodge in the area of the tumor, where the radiation helps slow the growth of the cancer cells. The radioactivity disappears within 11 days, but the spheres remain in the liver.

TheraSphere® received a Humanitarian Device Exemption (HDE) from the FDA in December 1999 for radiation treatment or as a neoadjuvant to surgery or transplantation in patients with unresectable hepatocellular carcinoma (HCC), including patients with a partial or branch portal vein thrombosis who have a hepatic arterial catheter in place and appropriately positioned for treatment. The indication to include those individuals with partial or branch portal vein thrombosis was made in 2007.

TheraSphere® is a low-toxicity liver cancer therapy that consists of millions of micro-glass beads containing radioactive Yttrium-90. The product is injected into the main artery of the individual’s liver through a catheter that allows the treatment to be delivered directly to the tumor via blood vessels.

Intrahepatic microspheres have been shown to prolong survival in primary and metastatic disease. Adverse effects are usually hepatic and gastrointestinal but are rarely severe in spite of radiation doses up to 150 GY (total amount of radiation measurement in units called Gray). In contrast, the highest external beam radiation dose that does not cause hepatic toxicity is only 30-35 GY.

UNRESECTABLE INTRAHEPATIC CHOLANGIOCARCINOMA AND UNRESECTABLE METASTATIC NEUROENDOCRINE TUMORS

The only curative approaches for the treatment of cholangiocarcinoma are surgery or transplantation, and these individuals may have poor prognosis even after surgery. Additionally, by the time the diagnosis for this disease is made, the majority of patients have unresectable cholangiocarcinoma. There is a lack of standardized treatment regimens for unresectable cholangiocarcinoma. The choices of treatment in those with unresectable cholangiocarcinoma involve systemic chemotherapy that may have partial efficacy, palliative biliary drainage and stenting (in extrahepatic cholangiocarcinoma), participation in a clinical trial exploring an unproven therapy (TheraSphere Microspheres are being investigated as a first-line therapy for cholangiocarcinoma), or locoregional therapies such as radioembolization. Evidence regarding safety and efficacy of treatment modalities such as radioembolization is very limited when this therapy is employed for unresectable cholangiocarcinoma. Unresectable intrahepatic cholangiocarcinoma may have slightly better outcomes than unresectable extrahepatic disease when locoregional therapies are administered. However, some evidence (consisting of pilot studies and small case series that explore radioembolization in preliminary assessments as a palliative option for cholangiocarcinoma) and clinical practices suggest that radioembolization may be offered only as a palliative option for unresectable cholangiocarcinoma.

In 2010, Cao et al reported on the outcomes of individuals with unresectable neuroendocrine liver metastases from two different hospitals treated with Yttrium-90 microspheres (SIR-Spheres) from 2003 to 2008. The data was examined retrospectively from a database. The response was assessed with radiographic evidence before and after radioembolization and measured by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Patients typically had a CT scan within 3 months of treatment and every 3 to 6 months until disease progression or death. Systemic chemotherapy was routinely given at one institution but not the other. Mean patient age at the time of radioembolization was 61 (range: 29-84 years), and 67% of patients were men. Primary tumor site was variable and included small bowel, pancreas, colon, thyroid, lung, and unknown. Median follow-up was 21 months (range 1-61 months). Fifty-one patients were evaluated, and six achieved a complete response, 14 a partial response, 14 had stable disease, and 17 had disease progression. Overall survival rates at 1, 2, and 3 years were 86%, 58%, and 47%, respectively. Median survival was 36 months (range: 1-61 months). Predictive factors for survival included extent of tumor involvement of the liver, radiographic response to treatment, presence of extrahepatic disease at the time of radioembolization, histological grade of tumor, and whether patients were responders (vs. nonresponders) to radioembolization.

