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clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
肝癌年報
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Hepatocellular Carcinoma: Overview
Burden of HCC
Surveillance and diagnosis
Staging and treatment algorithms
– Early HCC
– Intermediate HCC
– Advanced HCC
A look to the future
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
衛生署 2008 & 2010 死亡統計
惡性腫瘤自 1982 年起即高居台灣民眾死因首位,
2008 年死亡人數首次破 14 萬人,標準化死亡率為每 10 萬人口 484.3 人
十大死因:惡性腫瘤為 3萬 8913 人,佔所有死亡人數的 27.3% 、標準化死亡率為每 10 萬人口 133.7 人
2008 年十大癌症順位分別是肺癌占 20% 、肝癌占 19.7% 、結腸直腸癌占 11%、女性乳癌占 4% 、胃癌占 5.9%
衛生署資料顯示, 2010 年死亡人數占率依序為:惡性腫瘤占 28.4% 、心臟疾病占 10.8% 、腦血管疾病占 7.0% 、
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
肝細胞癌 的發生率
在民國 69 年的統計中,男性與女性的每十萬人死亡率分別是 26.10 及 8.14
肝細胞癌 的發生率男性是每十萬人有二十五人,在女性是每十萬人有十人。
年發生率在慢性 B 型肝炎的人是 0.826 %,在大於 35 歲的慢性 B 型肝炎病人是 2.77 %,在肝硬化的人是 5.6 %,
在 B 型肝炎病毒表面抗原 (HBsAg) 陰性的肝硬化病人是4.5-6.2 %,在 HBsAg 陽性的肝硬化病人是 5.7-7.7 %。
台灣的肝癌死亡率在東部山區有顯著的較高,而在西部山區則較低。最高的死亡率見於澎湖群島
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
肝癌最盛行的年齡 肝癌最盛行的年齡見於 31至 60 歲之間,在民國 50 年代,
最高的發生率是在 41 至 50 歲之間,但在爾後的研究則為50至 60 歲。
肝硬化併發肝癌的平均年齡是 56.7 歲,在非肝硬化者則為52 歲。 HBsAg 陽性的肝癌病人,其平均年齡是 55 歲,而在 HBsAg 陰性且 C 型肝炎病毒抗體陽性的肝癌病人 , 其平均年齡是 65.7 歲。
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Malignant TransformationMultistep
Potential Targets
Oxidative stress and
inflammation
Viral oncogenes
Carcinogens
Growth factors Telomere shortening
Cancer stem cells
Loss of cell cycle checkpoints
Antiapoptosis
Angiogenesis
Normal liver
Liver cirrhosis
Hepatitis CHepatitis B
EthanolNASH
Epigenetic alterationsGenetic alterations
HCC[2]
Dysplastic nodules[1]
1. Tornillo L, et al. Lab Invest. 2002;82:547-553. 2. Verslype C, et al. AASLD 2007. Abstract 24.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Surveillance for Hepatoma
Cost-effective
The expected HCC > 1.5% /year in patients with hepatitis C and 0.2% / year in patients with hepatitis B
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Patients for Whom HCC Surveillance Is Recommended Asian males HBV carriers older than 40 yrs of age
Asian female HBV carriers older than 50 yrs of age
HBV carrier with HCC family history
African/N American blacks with HBV
Cirrhotic HBV carriers
Hepatitis C with cirrhosis
Stage 4 primary biliary cirrhosis
Genetic hemochromatosis and cirrhosis
Alpha-1 antitrypsin deficiency and cirrhosis
Other cirrhosis
80% of patients with HCC have underlying cirrhosis
Bruix J, et al. AASLD HCC guidelines. July 2010. Simonetti RS, et al. Dig Dis Sci. 1991;36:962-972.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
AASLD Surveillance Guidelines
Surveillance recommended in at-risk groups
– Specific hepatitis B carriers
– Non–hepatitis B cirrhosis
HCC surveillance should be performed with ultrasound
Patients should be screened at 6-mo intervals
– Increased surveillance interval in patients at higher risk not needed
Bruix J, et al. AASLD HCC guidelines. July 2010.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Diagnosis of HCC should be based on imaging techniques and/or biopsy
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Diagnostic Algorithm for Suspected HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Diagnosis of Hepatocellular Carcinoma
The application of dynamic imaging criteria applied only to patients with
cirrhosis of any etiology
chronic hepatitis B who may not have fully developed cirrhosis or have regressed cirrhosis.
