Hepatocellular Carcinoma

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     1  Hepatocellular Carcinoma What are the treatment options for our patient?
     2  Our Patient 79yo female with multiple co-morbidities, including vascular dementia and AAA Underlying cirrhosis of unknown etiology Hepatoma recognized incidentally on abdominal and chest CT performed for other reasons One lesion – 3.5 x 3.5 cm Liver disease + characteristic radiographic appearance + elevated AFP = diagnosis Child-Pugh – Class A
     3  HCC – Background Variable incidence worldwide Major etiologic associations: cirrhosis, HBV, HCV, EtOH, aflatoxins, HH Various pathologic manifestations Clinical presentation non-specific, masked by underlying disease Dx: clinical picture, imaging (US for screening, helical CT for vascular involvement), AFP; acute decompensation and/or rising AFP in setting of known liver disease Course: early mortality; metastases to lungs 1st; death from cachexia, GI/variceal bleeding, hepatic coma, rarely tumor rupture with hemorrhage
     4  HCC – Staging Staging and prognosis difficult due to presence of two diseases: cancer and cirrhosis Stage of tumor, severity of underlying liver disease Numerous proposed systems AJCC TNM, Okuda, CLIP Barcelona Clinic Liver Cancer (BCLC) staging
     5  HCC – Non-surgical Treatment Radiofrequency Ablation Modifies temperature of neoplastic cells via single or multiple electrodes Percutaneous, laparoscopically, or during laparotomy Most extensively used alternative to PEI Superior long-term survival and recurrence rates compared to chemical ablation Survival rates comparable to resection – potential alternative to surgery?
     6  HCC – Non-surgical Treatment Transarterial Chemoembolization (TACE) Arterial embolization = most common primary treatment for unresectable HCC Obstruction of hepatic artery leads to necrosis of highly vascularized HCC Gelatin may be mixed with chemotherapeutic agents, adding local chemotherapy effect Modest survival benefit over conservative management
     7  HCC – Non-surgical Treatment Sorafenib Oral multikinase inhibitor Blocks tumor cell proliferation via effect on Raf/MEK/ERK signalling (enhances tumor growth and survival), exerts antiangiogenic effect via effect on VEGFRs and PDGFR-ß tyrosine kinases September 2006 Phase II study – demonstrated antitumor activity in advanced HCC; comparable survival and stable disease rates to trials of combination chemotherapy June 2007 – 44% improvement in overall survival versus placebo (median OS 10.7 v. 7.9 months) Toxicity –diarrhea (11%), fatigue (10%), hand-foot skin reaction (8%), bleeding (6%)
     8  Sources Abou-Alfa, Ghassan K., et al. “Phase II Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma.” Journal of Clinical Oncology 24 (26): 4293-4298. Galandi, D. and Antes, G. “Radiofrequency thermal ablation versus other interventions for hepatocellular carcinoma.” The Cochrane Database of Systematic Reviews 1 (2008). Garrean, Sean, et al. “Radiofrequency ablation of primary and metastatic liver tumors: a critical review of the literature.” The American Journal of Surgery 195 (2008): 508-520. Llovet, J., et al. Abstract No: LBA1. Journal of Clinical Oncology 25 (18S). Llovet, Josep M. “Updated treatment approach to hepatocellular carcinoma.” Journal of Gastroenterology 40 (2005): 225-235. Ribero, Dario, et al. “Selection for Resection of Hepatocellular Carcinoma and Surgical Strategy: Indications for Resection, Evaluation of Liver Function, Portal Vein Embolization, and Resection.” Annals of Surgical Oncology. Published online 31 January 2008. Accessed 6 June 2008. UpToDate articles addressing the diagnosis, etiology, and treatment of Hepatocellular Carcinoma.