Rhee et al reported the results of a multicenter, open-label Phase II study to assess the safety and efficacy of radioembolization, using glass or resin microspheres in 42 patients with metastatic neuroendocrine liver disease who had failed prior treatment(s), including medical (e.g., octreotide), surgical resection, bland or chemoembolization, and radiofrequency ablation or cryoablation. Mean patient age was 58 +/-12 years for glass and 61 +/-11 years for resin microspheres. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria was used to assess tumor response, which showed 92% of glass patients and 94% of resin patients were partial responders or had stable disease at 6 months after treatment. Median survival was 22 and 28 months for glass and resin, respectively.

Kennedy et al conducted a retrospective review of 148 patients from 10 institutions with unresectable hepatic metastases from neuroendocrine tumors who received resin microspheres. All patients had completed treatment of the primary tumor and metastatic disease and were not excluded based on prior therapy. Total number of resin microsphere treatments was 185, with retreatment in 22.3% of patients (19.6% received 2 treatments, and 2.7%, 3 treatments). All patients were followed with imaging studies at regular intervals to assess tumor response (using either WHO or RECIST criteria) until death, or they were censured if a different type of therapy was given after the microspheres. The male-to-female ratio was 49% to 51%, respectively, and median age was 58 years (range: 26-95 years). Median follow-up was 42 months. By imaging, response rates were stable disease, 22.7%; partial response, 60.5%; complete response, 2.7%; and progressive disease 4.9%. Hepatic and extrahepatic metastases contributed to death in the majority of patients, with 7% lost to follow-up. Median survival was 70 months. The authors conclude that radioembolization can deliver high doses of radiation preferentially to hepatic metastases from neuroendocrine tumors with encouraging response rates indicated by imaging and symptomatic improvement (although there were no data presented in the study regarding symptoms).

Additional case series in patients with treatment-refractory, unresectable neuroendocrine hepatic metastases have shown good tumor response and improvement in clinical symptoms with radioembolization.

The National Comprehensive Cancer Network (NCCN) considers the use of radioembolization for use in unresectable liver metastases a category 2B. Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Although no randomized trials are available, there is some suggestion that radioembolization for primary intrahepatic cholangiocarcinoma has response rates similar to those seen with standard chemotherapy. Radioembolization may play a role in individuals with unresectable tumors who are chemorefractory or unable to tolerate systemic chemotherapy. Current consensus from clinical experts supports the use of radioembolization for intrahepatic cholangiocarcinoma. Given the low likelihood of large scale clinical trials for this rare tumor, the available evidence is sufficient to conclude that radioembolization could be associated with improved outcomes for patients with primary intrahepatic cholangiocarcinoma.

UNRESECTABLE METASTATIC BREAST CANCER AND UNRESECTABLE METASTATIC MELANOMA

Similarly, for other tumors metastatic to the liver, including breast cancer and melanoma, the evidence consists of observational studies. Current consensus from clinical experts supports the use of radioembolization for the treatment of liver-dominant metastases from breast cancer and melanoma in individuals who are not candidates for or who have not responded to systemic therapies. Combined with the consensus from clinical experts, the available evidence is sufficient to conclude that radioembolization could be associated with improved outcomes for patients with hepatic metastases from breast cancer and melanoma with liver-dominant disease.

MISCELLANEOUS METASTATIC TUMORS

Small and very limited case reports have been published on the use of radioembolization in several other types of cancer with metastases, such as and neck (including parotid gland), pancreaticobiliary, anal, thymic, thyroid, endometrial, lung, kidney, gastric, small bowel, esophageal, ovarian, cervical, prostatic, bladder, sarcoma, and lymphoma. There are currently no national guidelines, such as those of the National Comprehensive Cancer Network (NCCN), for the use of radioembolization as a debulking agent. Furthermore, both the clinical effectiveness and toxicity of combined treatment with chemotherapy (adjuvant or concurrent) is not known.

