Isolated Limb Perfusion/Infusion for Malignant Melanoma
DESCRIPTION
Isolated limb perfusion (ILP) is a method of drug delivery that is designed to deliver high local doses of chemotherapy while avoiding systemic toxicity. It has been investigated primarily as a treatment of malignant melanoma arising in the extremities. ILP involves the following steps: 1) mobilization and placement of venotomy and arteriotomy catheters into the major blood vessels (axillary, brachial, iliac, or popliteal artery and vein) proximal to the tumor; 2) isolation of the limb via a tourniquet; and 3) perfusion of a chemotherapeutic drug via an extracorporeal circulation system into the affected extremity. Perfusion lasts for approximately 60 minutes.
Melphalan is the drug typically used, but more recently melphalan has been combined with tumor necrosis factor (TNF) and/or interferon gamma. ILP has also been performed in conjunction with mild hyperthermia based on the theoretical rationale that heat may potentiate the tumor killing effect of melphalan. Hyperthermia is performed by warming the perfusate and by wrapping the treated extremity in a warming blanket. Target tissue temperature is typically 39 to 40 degrees Celsius.
ILP as a treatment of melanoma has been investigated in two general settings - either as an adjuvant treatment after all clinical evidence of melanoma has been surgically resected, or as a therapeutic treatment for individuals with surgically unresectable melanoma. The adjuvant setting can be further broken down into its use after initial resection of primary melanoma considered to be at high risk for recurrence, or its use after resection of local recurrences, frequently referred to as satellite lesions or "in transit" melanoma.
POLICY
Isolated limb perfusion/infusion for the treatment of malignant melanoma is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Isolated limb perfusion as an adjunct treatment of surgically treated locally recurrent melanoma with no other evidence of disease is considered investigational.
Isolated limb perfusion/infusion using melphalan in conjunction with other agents, including, but not limited to, the following: tumor necrosis factor (TNF) or interferon gamma is considered investigational.
Isolated limb perfusion as adjuvant treatment of surgically treated primary malignant melanoma is considered not medically necessary.
MEDICAL APPROPRIATENESS
Isolated limb perfusion/infusion for the treatment of malignant melanoma is considered medically appropriate if ALL of the following:
The treatment uses melphalan as a single agent
The treatment is in conjunction with normothermia or hyperthermia
The individual has local recurrence of non-resectable melanoma (i.e., satellite lesions or "in transit" melanoma)
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
Individuals typically undergo one treatment with isolated limb perfusion. Some individuals with incomplete response after the first procedure may undergo a second course of treatment.
Results of a large international randomized clinical trial of adjuvant ILP as an adjuvant treatment in individuals with high-risk primary melanoma have been published, however, while the incidence of local recurrence decreased in the treatment group, the overall survival was unchanged. Also, the lack of definitive data either proving or disproving the role of ILP in individuals with surgically resected recurrent satellite lesions or in transit disease provides the rationale of considering this role of ILP as investigational.
SOURCES
Abeloff, M. D., Armitage, J. O., Niederhuber, J. E., Kastan, M. B., & McKenna, W. G. (Eds.). (2004). Clinical Oncology: Isolated limb perfusion (3 rd ed.). Philadelphia: Churchhill Livingstone.
Australian Cancer Network. (2008) Management of locoregionally recurrent melanoma. Retrieved October 27, 2010 from http://www.guideline.gov/content.aspx?id=13461&search=isolated+limb+perfusion.
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2009). Isolated limb perfusion for malignant melanoma (7.01.12). Retrieved October 27, 2010 from BlueWeb. (16 articles and/or guidelines reviewed)
Eggermont, A. M., & ten Hagen, T. L. (2001). Isolated limb perfusion for extremity soft-tissue sarcomas, in-transit metastases, and other unresectable tumors: Credits, debits, and future perspectives. Current Oncology Reports, 3 (4), 359-367.
Grimer, R., Judson, I., Peake, D., & Seddon, B. (2010). Guideline for the management of soft tissue sarcomas. Retrieved October 27, 2010 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903951/?tool=pubmed.
Hayes, A. J., Neuhaus, S. J., Clark, M. A., & Thomas, J. M. (2007). Isolated limb perfusion with melphalan and tumor necrosis factor alpha for advanced melanoma and soft-tissue sarcoma. Annals of Surgical Oncology, 14 (1), 230-238. (Level 2 Evidence - Independent study)
National Cancer Institute. (2008, November). Melanoma treatment (PDQ®). Recurrent melanoma. Retrieved January 15, 2009 from http://www.nci.nih.gov/cancertopics/pdq/treatment/melanoma/HealthProfessional/page11.
National Comprehensive Cancer Network. (2010). Melanoma. Retrieved October 27,2010 from http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf.
National Institute for Health and Clinical Excellence (NICE). (2004, May). Isolated limb perfusion for melanoma. Retrieved October 27, 2010 from http://guidance.nice.org.uk/IP/454.
Sanki, A., Kam, P. C., & Thompson, J. F. (2007). Long-term results of hyperthermic, isolated limb perfusion for melanoma: A reflection of tumor biology. Annals of Surgery, 245 (4), 591-596. (Level 4 Evidence - Independent study)
ORIGINAL EFFECTIVE DATE: 11/1986
MOST RECENT REVIEW DATE: 12/9/2010
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