Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1)    Some non surgical treatment of liver cancers and metastases require pre-authorization.

2)    Several different forms of treatment are used to treat liver tumors that are not possible to treat with surgery.

All of the following procedures require pre-authorization with a diagnosis of liver cancer (C22.0 – C22.9, C78.7):

1. Percutaneous Ethanol Injection

Percutaneous ethanol injection (PEI) is considered medically necessary for the treatment of hepatocellular cancers (HCC) without extrahepatic spread.

1. Chemoembolization

Chemoembolization (CE, TACE) is considered medically necessary for any of the following:

1. For symptomatic treatment of functional neuroendocrine cancers (i.e., carcinoid tumors and pancreatic endocrine tumors) involving the liver. For carcinoid tumors, TACE is considered medically necessary only in persons who have failed systemic therapy with octreotide to control carcinoid syndrome (e.g., debilitating flushing, wheezing and diarrhea); or
2. For unresectable, primary HCC; or
3. As a bridge to transplant in patients with hepatocellular cancer where the intent is to prevent further tumor growth and to maintain a patient’s candidacy for liver transplant when  all of the following patient characteristics apply:

·      A single tumor less than 5cm or no more than 3 tumors each less than 3 cm in size, AND

·      Absence of extrahepatic disease or vascular invasion, AND

·      Child-Pugh score of either A or B.  See http://depts.washington.edu/uwhep/calculations/childspugh.htm

3.    Intra-hepatic Chemotherapy

Intra-hepatic chemotherapy (infusion) is considered medically necessary for members with liver metastases from colorectal cancer.

4.    Intra-hepatic Microspheres

Intra-hepatic microspheres (e.g., TheraSphere, MDS Nordion Inc.; SIR-Spheres, Sirtex Medical Inc., San Diego, CA) are considered medically necessary for any of the following:

1. For symptomatic treatment of functional neuroendocrine cancers (i.e., carcinoid tumors and pancreatic endocrine tumors) involving the liver. For carcinoid tumors, intrahepatic microspheres are considered medically necessary only in persons who have failed systemic therapy with octreotide to control carcinoid syndrome (e.g., debilitating flushing, wheezing and diarrhea); or
2. For unresectable, primary HCC;

i.      Tumor volume is < 50% of the target liver volume

ii.    Child-Pugh grade A (no ascites, bilirubin < 2 mg/dL, albumin > 3.5 g/dL, prothrombin time < 4 seconds over control, INR < 1.7, no encephalopathy)

iii.   There are no extrahepatic metastases

iv.   ECOG performance status of 0 – 2 (Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.); or

C.   For unresectable liver tumors from primary colorectal cancer that has failed first line and second line standard chemotherapy.

i.      There is minimal or no extra-hepatic disease

ii.    Tumor volume is 50% or less of total liver volume

iii.   Bilirubin is less than 3 mg/dL

iv.   ECOG performance status of 0 – 2

Intra-hepatic microspheres are considered experimental and investigational for other indications.

1. Cryosurgery, Microwave, Radiofrequency or Radiopharmaceutical (such as yttrium-90) Ablation

Cryosurgery, microwave, or radiofrequency ablation is considered medically necessary for:

1. Isolated colorectal cancer liver metastases or isolated hepatocellular cancer who are not candidates for open surgical resection and who meet the following criteria:

i.      Ablation is being performed with curative not palliative intent.

ii.    Members must either have hepatic metastases from a colorectal primary cancer or have a hepatocellular cancer; and

iii.   Members must have isolated liver disease. Members with nodal or extra-hepatic systemic metastases are not considered candidates for these procedures; and

iv.   All tumors in the liver, as determined by preoperative imaging, would be potentially destroyed by cryotherapy, microwave, or radiofrequency ablation; and 

v.    Because open surgical resection is the preferred treatment, members must be unacceptable open surgical candidates due to the location or extent of the liver disease or due to co-morbid conditions such that the member is unable to tolerate an open surgical resection; and

vi.   Liver lesions must be 4 cm or less in diameter and occupy less than 50% of the liver parenchyma. Lesions larger than this may not be adequately treated by either procedure.