REPEAT RADIOEMBOLIZATION

Consideration is now being given to repeating the procedure in an individual who has responded well previously, has good performance status, and has liver dominant disease without other treatment options. In their series of 148 individuals diagnosed with neuroendocrine tumor metastases to the liver treated with Yttrium-90 microspheres, Vyleta et al. (2011) noted a subgroup of 33 individuals who were retreated to the same liver lobe with very low toxicity and no evidence of radiation-induced liver disease (RILD). They also commented on other published studies in which a few individuals received repeat radioembolization of both or single lobes, with a few individuals even receiving a third treatment. In their analysis increased duration of tumor responses were noted and most deaths were attributed to progression of extrahepatic disease. Similarly, Lewandowski et al. (2006) noted further palliation and prolongation of survival in individuals retreated for viable residual or recurrent liver metastases. Favorable prognostic indicators for longer survival in their entire series of 82 initial and retreated individuals included a lower pretreatment level of alpha-fetoprotein (AFP) and a higher tumor to baseline uptake ratio.

Lam et al. (2013) attempted to correlate the occurrence of RILD in a population of 247 individuals treated to a targeted area with Yttrium-90 microspheres within univariate and multivariate analyses of multiple variables. This population included 8 individuals who were retreated. Two of these individuals received a second treatment to the whole liver and died shortly after the second treatment with signs and symptoms of RILD. Cumulative doses of 3.08 and 2.66 GBq were noted respectively. The remaining 6 individuals experienced minor side effects with cumulative doses of 2.41 to 3.88 GBq. Objective responses were noted in all individuals. Risk factor analysis disclosed repeat radioactive remobilization, serum total bilirubin and baseline serum aspartate aminotransferase as significant factors in the development of RILD but only repeat radioembolization proved to be an independent indicator. The authors noted objective tumor responses but commented on the need for improved safety limits which will require better dosimetric measurement.
References


Al-Adra DP, Gill RS, Axford SJ, et al. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: A systematic review and pooled analysis. Eur J Surg Oncol. Jan 2015;41(1):120-127.

Bangash AK, Atassi B, Kaklamani V, et al. 90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging response, survival. J Vasc Interv Radiol. 2007;18(5):621-628.

Boehm LM, Jayakrishnan TT, Miura JT, et al. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. Feb 2015;111(2):213-220.

Cao CQ, Yan TD, Bester L, et al. Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg. 2010;97(4):537-543.

Carr BI, Kondragunta V, Buch SC, et al. Therapeutic equivalence in survival for hepatic arterial
chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two cohort study. Cancer. Mar 1 2010;116(5):1305-1314.

Cianni R, Pelle G, Notarianni E, et al. Radioembolisation with (90)Y-labelled resin microspheres in the treatment of liver metastasis from breast cancer. Eur Radiol. Jan 2013;23(1):182-189.

Coldwell DM, Kennedy AS, Nutting CW. Use of yttrium-90 microspheres in the treatment of unresectable hepatic metastases from breast cancer. Int J Radiat Oncol Biol Phys. 2007;69(3):800-804.

Devcic Z, Rosenberg J, Braat AJ, et al. The efficacy of hepatic 90Y resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis. J Nucl Med. Sep 2014;55(9):1404-1410.

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan; 45(2):228-247.

El Fouly A, Ertle J, El Dorry A, et al. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. Feb 2015;35(2):627-635.

Eldredge-Hindy H, Ohri N, Anne PR, et al. Yttrium-90 microsphere brachytherapy for liver metastases from uveal melanoma: clinical outcomes and the predictive value of fluorodeoxyglucose positron emission tomography. Am J Clin Oncol. Jan 16 2014.

Engelman ES, Leon-Ferre R, Naraev BG, et al. Comparison of transarterial liver-directed therapies for low-grade metastatic neuroendocrine tumors in a single institution. Pancreas. Mar 2014;43(2):219-225.

Giammarile F, Bodei L, Chiesa C, et al. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. EJNMMI 2011;38(7):1393-1406.

