© Springer International Publishing Switzerland 2015
Leonard Berliner and Heinz U. Lemke (eds.)An Information Technology Framework for Predictive, Preventive and Personalised MedicineAdvances in Predictive, Preventive and Personalised Medicine810.1007/978-3-319-12166-6_1010. Minimally Invasive Therapies for Hepatocellular Cancer: Catheter-Directed Therapies
(1)
New York Methodist Hospital, Brooklyn, NY, USA
(2)
Weill Medical College of Cornell University, New York, NY, USA
Abstract
Techniques have been developed for catheter-directed delivery of therapy for hepatocellular carcinoma (HCC) since the 1980s, and are still undergoing evolution. Currently, this involves embolization with particles, as well as delivery of chemotherapeutic agents with a variety of materials, and is referred to as transarterial chemoembolization (TACE). TACE is made both feasible and effective due to the dual blood supply of the liver. Advances in catheter and guide wire technology have been accompanied by the development of techniques for the superselective placement of catheters for the safe and effective delivery of therapeutic agents to hepatic tumors. TACE is recommended for patients with Intermediate Stage, multi-nodular HCC (Okuda Stage 1–2; Childs-Pugh Stage A-B; Performance Status 0). Combination therapy with RFA and TACE may lead to more extensive tumor necrosis than mono-ablative therapy and may be a more effective treatment for HCC. Further study will be needed to determine the effectiveness of combining RFA and TACE, and in which order. The combination of TACE with antiangiogenic agents, such as sorafenib, is under investigation as well. The use of sorafenib may curtail the post-TACE rise in VEGF-mediated signaling, and simultaneously target tumor foci distant from the site of treatment. Selection parameters and treatment outcomes for locoregional therapies, alone or in combination, such as thermal ablation and TACE, with or without systemic chemotherapy agents will eventually be factored in generating Digital Patient Models (DPMs) to facilitate diagnosis, prognosis, and treatment selection, i.e. Model Guided Therapy (MGT) and Predictive, Preventive and Personalized Medicine (PPPM).
Keywords
Personalized medicineHepatocellular carcinomaLocoregional therapyTreatmentTransarterial chemoembolization (TACE)Drug-eluting beadsSorafenib10.1 Introduction
Techniques have been developed for catheter-directed delivery of therapy for hepatocellular carcinoma (HCC) since the 1980s, and are still undergoing evolution [1–4]. This has included bland embolization with particles, as well as delivery of chemotherapeutic agents, with a variety of materials, referred to as transarterial chemoembolization (TACE). (Radioembolization with Yttrium-90 microspheres is discussed in Chap. 11.)
10.1.1 Transarterial Chemoembolization for Hepatocellular Carcinoma
TACE is made both feasible and effective due to the dual blood supply of the liver. HCC derives 95 % of its blood supply from the hepatic artery, whereas normal hepatic parenchyma is supplied 75 and 25 % by the portal vein and hepatic artery, respectively. (These differences in arterial supply account for the detectability of early HCC on dynamic, contrast-enhanced computed tomography [CT] and magnetic resonance imaging [MRI] as described in Chaps. 3 and 4). Advances in catheter and guide wire technology have been accompanied by the development of techniques for the superselective placement of catheters for the safe and effective delivery of therapeutic agents to hepatic tumors.
As indicated by the Barcelona Clinic Liver Cancer (BCLC) Staging Classification and Treatment Schedule [5, 6] TACE is recommended in patients with Intermediate Stage (Okuda Stage 1–2; Childs-Pugh Stage A–B; Performance Status 0) with multi-nodular HCC. Relative contraindications to TACE, which are evolving as increasing experience is gained, have included: greater than 50 % liver involvement (although patients may be consider for staged procedures); LDH > 425; AST > 100; total bilirubin > 2; biliary obstruction; stent; anastomosis; and portal vein invasion or occlusion. Childs-Pugh Class B and C cirrhotic patients, as well as patients with end stage HCC, are at an increased risk of liver failure and death and are not appropriate candidates for TACE [3].
Two different basic methodologies have developed over the years for the transcatheter delivery of chemotherapy to hepatocellular carcinoma.
10.1.1.1 Iodized Poppy Seed Oil
The first method utilizes iodized poppy seed oil, which is injected into the hepatic artery, and remains preferentially localized within the neovascularity of HCC. The oily substance serves as a vehicle for the delivery of cytotoxic agents to tumor sites in the liver. Cytotoxic agents which have been used include doxorubicin (Adriamycin), 5-fluorouracil, cisplatin, and mitomycin. The poppy seed oil, combined with embolic particles, causes ischemia and prolonged contact of the chemotherapeutic agent with the tumor. The dose of doxorubicin typically ranges from 30 to 75/m2, to a maximum of 150 mg, which is usually mixed with 5 to 20 mL of lipiodol [7].
10.1.1.2 Drug-Eluting Beads
The second method for transcatheter delivery of chemotherapy to HCC utilizes drug-eluting beads or particles (DEB-TACE) to carry and deliver the chemotherapeutic agent. At the time of this writing, particles in use include 100–300 μm alcohol-sodium acrylate microspheres (QuadraSphere microspheres) and polyvinyl alcohol (PVA) hydrogel that has been modified with sulphonate groups (DC Beads). For patients with single tumor < 5 cm, or multiple tumors (up to three, < 3 cm each), each single treatment should include a planned dose of 50 to 75 mg doxorubicin loaded into one vial containing 2 mL of DC Beads (loading dose, 25 to 37.5 mg doxorubicin/mL of beads). For patients with more advanced disease each single treatment should include a planned dose of up to 150 mg doxorubicin loaded into two vials of DC Beads. In huge or bilobar tumors, treatment typically includes separate sessions approximately 4 weeks apart, in the absence of complications that would require a longer time interval between the two sessions. Obtaining confirmation that the liver enzymes have returned to baseline before performing the second treatment session is recommended [7].
The beads are allowed to remain in a container with the chemotherapeutic agent prior to administration, to allow the agent to be absorbed by the beads. After catheter delivery, the particles remain lodged in the injected hepatic arterial branches, so that the cytotoxic agent is eluted over a prolonged period of time (7–10 days) to tumor sites in the liver. As stated above, at the current time, the cytoxic agent most commonly employed is doxorubicin (Adriamycin). The drug-eluting particles produce tumor ischemia and prolonged contact of the chemotherapeutic agent with the tumor.
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