1. Unresectable neuroendocrine tumors metastatic to the liver.

Codes Used In This BI:

1.     Percutaneous ethanol injection (PEI) for other liver neoplasms is considered experimental and investigational when criteria are not met. There is inadequate information to document the effectiveness of PEI as an alternative to surgical resection for the treatment of hepatic metastases. 

2.     Combined radiofrequency ablation and PEI is considered experimental and investigational for the treatment of HCC.

3.     Chemoembolization is considered experimental and investigational for palliative treatment of liver metastases from other non-neuroendocrine primaries (e.g., colon cancer, melanoma, or unknown primaries) because there is inadequate evidence in the medical literature of the effectiveness of CE for these indications.

4.     Intra-hepatic chemotherapy is considered experimental and investigational for treatment of liver primaries or metastases from other primaries besides colorectal cancer.

5.      “One-shot” arterial chemotherapy for members with liver metastases from colorectal cancer is considered experimental and investigational.

6.     Transarterially administered gene therapy is considered experimental and investigational for primary and secondary liver malignancies.

7.     Drug-eluting beads trans-arterial chemoembolization are considered experimental and investigational for primary and liver-dominant metastatic disease of the liver.

8.     Cryosurgical, microwave, or radiofrequency ablation as a treatment of hepatic metastases from non-colonic primary cancers is considered experimental and investigational.

9.     Cryosurgical, microwave or radiofrequency ablation as a palliative treatment of either hepatic metastases from colorectal cancer or hepatocellular cancer is also considered experimental and investigational.

Percutaneous Ethanol Injection

1. Büchner-Steudel P, Behl S, Fleig WE. Percutaneous ethanol injection or percutaneous acetic acid injection for hepatocellular carcinoma (Protocol for Cochrane Review). Cochrane Database Systematic Rev. 2007 ;( 3):CD003779. 
2. Masaki T, Morishita A, Kurokohchi K, Kuriyama S. Multidisciplinary treatment of patients with hepatocellular carcinoma. Expert Rev Anticancer Ther. 2006; 6(10):1377-1384.
3. Brunello F, Veltri A, Carucci P, et al. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial. Scand J Gastroenterol. 2008; 43(6):727-735.
4. Wong SN, Lin CJ, Lin CC, et al. Combined percutaneous radiofrequency ablation and ethanol injection for hepatocellular carcinoma in high-risk locations. AJR Am J Roentgenol. 2008; 190(3):W187-W195.
5. Schoppmeyer K, Weis S, Mössner J, Fleig WE. Percutanous ethanol injection or percutaneous acetic acid injection for early hepatocellular carcinoma. Cochrane Database Syst Rev. 2009 ;( 3):CD006745.

Chemoembolization

1. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation, or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet. 2002; 359:1734-1739.
2. Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol. 2002; 13(9 Pt 2):S211-S221.
3. Oliveri RS, Gluud C. Transcatheter arterial embolisation and chemoembolisation for hepatocellular carcinoma (Protocol for Cochrane Review). Cochrane Database Systematic Rev. 2004 ;( 2):CD004787.
4. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003; 37(2):429-442.
5. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-analysis of randomized controlled trials. Radiology. 2002; 224(1):47-54. 
6. Marelli L, Stigliano R, and Triantos C, et al. Transarterial therapy for hepatocellular carcinoma: Which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 2007; 30(1):6-25.
7. Pleguezuelo M, Marelli L, Misseri M, et al. TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther. 2008; 8(10):1623-1641.

