BlueCross BlueShield of Tennessee Medical Policy Manual

Chemoembolization for the Treatment of Surgically Unresectable Hepatocellular Carcinoma

DESCRIPTION

Transcatheter arterial chemoembolization (TACE) was developed as an alternative to conventional systemic or intra-arterial chemotherapy. TACE has been investigated as a treatment of isolated liver metastases and for hepatocellular carcinoma.

The rationale for TACE is that infusions of viscous material will occlude arterial blood, causing an infarct and subsequent necrosis of tumors in the infarcted region. The cytotoxic effect of arterial occlusion can be potentiated by labeling the infusion with radioactive isotopes or by adding cytotoxic drugs. The liver is especially amenable to such an approach given the distinct lobular anatomy of the liver, the existence of two independent blood supplies, and the ability of healthy hepatic tissue to compensate for tissue mass lost during chemoembolization. Another rationale is that TACE provides for effective local dose intensity while avoiding systemic toxicities associated with intravenous chemotherapy. However, TACE of the liver is associated with its own constellation of potentially life-threatening toxicities and complications, such as severe postembolization syndrome, hepatic insufficiency, abscess, or infarction.

The chemoembolization procedure requires hospitalization. Prior to the procedure, the patency of the portal vein must be demonstrated in order to ensure an adequate post-treatment hepatic blood supply. Under local anesthesia and mild sedation, a superselective catheter is inserted via the femoral artery and threaded into the hepatic artery. Angiography is then performed to delineate the hepatic vasculature, followed by injection of the embolic chemotherapy mixture. Embolic material varies, but may include a viscous collagen agent, polyvinyl alcohol particles, or ethiodized oil. Typically, only one lobe of the liver is treated during a single session, with subsequent embolization procedures scheduled from 5 days to 6 weeks later. In addition, since the embolized vessel recanalizes, chemoembolization can be repeated as many times as necessary.

Note: This policy does not address the use of transcatheter hepatic arterial chemoembolization as a bridge to liver transplantation.

POLICY

Transcatheter hepatic arterial chemoembolization for the treatment of surgically unresectable hepatocellular carcinoma is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)

Transcatheter hepatic arterial chemoembolization, for all other indications, is considered investigational.

MEDICAL APPROPRIATNESS

Transcatheter hepatic arterial chemoembolization is considered medically appropriate if all of the following criteria are met:

• Performance status must be good per a standardized performance assessment tool (e.g., Karnofsky Performance Scale, Short Form 36 Performance Scale); and

• Individual must have normal, Child's A, or Child's B liver function; and

• Individual must have a negative metastatic evaluation (should included negative chest x-ray, CT or MRI of the abdomen); and

• Individual should have multiple or extensive hepatocellular carcinoma tumors of the liver; and

• Patency of the portal vein must be demonstrated prior to the procedure.

ADDITIONAL INFORMATION

Childs-Turcotte-Pugh (CTP) score is a scoring system for liver function based on the presence of encephalopathy and/or ascites, and laboratory measures of bilirubin, albumin, and prothrombin time.

There is lack of randomized controlled trials that provide evidence of the efficacy of transcatheter hepatic arterial chemoembolization for other indications.

Transcatheter hepatic arterial chemoembolization, for all other indications, does not meet the following technology evaluation criteria:

• The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.

• The technology must improve the net health outcome.

• The technology must be as beneficial as any established alternatives.

SOURCES

American Association for the Study of Liver Diseases. (2003). Pre-transplant adjuvant therapy with TACE for hepatocellular carcinoma results in a significant survival disadvantage. Retrieved June 14, 2005 from http://www.hivandhepatitis.com/2003icr/03_assld/docs/1208/120803_hcv_c.html.

Bambha, K., Kim, W. R., Kremers, W. K., Therneau, T. M., Kamath, P. S., Wiesner, R., et al. (2004). Predicting survival among patients listed for liver transplantation: An assessment of serial MELD measurements. American Journal of Transplantation, 4 (11), 1798-1804. Abstract retrieved June 14, 2005 from PubMed database.

Battula, N., Srinivasan, P., Madanur, M., Chava, S. P., Priest, O., Rela, M et al. (2007). Ruptured hepatocellular carcinoma following chemoembolization: A western experience. Hepatobiliary and Pancreatic Diseases International, 6 (1), 49-51. Retrieved April 25, 2007 from PubMed database.

Befeler, A. S. (2005). Chemoembolization and bland embolization: A critical appraisal. Clinics in Liver Disease, 9, 287-300.

BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2006). Transcatheter arterial chemoembolization as a treatment for primary or metastatic liver malignancies (8.01.11). Retrieved April 23, 2007 from BlueWeb.

BlueCross BlueShield of Tennessee network providers. July-August 2005.

Cormier, J. N., Thomas, K. T., Chari, R. S., & Pinson, C. W. (2006). Management of hepatocellular carcinoma. Journal of Gastrointestional Surgery, 10 (5), 761-780. Retrieved April 25, 2007 from PubMed database.