High-grade dysplastic nodules or HCC ?? staining for
1.glypican 3
2.heat shock protein 70
3 glutamine synthetase
Positivity for two of these three stains confirms HCC
Bosetti C, Levi F, Boffetta P, Hepatology 2008;48:137–145.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Staging Systems and Treatment Strategies in HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Variables used in staging
Tumor factors
- Tumor size
- Portal vein thrombosis
- AFP
Liver function
- Child - Pugh criteria
- MELD - score
Over all heath of the patient
Performance status
Efficacy of treatment
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Staging systems for Hepatoma Clinical staging vs Pathological staging
Outcome prediction
- TNM - Okuda
- CLIP
(The Cancer of the Liver Italian Program)
- JIS ( Japanese Integrated score )
Treatment option
- BCLC ( Bacelona Clinic Liver Cancer)
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
AJCC staging system 2002
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
The prognostic value of the AJCC staging system (the 2002 edition)
Has been validated in liver transplantation
The most accurate system to stratify post-transplantation outcomes
The AJCC staging is the only one that is validated in patients treated with either hepatic resection or transplantation
Vauthey JN, Ribero D, Abdalla EK, J Am Coll Surg. 2007;204(5):1016.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
The prognostic value of the AJCC staging system (the 2002 edition)
Five-year survival rates, based upon the TNM staging system are as follows
Stage I – 55 percent
Stage II – 37 percent
Stage III – 16 percent
Vauthey JN, Lauwers GY, Esnaola NF, J Clin Oncol. 2002;20(6):1527.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Tumor, Node, Metastasis (TNM) staging
Staging of liver cancer includes only HCC; intrahepatic bile duct cancer is staged separately.
The T3 category is split any of which are >5 cm (T3a; stage IIIA) versus tumors of any size that involve a major portal vein or hepatic vein (T3b, stage IIIB).
stage IIIC disease. A T4 primary (direct invasion of an adjacent organ other than the gallbladder or with perforation of the visceral peritoneum) constitutes
Inferior phrenic lymph nodes are no longer classified as a distant metastatic site (stage IVB) but as regional lymph node involvement (N+, stage IVA).
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Tumor, Node, Metastasis (TNM) staging
Stage IV include all metastasis
Stage IVa - includes node-positive disease (N1).
Stage IVb- distant metastasis (M1).
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
TNM-7- 2010Classification for Hepatocellular Carcinoma
TNM-7 Classification for Hepatocellular Carcinoma 2010
T N M
Stage T1 Single, no vascular Invasion 0 0
Stage T2 Single with vascular invasion, or Multiple tumors non> 5cm
0 0
Stage T3a Multiple tumor with any > 5cm 0 0
Stage T3b Any T with major portal vein or hepatic vein
0 0
Stage T3c T4 adjacent organ, No GB ,No perforation of visceral peritoneum
0 0
Stage IVa Any T N1 0
Stage IVb Any T Any N 1
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Okuda staging System
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
The Cancer of the Liver Italian Program score (CLIP)
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
CLIP in Clinical Practice
THE CANCER OF THE LIVER ITALIAN PROGRAM (CLIP) INVESTIGATORS HEPATOLOGY 1998; 28:751-755.
HEPATOLOGY 2000;31: 840-845.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
The French Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH)
Multivariate analysis of prognostic factors in 761 patients from 34 countries
Five prognostic factors :
Karnofsky performance status
Serum bilirubin >50 micromol/L (>2.9 mg/dL)
Serum alkaline phosphatase at least twice the upper ≧limit of normal
Serum alpha-fetoprotein >35 ng/mL
Ultrasonographic portal obstruction
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
JIS (Japanese Integrated Score)
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
BCLC Staging System
Terminalstage (D)
Okuda 1-2, PS 0-2, Child-Pugh A-B
Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0
Intermediate stage (B)
Okuda 3, PS > 2,Child-Pugh C
Very early stage (0)Single < 2 cmCarcinoma in situ
Early stage (A)Single or 3 nodules
Advanced stage (C)Portal invasion,
PS 0, Child-Pugh A
HCC
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
Stage 0 Stage A-C Stage D
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Marrero JA, et al. Hepatology. 2005;41:707-716.