Intra-hepatic Chemotherapy (Infusion) for Liver Malignancies

1. Okada S. Chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1998; 45 (Suppl 3):1259-1263.
2. Sakai Y, Izumi N, Tazawa J, et al. Treatment for advanced hepatocellular carcinoma by transarterial chemotherapy using reservoirs or one-shot arterial chemotherapy. J Chemother. 1997; 9(5):347-351.
3. Soga K, Nomoto M, Ichida T, et al. Clinical evaluation of Transcatheter arterial embolization and one-shot chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1988; 35(3):116-120.
4. ES-Y, Chow PK-H, Tai B-C, et al. Neoadjuvant and adjuvant therapy for operable hepatocellular carcinoma. Cochrane Database Systematic Rev. 1999 ;( 3):CD001199.
5. Nordlinger B, Rougier P. Nonsurgical methods for liver metastases including cryotherapy, radiofrequency ablation, and infusional treatment: What`s new in 2001? Curr Opin Oncol. 2002; 14(4):420-423.
6. Mocellin S, Pilati P, Lise M, Nitti D. Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: The end of an era? J Clin Oncol. 2007; 25(35):5649-5654.
7. Kalva SP, Thabet A, Wicky S. Recent advances in transarterial therapy of primary and secondary liver malignancies. Radiographic. 2008; 28(1):101-117.

Intrahepatic Microspheres (TheraSphere, SIR-Sphere)

1. Sato K, Lewandowski RJ, Bui JT, et al. Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): Assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol. 2006; 29(4):522-529.
2. Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: Down staging to resection, RFA, and bridge to transplantation. J Surg Oncol. 2006; 94(7):572-586.
3. Allison C. Yttrium-90 microspheres (TheraSphere® and SIR-Spheres®) for the treatment of unresectable hepatocellular carcinoma. Issues in Emerging Health Technologies Issue 102. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; September 2007. Available at: http://www.cadth.ca/media/pdf/E0038_TheraSphere_cetap_e.pdf. Accessed March 28, 2011.
4. Sato KT, Lewandowski RJ, Mulcahy MF, et al. Unresectable chemo refractory liver metastases: Radio embolization with 90Y microspheres--safety, efficacy, and survival. Radiology. 2008; 247(2):507-515.
5. National Comprehensive Cancer Network (NCCN). Neuroendocrine tumors. NCCN Clinical Practice Guidelines in Oncology. V.2.2009. Fort Washington, PA: NCCN; 2009.
6. Vente MA, Wondergem M, van der Tweel I, et al. Yttrium-90 microsphere radio embolization for the treatment of liver malignancies: A structured meta-analysis. Eur Radiol. 2009; 19(4):951-959.
7. Townsend A, Price T, Karapetis C. Selective internal radiation therapy for liver metastases from colorectal cancer. Cochrane Database Syst Rev. 2009 ;( 4):CD007045.
8. Tice JA. Selective internal radiation therapy or radio embolization for inoperable liver metastases from colorectal cancer. A Technology Assessment. San Francisco, CA: California Technology Assessment Forum (CTAF); February 17, 2010.

Drug-Eluting Beads Trans-Arterial Chemoembolization

1. Poon RT, Tso WK, Pang RW, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol. 2007; 5(9):1100-1108.
2. Malagari K, Chatzimichael K, Alexopoulou E, et al. Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: Results of an open-label study of 62 patients. Cardiovasc Intervent Radiol. 2008; 31(2):269-280.
3. Stewart C, Martin RCG. Drug-eluting bead therapy in primary and metastatic disease of the liver. HPB. 2009; 11(7):541-550.
4. Fiorentini G, Aliberti C, Del Conte A, et al. Intra-arterial hepatic chemoembolization (TACE) of liver metastases from ocular melanoma with slow-release irinotecan-eluting beads. Early results of a phase II clinical study. In Vivo. 2009; 23(1):131-137.
5. Martin RC, Robbins K, Tomalty D, et al. Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: An interim report. World J Surg Oncol. 2009; 7:80.
6. Guiu B, Colin C, Cercueil JP, et al. Pilot study of transarterial chemoembolization with pirarubicin and amiodarone for unresectable hepatocellular carcinoma. Am J Clin Oncol. 2009; 32(3):238-244.
7. Tokh M, Nugent FW, Molgaard C, et al. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) in hepatocellular carcinoma (HCC): A large single-institution experience. 2010 Gastrointestinal Cancers Symposium, Abstract No. 248. Available at: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72&abstractID=1818. Accessed March 28, 2011.

