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Presented February 2007 c/o chronic worsening back pain and was found to have pneumonia. A CT of the chest was performed at that time and showed hepatic abnormalities. Patient reported an abnormality previously reported in his liver 2.5 years earlier.
U/S guided liver biopsy revealed hepatocellular carcinoma with cholangiolar features. Hepatocyte antigen and alpha-fetoprotein immunostains were negative . Serum AFP was 13,156 .
MRI showed extensive involvement of the liver and at least 2 pulmonary nodules with portal vein involvement. Upper and lower endoscopy was negative.
Pathology reviewed at Mayo and thought consistent with HCC but without evidence of cirrhosis .
Repeat biopsy was performed on July 31 st and interpreted as HCC
Enrolled in the avastin/tarceva clinical trial
Course complicated by culture negative fevers and pain
El-Serag, H.B. and K.L. Rudolph, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007. 132 (7): p. 2557-76. Brunetto M.R., O.F., Koehler M., et al., Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study. International Interferon-alpha Hepatocellular Carcinoma Study Group. Lancet, 1998. 351 (9115): p. 1535-9.
Primary staging should be clinical staging, and the CLIP is preferred
Secondary staging with the AJCC - TNM staging system for patients undergoing surgery
Staging work up includes Bone Scan and CT chest
CLIP Score Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000; 31:840 1 >400 2 Massive or extension >50% 1 Multinodular and extension 50% 0 Tumor morphology Uninodular and extension 50% 2 C 1 B 1 Yes 0 Portal Vein Thrombosis No 0 AFP <400 0 Child-Pugh A
Kaplan-Meier estimated survival curves based on the CLIP score (log rank test) Farinati, F, Rinaldi, M, Gianni, S, Naccarato. Cancer 2000; 89:2266.
T2 – solitary tumor with vascular invasion or multiple nodules all <5cm
T3 – multinodular >5cm, or tumor with major vasculature invasion
T4 – Tumor with invasion of adjacent organs
AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, Inc 16% 5 yr survival 37% 5 yr survival 55% 5 yr survival M0 N1 Any T IIIC M0 N0 T4 IIIB M1 Any N Any T Stage IV M0 N0 T3 Stage IIIA M0 N0 T2 Stage II M0 N0 T1 Stage I
Okuda staging system for HCC Adapted from Okuda, K, Ohtuiki, T, Obata, H, et al, Cancer 1985; 56:918. <3 >3 Bilirubin >3 <3 Albumin Abscent Clinically detectable Ascites <50% >50% Tumor size Negative Positive Criteria 0.7 mos survival 2 mos survival 8.3 mos survival 3-4 positive Stage III 1-2 positive Stage II No positive Stage I
Taiwan: HBV immunization of newborns introduced in 1984 resulting in decrease in incidence of HCC
0.7 to 0.36 per 100,000 children
Infant vaccination estimated to prevent 84% of HBV related deaths
94% of deaths occur from cirrhosis and HCC
Chang, M.H., et al., Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med, 1997. 336 (26): p. 1855-9.
Phase III randomised trials of systemic therapy for advanced HCC Yeo et al JNCI 2005; Beaugrand et al J Hepatology 2005, Lai et al. 1988 Cancer Gish et al JCO 2007; Posey et al ASCO 2005; Choi et al. 1984 Cancer Quad Rx: 5FU/Mito/Cy/Vin PIAF: Cisplatin, interferon- 2b, doxorubicin, fluorouracil P=0.14 58% 1 yr OS (n=30) IFNa 38% 1 yr OS (n=28) BSC 58 Llovet et al p=0.85 P=0.0068 p=NS p=0.036 p=0.83 p=0.1 p-value 5.7 mos 5.6 mos 9.6 mos 2.7 mos 8.67 mos 1.6 mos Med survival (n=170) (n=222) (n=60) (n=94) (n=19) T-138067 Nolatrexed Seocalcitol Doxorubicin PIAF* Quad Rx Exp arm 5.6 mos 8.1 mos 9.2 mos 1.9 mos 6.83 mos 3.6 mos Median survival (n=169) (n=223) (n=46) (n=94) (n=45) Doxorubicin Doxorubicin Placebo BSC Doxorubicin Doxorubicin Control arm 339 445 746 106 188 64 Total pts Posey et al Gish et al Beaugrand et al Lai et al Yeo et al Choi et al Authors
Abstract #LBA1: Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial) J. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, J. Raoul, S. Zeuzem, M. Poulin-Costello, M. Moscovici, D. Voliotis, J. Bruix, For the SHARP Investigators Study Group