Variables Used in HCC Staging Systems
System Tumor Staging Liver Function Health Status
Europe-US
GETCH/
French
PVT; AFP < 35 or > 35 ug/L Bilirubin, alkaline phosphatase
Karnofsky
CLIP Number of nodules, tumor > or < 50% area of liver, and PVT;
AFP< 400 or ≥ 400 ng/mL
CTP No
BCLC Tumor size, number of nodules, and PVT
CTP PST
TNM Number of nodules, tumor size, presence of PVT, and presence of metastasis
No No
Asia
JIS TNM CTP No
Okuda/
Tokyo
Tumor > or < 50% of cross-sectional area of liver
Ascites, albumin, and bilirubin
No
CUPI TNM; AFP< 500 or ≥ 500 ng/mL Bilirubin, ascites, alkaline phosphatase
Symptoms
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Comparison of HCC Staging Systems
BCLC system uses key independent predictors of survival
– Performance score, portal vein thrombosis, tumor diameter
Compared with other staging systems in cohort study
– BCLC had best stratification of survival across all stages
– BCLC was only system to have independent predictive value on survival
BCLC is the only staging system that stratifies patients into treatment groups
Marrero JA, et al. Hepatology. 2005;41:707-716.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Liver transplantation RFA/PEI
Curative treatments (30%); 5-yr survival: 40%-70%
TACE
Single
Increased Associateddiseases
Normal No Yes
Sorafenib
Portal pressure/bilirubin
3 nodules ≤ 3 cm
Resection Symptomatic (20%); survival
< 3 mosRCTs (50%); 3-yr survival: 10%-40%
Terminalstage (D)
Okuda 1-2, PS 0-2, Child-Pugh A-B
Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0
Intermediate stage (B)
Okuda 3, PS > 2,Child-Pugh C
Very early stage (0)Single < 2 cmCarcinoma in situ
Early stage (A)Single or 3 nodules
Advanced stage (C)Portal invasion,
PS 0, Child-Pugh A
HCC
BCLC Staging and Treatment Strategy
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Treatment for Very Early Stage Hepatoma
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Treatment for Very Early Stage Hepatoma
Hepatic resection or ablation of HCC lesion < 2cm have the same 5- year survival rates
Decision based on tumor location, hepatic function, functional status, other co-morbidities, local practice
Resection limited to patients with compensated cirrhosis
- bilirubiin < 2mg/dl, No portal hypertension, platelet >105
In studies of Child A resection for tumor <2 cm -
The 5 year survival rates 49-93%, 5 year recurrence 80%
1. Takayama T, Hepatology 1998;28:1241–1246. 2. Ikai I Cancer 2004;101:796– 802 3. Zhou XD Cancer 2001;91:1479–1486. 4. Nathan H Ann Surg 2009; 249:799–805.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Ablation as the first lineapproach for very early HCC
A cohort study of radiofrequency ablation of 218 patients
Complete ablation of lesions < 2 cm - 97% in 31 ms, with a local recurrence rate of less than 1%.
5 year recurrence rate 80%
NO RCT to compare surgery or RFA
Markov Model simulating 10,000 patients -overall survival was nearly identical in RFA and HR
Livraghi T, Meloni F, Di Stasi M, et al. HEPATOLOGY 2008;47:82-89.
Cho YK, Kim JK, Kim WT, et al. Hepatology 2010;51:1284–1290.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Treatment for Early Stage Hepatomas
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Resection Option
Portal pressure measurement to predict the outcome has been validated in Japan.
First option for patients who have the optimal profile, as defined by the BCLC staging system.
Advanced liver disease, the mortality is higher – liver transplantation or ablation.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Resection versus Ablation
A RCT comparing Child-Pugh class A cirrhosis who have single HCCs 5 cm or less in diameter
- No statistically significant differences
Nonrandomized investigations –
RFA can achieve similar survival rates as surgical resection in small, solitary tumors at the very early stage of the BCLC classification
The response rates to RFA 70-95% in tumor < 3cm,
In tumors 3 cm response rates 50-70% in > 3 cm. ≧overall 5 year survival 30 - 50 %
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Candidates for RFA/PEI
Includes individuals who are not candidates for surgery
Radiofrequency ablation generally preferred over percutaneous ethanol injection
– Necrotic effect more predictable across tumor sizes
– Meta-analyses suggest survival benefit with radiofrequency ablation vs percutaneous ethanol injection
Bruix J, et al. AASLD HCC guidelines. July 2010.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Combining RF ablation with TACE for (3.1–5.0 cm) HCCs
An RCT - evaluating the therapeutic efficacy of Combining RF ablation with TACE
Local tumor progression rate were significantly lower in the TACE and RF ablation–treated group than in the RF ablation–only group (6% vs 39%, P =0.012)
A phase III randomized double-blinded placebo controlled study with thermally sensitive liposomal doxorubicin in combination with RF ablation HCC is ongoing.
Morimoto M , Numata K , Kondou M Cancer 2010 ; 116 ( 23 ): 5452 – 5460 .