Ablation

1. Seki T, Wakabayashi M, Nakagawa T, et al. Percutaneous microwave coagulation therapy for patients with small hepatocellular carcinoma: Comparison with percutaneous ethanol injection therapy. Cancer. 1999; 85:1694–1702.
2. Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: Comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology. 2002; 223:331–337.
3. Liang P, Dong B, Yu X, et al. Prognostic factors for survival in patients with hepatocellular carcinoma after percutaneous microwave ablation. Radiology. 2005; 235:299–307.
4. Ajisaka H, Miwa K. Acute respiratory distress syndrome is a serious complication of microwave coagulation therapy for liver tumors. Am J Surg. 2005; 189:730–733.
5. National Institute for Health and Clinical Excellence (NICE). Microwave ablation for treatment of metastases in the liver. Interventional Procedure Guidance 220. London, UK: NICE; May 2007.
6. National Institute for Health and Clinical Excellence (NICE). Microwave ablation of hepatocellular carcinoma. Interventional Procedure Guidance 214. London, UK: NICE; March 2007.
7. National Comprehensive Cancer Network (NCCN). Hepatobiliary cancers. NCCN Clinical Practice Guidelines in Oncology. V.1.2007. Jenkintown, PA: NCCN; 2007.
8. National Comprehensive Cancer Network (NCCN). Colon cancer. NCCN Clinical Practice Guidelines in Oncology. V.2.2007. Jenkintown, PA: NCCN; 2007.
9. Kornprat P, Jarnagin WR, DeMatteo RP, et al. Role of intraoperative thermoablation combined with resection in the treatment of hepatic metastasis from colorectal cancer. Arch Surg. 2007; 142(11):1087-1092.
10. Siperstein AE, Berber E, Ballem N, Parikh RT. Survival after radiofrequency ablation of colorectal liver metastases: 10-year experience. Ann Surg. 2007; 246(4):559-565; discussion 565-567.
11. Al-asfoor A, Fedorowicz Z, Lodge M. Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases. Cochrane Database Syst Rev. 2008 :( 2):CD006039.
12. Brunello F, Veltri A, Carucci P, et al. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial. Scand J Gastroenterol. 2008; 43(6):727-735.
13. Garrean S, Hering J, Saied A, et al. Radiofrequency ablation of primary and metastatic liver tumors: A critical review of the literature. Am J Surg. 2008; 195(4):508-520.
14. Lau WY, Lai EC. The current role of radiofrequency ablation in the management of hepatocellular carcinoma: A systematic review. Ann Surg. 2009; 249(1):20-25.
15. National Comprehensive Cancer Network (NCCN). Neuroendocrine tumors. NCCN Clinical Practice Guidelines in Oncology v.2.2009. Fort Washington, PA: NCCN; 2009.
16. Stang A, Fischbach R, Teichmann W, et al. A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases. Eur J Cancer. 2009; 45(10):1748-1756.
17. Wong SL, Mangu PB, Choti MA, et al. American Society of Clinical Oncology 2009 clinical evidence review on radiofrequency ablation of hepatic metastases from colorectal cancer. J Clin Oncol. 2010; 28(3):493-508.

This policy applies to all health plans and products administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet.  Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) or Certificate of Coverage (COC) for those plans or products insured by QualChoice.  In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC or COC, the SPD, EOC, or COC, as applicable, will prevail.  State and federal mandates will be followed as they apply.