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Regional cancer therapies are treatments that direct a therapeutic intervention to a cancer burdened organ or region of the body; they have the collective advantage of intensifying a treatment to a site of known disease while avoiding unnecessary systemic toxicity. They are most beneficial in circumstances where the tumor biology is favorable; that is, the site of regional metastatic spread is recognized to be the sole or life-limiting component of the patient's disease. Two general categories of regional therapy include vascular infusion or perfusion and local ablation. Vascular isolation and perfusion of a cancer-bearing organ or region of the body using a recirculating extracorporeal perfusion circuit has been in clinical use for almost 50 years. Isolation perfusion was initially applied under normothermic conditions with chemotherapeutics alone and subsequently mild-to-moderate hyperthermia (38.5°C to 42°C) became a routine component of treatment when it was shown to be associated with improved response rates.1 In the early 1990s there was renewed interest in isolation. Most recently, there has been interest in the development of percutaneous techniques of isolated limb or liver infusion. The use of local ablative therapies such as radiofrequency ablation or irreversible electroporation has become increasingly utilized as a strategy to obliterate limited sites of disease in liver or other tissues. This chapter reviews the principles and techniques of isolation perfusion and infusion as well as the current status of these modalities in clinical practice. The various components of therapy that are routinely used are also reviewed.
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Technique of Isolation Perfusion
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There are advantages to isolation perfusion as a treatment technique in appropriately selected patients. Complete separation of the regional and systemic circulation can be achieved in most circumstances which allow for dose intensification of therapeutics to the cancer-burdened organ or region. The main parameter that limits dose escalation is the tolerance of the normal tissues within the perfusion field. In some circumstances, agents that cannot be administered systemically can be given via isolation perfusion. For example, tumor necrosis factor (TNF) is a biological agent that was demonstrated to have potent anti-tumor activity in murine models but had severe dose-limiting systemic toxicity in clinical trials when administered intravenously at doses far below the therapeutic threshold.2,3 However, when perfusate leak is controlled, TNF can be administered at doses that are manyfold higher than those tolerated systemically. It has been used in isolated limb, liver, lung, or kidney perfusion and is currently approved for use in Europe with melphalan administered via isolated limb perfusion (ILP) for patients with advanced extremity melanoma or sarcoma.4,5 There are data from experimental models demonstrating the feasibility of using isolation perfusion to selectively administer agents such as antisense oligonucleotides or recombinant mutant vaccinia virus within the perfusion field.6,7
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Isolation perfusion is a surgical procedure performed under a general anesthetic with perfusion duration of 60 minutes for liver and 90 ...