Decaens, T., Roudot-Thoraval, F., Bresson-Hadni, S., Meyer, C., Gugenheim, J., Durand, F., et al. (2005). Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transplantation, 11 (7), 767-775. Abstract retrieved June 14, 2005 from PubMed database.

ECRI Institute. Health Technology Information Service. Custom Hotline Response. (2006, February). Transcatheter arterial chemoembolization (TACE) for liver cancer. Retrieved April 25, 2007 from ECRI Institute.

Feldman, M., Friedman, L. S., and Sleisenger, M. H. (Eds.). (2002). Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management (7th ed., pp. 2162-2163). St. Louis: W. B. Saunders Company.

Fisher, R. A., Maluf, D., Cotterell, A. H., Stravitz, T., Wolfe, L., Luketic, V., et al. (2004). Non-resective ablation therapy for hepatocellular carcinoma: Effectiveness measured by intention-to-treat and dropout from liver transplant waiting list. Clinical Transplantation, 18 (5), 502-512. Abstract retrieved June 14, 2005 from PubMed database.

Graziadei, I. W., Sandmueller, H., Waldenberger, P., Koenigsrainer, A., Nachbaur, K., Jaschke, W., et al. (2003). Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transplantation, 9 (6), 557-563. Abstract retrieved June 14, 2005 from Wiley Interscience database.

Hayashi, P. H., Ludkowski, M., Forman, L. M., Osgood, M., Johnson, S., Kugelmas, M., et al. (2004). Hepatic artery chemoembolization for hepatocellular carcinoma in patients listed for liver transplantation. American Journal of Transplantation, 4 (5), 782-787. Abstract retrieved June 14, 2005 from PubMed database.

Health Technology Assessment Information Service. Health Technology Forecast. (2003). Chemoembolization for in operable liver tumors. Retrieved June 14, 2005 from ECRI HTAIS.

Health Technology Assessment Information Service. Health Technology Forecast. (2005). Liver cancer. Retrieved August 12, 2005 from ECRI HTAIS.

Health Technology Assessment Information Service. Health Technology Trends. (2002). Chemoembolization extends survival significantly for inoperable liver cancer. Retrieved August 12, 2005 from ECRI HTAIS.

Moreno Planas, J., Lopez Monclus, J., Gomez Cruz, A., Rubio Gonzalez, E., Perez Aranguena, R., Boullosa Grana, E., et al. (2005). Efficacy of hepatocellular carcinoma locoregional therapies on patients waiting for liver transplantation. Transplant Proceedings, 37 (3), 1484-5. Abstract retrieved June 14, 2005 from PubMed database.

Ramsey, D. E., Kernagis, L. Y., Soulen, M. C., Geschwind, J. H. (2002). Chemoembolization of hepatocellular carcinoma. Journal of Vascular and Interventional Radiology, 13, S211-S221.

Rose, D. M., Chapman, W. C., Brockenbrough, A. T., Wright, K., Rose, A. T., Meranze, S., et al. (1999). Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma. The American Journal of Surgery, 177 (5), 405-410.

Ryder, S. D. (2003). Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. GUT, 52 (Suppl. III), iii1-iii8.

Sasaki, A., Iwashita, Y., Shibata, K., Ohta, M., Kiano, S. & Mori, M. (2006). Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma. European Journal of Surgical Oncology, 32 (7), 773-779. Retrieved April 25, 2007 from PubMed database.

Sherman, M., Takayama, Y. (2004). Screening and treatment for hepatocellular carcinoma. Gastroenterology Clinics of North America, 33, 671-691.

Sotiropoulos, G. C., Malago, M., Molmenti, E., Paul, A., Nadalin, S., Brokalaki, E. I., et al. (2005). Efficacy of transarterial chemoembolization prior to liver transplantation for hepatocellular carcinoma as found in pathology. Hepatogastroenterology, 52 (62), 329-32. Abstract retrieved June 14, 2005 from PubMed database.

Technology Evaluation Center. (2001, March). Transcatheter arterial chemoembolization of hepatic tumors (Vol. 15, No. 22). Washington, DC: BlueCross BlueShield Association.

Wong, L. L., Tanaka, K., Lau, L., Komura, S. (2004). Pre-transplant treatment of hepatocellular carcinoma: Assessment of tumor necrosis in explanted livers. Clinical Transplantation, 18 (3), 227-234. Abstract retrieved June 14, 2005 from PubMed database.

Yao, F. Y., Kinkhabwala, M. C., LaBerge, J. M., Bass, N. M., Brown, R. Jr., Kerlan, R., et al. (2005). The impact of pre-operative logo-regional therapy on outcome after liver transplantation for hepatocellular carcinoma. American Journal of Transplantation, 5 (4), 795-804. Abstract retrieved June 14, 2005 from PubMed database.

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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