Gonsalves CF, Eschelman DJ, Sullivan KL, et al. Radioembolization as salvage therapy for hepatic metastasis of uveal melanoma: a single-institution experience. Am J Roentgenol. 2011;196(2):468-473.

Gordon AC, Gradishar WJ, Kaklamani VG, et al. Yttrium-90 radioembolization stops progression of targeted breast cancer liver metastases after failed chemotherapy. J Vasc Interv Radiol. Oct 2014;25(10):1523-1532, 532 e1521-1522.

Gramenzi A, Golfieri R, Mosconi C, et al. Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis. Liver Int. Apr 22 2014.

Gray B, Van Hazel G, Hope M, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. Dec 2001;12(12):1711-1720.

Haug AR, Heinemann V, Bruns CJ, et al. 18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres. Eur J Nucl Med Mol Imaging. Jun 2011;38(6):1037-1045.

Haug AR, Tiega Donfack BP, Trumm C, et al. 18F-FDG PET/CT predicts survival after radioembolization of hepatic metastases from breast cancer. J Nucl Med. Mar 2012;53(3):371-377.

Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. Aug 10 2010;28(23):3687-3694.

Hoffmann RT, Paprottka PM, Schon A, et al. Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival. Cardiovasc Intervent Radiol. Feb 2012;35(1):105-116.

Ibrahim SM, Mulcahy MF, Lewandowski RJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 2008;113(8):2119-2128.

Jakobs TF, Hoffmann RT, Dehm K, et al. Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. J Vasc Interv Radiol. 2008;19(8):1187-1195.

Jakobs TF, Hoffmann RT, Fischer T, et al. Radioembolization in patients with hepatic metastases from breast cancer. J Vasc Interv Radiol. 2008;19(5):683-690.

Kalinowski M, Dressler M, König A, et al. Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study. Digestion. 2009;79(3):137-142.

Kalva SP, Rana RS, Liu R, et al. Yttrium-90 radioembolization as salvage therapy for liver metastases from colorectal cancer. Am J Clin Oncol. Nov 4 2014.

Kappadath SC. Yttrium-90 microsphere therapy planning and dose calculations. Presented at the American Association of Physicists in Medicine, Houston, TX. 2011 Aug 11. Accessed October 10th, 2016. Available at http://www.aapm.org/meetings/amos2/pdf/59-17214-40482-134.pdf.

Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65(2):412-425.

Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol. 2008;31(3):271-279.

Kennedy A, Nag S, Salem R, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys. May 1 2007;68(1):13-23.

Kennedy AS, Nutting C, Jakobs T, et al. A first report of radioembolization for hepatic metastases from ocular melanoma. Cancer Invest.2009;27(6):682-690.

Kennedy AS, Salem R. Radioembolization (yttrium-90 microspheres) for primary and metastatic hepatic malignancies. Cancer J. 2010;16(2):163-175.

King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008;113(5):921-929.

Klingenstein A, Haug AR, Zech CJ, et al. Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol. Feb 2013;36(1):158-165.

Kolligs FT, Bilbao JI, Jakobs T, et al. Pilot randomized trial of selective internal radiation therapy vs.chemoembolization in unresectable hepatocellular carcinoma. Liver Int. Nov 29 2014.

Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008;47(1-Jan):71-81.

Kulik L, Vouche M, Koppe S, et al. Prospective randomized pilot study of Y90+/-sorafenib as bridge to transplantation in hepatocellular carcinoma. J Hepatol. Aug 2014;61(2):309-317.

Kwok PC, Leung KC, Cheung MT, et al. Survival benefit of radioembolization for inoperable hepatocellular carcinoma using yttrium-90 microspheres. J Gastroenterol Hepatol. Nov 2014;29(11):1897-1904.

Lam MGEH, Louie JD, Iagaru AH, et al. Safety of repeated Yttrium-90 radioembolization. Cardiovasc Intervent Radiol. 2013 Oct; 36(5):1320-1328.

Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920-1928.

Lewandowski RJ, Memon K, Mulcahy MF, et al. Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy. Eur J Nucl Med Mol Imaging. Oct 2014;41(10):1861-1869.

Lewandowski RJ, Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Semin Intervent Radiol. 2006 Mar; 23(1):64-72.

Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet. 2002;359(9319):1734-1739.

Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial). J Clin Oncol. 2007;25(18S):LBA1.

Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164-1171.

Memon K, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys. Jul 1 2012;83(3):887-894.

Michl M, Haug AR, Jakobs TF, et al. Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors. Oncology. 2014;86(1):24-32.

Mouli S, Memon K, Baker T, et al. Yttrium-90 radioembolization for intrahepatic cholangiocarcinoma: safety, response, and survival analysis. J Vasc Interv Radiol. Aug 2013;24(8):1227-1234.

Mulcahy MF, Lewandowski RJ, Ibrahim SM, et al. Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer. 2009;115(9):1849-1858.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines: Colon Cancer v2.2015. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed October 10th, 2016.

Network NCC. NCCN Clinical Practice Guidelines in Oncology. Colon Cancer. Version 2.2015.
http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Accessed October 10th, 2016.

Network NCC. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2015. http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed October 10th, 2016.

Network NCC. NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 2.2015. http://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed October 10th, 2016.

Network NCC. NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 3.2015. http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf. Accessed October 10th, 2016.

Network NCC. NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine Tumors. Version 1.2015. http://www.nccn.org/professionals/physician_gls/PDF/neuroendocrine.pdf. Accessed October 10th, 2016.

Paprottka PM, Hoffmann RT, Haug A, et al. Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres. Cardiovasc Intervent Radiol. Apr 2012;35(2):334-342.

Peker A, Cicek O, Soydal C, et al. Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases. Diagn Interv Radiol. Jan-Feb 2015;21(1):54-59.

Piduru SM, Schuster DM, Barron BJ, et al. Prognostic value of 18f-fluorodeoxyglucose positron emission tomography-computed tomography in predicting survival in patients with unresectable metastatic melanoma to the liver undergoing yttrium-90 radioembolization. J Vasc Interv Radiol. Jul 2012;23(7):943-948.

Pitton MB, Kloeckner R, Ruckes C, et al. Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma. Cardiovasc Intervent Radiol. Nov 7 2014.

Ramanathan R, Sharma A, Lee DD, et al. Multimodality Therapy and Liver Transplantation for Hepatocellular Carcinoma: A 14-Year Prospective Analysis of Outcomes. Transplantation. Feb 5 2014.

Rayar M, Sulpice L, Edeline J, et al. Intra-arterial Yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment. Ann Surg Oncol. Jan 27 2015.

Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y radioembolization for metastatic neuroendocrine liver tumors: Preliminary results from a multi-institutional experience. 2008;247(6):1029-1035.

Rosenbaum CE, Verkooijen HM, Lam MG, et al. Radioembolization for treatment of salvage patients with colorectal cancer liver metastases: a systematic review. J Nucl Med. Nov 2013;54(11):1890-1895.

Ruutiainen AT, Soulen MC, Tuite CM, et al. Chemoembolization and bland embolization of neuroendocrine tumor netastases to the liver. J Vasc and Interven Radiology. 2007 Jul; 18(7):847-855.

Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138(1):52-64.

Salem R, Thurston KG, Carr BI, et al. Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. J Vasc Interv Radiol. 2002;13(9 pt 2):S223-229.

Saxena A, Bester L, Shan L, et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol. Dec 7 2013.

Saxena A, Bester L, Chua TC, et al. Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol. Feb 2010;17(2):484-491.

Saxena A, Meteling B, Kapoor J, et al. Is Yttrium-90 radioembolization a viable treatment option for unresectable, chemorefractory colorectal cancer liver metastases? A large single-center experience of 302 patients. Ann Surg Oncol. Oct 17 2014.

Saxena A, Kapoor J, Meteling B, et al. Yttrium-90 radioembolization for unresectable, chemoresistant breast cancer liver metastases: a large single-center experience of 40 patients. Ann Surg Oncol. Apr 2014;21(4):1296-1303.

Saxena A, Meteling B, Kapoor J, et al. Yttrium-90 radioembolization is a safe and effective treatment for unresectable hepatocellular carcinoma: A single centre experience of 45 consecutive patients. Int J Surg. Dec 2014;12(12):1403-1408.

Seidensticker R, Denecke T, Kraus P, et al. Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol. Oct 2012;35(5):1066-1073.

Smits ML, Prince JF, Rosenbaum CE, et al. Intra-arterial radioembolization of breast cancer liver metastases: a structured review. Eur J Pharmacol. Jun 5 2013;709(1-3):37-42.

Tice J. Selective internal radiation therapy or radioembolization for inoperable liver metastases from colorectal cancer California Technology Assessment Forum 2010;
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Tohme S, Sukato D, Chen HW, et al. Yttrium-90 radioembolization as a bridge to liver transplantation: a singleinstitution experience. J Vasc Interv Radiol. Nov 2013;24(11):1632-1638.

Townsend A, Price T, Karapetis C. Selective internal radiation therapy for liver metastases from colorectal cancer. Cochrane Database Syst Rev. 2009(4):CD007045.

Van HG, Blackwell A, Anderson J, et al. Randomized phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88(2):78-85.

Vente MA, Wondergem M, van der Tweel I, et al. Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol. Apr 2009;19(4):951-959.

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Vyleta M and Coldwell D. Radioembolization in the treatment of neuroendocrine tumor metastases to the liver. Int J Hepatology. 2011. Accessed October 10th, 2016. Available at: http://www.hindawi.com/journals/ijh/2011/785315/

Xing M, Prajapati HJ, Dhanasekaran R, et al. Selective internal Yttrium-90 radioembolization therapy (90YSIRT) versus best supportive care in patients with unresectable metastatic melanoma to the liver refractory to systemic therapy: safety and efficacy cohort study. Am J Clin Oncol. Aug 7 2014.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

37243, 75894, 77778, 79445


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

C22.0 Liver cell carcinoma

C22.1 Intrahepatic bile duct carcinoma

C22.8 Malignant neoplasm of liver, primary, unspecified as to type

C22.9 Malignant neoplasm of liver, not specified as primary or secondary

C24.0 Malignant neoplasm of extrahepatic bile duct

C24.8 Malignant neoplasm of overlapping sites of biliary tract

C24.9 Malignant neoplasm of biliary tract, unspecified

C78.7 Secondary malignant neoplasm of liver and intrahepatic bile duct

C78.80 Secondary malignant neoplasm of unspecified digestive organ

C78.89 Secondary malignant neoplasm of other digestive organs

C7B.02 Secondary carcinoid tumors of liver

D01.5 Carcinoma in situ of liver, gallbladder and bile ducts

E34.0 Carcinoid syndrome



HCPCS Level II Code Number(s)



Q3001 Radioelements for brachytherapy, any type, each

S2095 Transcatheter occlusion or embolization for tumor destruction, percutaneous, any method, using yttrium-90 microspheres

Healthcare Common Procedure Coding System (HCPCS) C Series Codes can only be reported for outpatient facility services. Professional providers should not report HCPCS C Series Codes for professional services regardless of where those services are performed:

C2616 Brachytherapy source, nonstranded, yttrium-90, per source



Revenue Code Number(s)

N/A

Coding and Billing Requirements



Policy History

Revisions from 09.00.48f
09/12/2018The policy has been reviewed and reissued to communicate the Company’s continuing position on Radioembolization for Primary and Metastatic Tumors of the Liver (Independence Administrators).


Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 01/01/2016
Version Issued Date: 12/31/2015
Version Reissued Date: 09/12/2018

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