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Adjuvant Therapy in the Resection Setting
Recurrence following resection
(in one year –metastasis , late recurrence -De no Vo carcinogenesis)
– Approximately 50% at 3 yrs
– Approximately 70% at 5 yrs
Positive results for several types of adjuvant therapy in this setting
– However, no standard-of-care adjuvant therapy for HCC patients undergoing resection
– RCT using Vit K2 , 548 patients- not effective
Sorafenib after resection or ablation - ongoing
Large, randomized, controlled trials of adjuvant therapy following resection
Llovet JM, et al. Hepatology. 1999;30:1434-1440.Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Liver Transplantation for HCC:Milan Criteria (Stage 1 and 2)
5-yr survival with transplantation: ~ 70%
5-yr recurrent rates: < 15%
+Absence of macroscopic vascular invasion,
absence of extrahepatic spread
Single tumor, not > 5 cm Up to 3 tumors, none > 3 cm
Mazzaferro V, et al. N Engl J Med. 1996;334:693-699.Llovet JM. J Gastroenterol Hepatol. 2002;17(suppl 3):S428-S433.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
UCSF (University of California, San Francisco criteria)
Solitary tumor < or = 6.5 cm,
Three or fewer nodules with the largest lesion < or = 4.5 cm
Total tumor diameter < or = 8 cm, without gross vascular invasion
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Solitary large ( > 5-cm) tumor
Not early-stage disease because they do not qualify for transplantation
No upper limit of size for surgical resection appears in the BCLC flowchart
These patients should not be excluded from surgical referral because their tumors are too large
The results of transarterial therapies as standalone treatments are highly variable
Down staging?
Majno PE , Mentha G , Mazzaferro V ..Hepatology 2010 ; 51 ( 4 ): 1116 – 1118 .
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Treatment of Intermediate HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Liver transplantation RFA/PEI
Curative treatments (30%); 5-yr survival: 40%-70%
TACE
Single
Increased Associateddiseases
Normal No Yes
Sorafenib
Portal pressure/bilirubin
3 nodules ≤ 3 cm
Resection Symptomatic (20%); survival
< 3 mosRCTs (50%); 3-yr survival: 10%-40%
Terminalstage (D)
Okuda 1-2, PS 0-2, Child-Pugh A-B
Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0
Intermediate stage (B)
Okuda 3, PS > 2,Child-Pugh C
Very early stage (0)Single < 2 cmCarcinoma in situ
Early stage (A)Single or 3 nodules
Advanced stage (C)Portal invasion,
PS 0, Child-Pugh A
HCC
Unresectable HCC
BCLC Staging and Treatment Strategy
Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Llovet JM, et al. Hepatology. 1999;29:62-67.
Natural History of Nonsurgical HCCStudy Design: Control Arm of 2 RCTs
102 untreated cirrhotic patients with unresectable HCC
– Managed with symptomatic treatment
Median survival of 17 months (range: 1-60 months)
– 1-yr survival was 54%
– 2-yr survival was 40%
– 3-yr survival was 28%
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Llovet JM, et al. Hepatology. 2003;37:429-442.
Arterial Embolization for HCCMeta-analysis of 6 RCTs (2-Yr Survival)
Random Effects Model,OR (95% CI)
Author, Journal Yr Patients, n
Lin, Gastroenterology 1988 63
GETCH, NEJM 1995 96
Bruix, Hepatology 1998 80
Pelletier, J Hepatol 1998 73
Lo, Hepatology 2002 79
Llovet, Lancet 2002 112
Overall 503
Median survival: ~ 20 mos
0.01 0.1 0.5 1 2 10 100
Z = -2.3P = .017
Favors Treatment Favors Control
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Contraindications to TACE
Extrahepatic tumor spread
Lack of portal blood flow
– Portal vein thrombosis, portosystemic anastomoses or hepatofugal flow
Advanced liver disease (Child-Pugh Class B or C)
Clinical symptoms of end-stage cancer
Bruix J, et al. AASLD HCC guidelines. July 2010.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Survival After Yttrium-90 Resin MicrosphereRadioembolization of HCC
325 patients September 2003 and December 2009
Child-Pugh class A (82.5%), underlying cirrhosis (78.5%)
Common adverse events were: fatigue, nausea/vomiting, and abdominal pain.
Grade 3 or higher increases in bilirubin were reported in 5.8% of patients.
All-cause mortality was 0.6% and 6.8% at 30 and 90 days
Bruno Sangro, Livio Carpanese, Roberto CianniHEPATOLOGY 2011;54:868-878)
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Survival After Yttrium-90 Resin MicrosphereRadioembolization of HCC The median overall survival was 12.8 months (10.9-15.7 months)
BCLC A, 24.4 months [18.6-38.1 months]
BCLC B, 16.9 months [12.8-22.8 months]
BCLC C, 10.0 months [7.7-10.9 months
Bruno Sangro, Livio Carpanese, Roberto Cianni HEPATOLOGY 2011;54:868-878
Overall median survival was 7.3 months in patients with BCLC class C without extrahepatic metastases and
10.4 months (95% CI: 7.2, 16.6) in those with Child-Pugh A with portal vein thrombosis
Salem R , Lewandowski RJ , Mulcahy MF , et al . Gastroenterology 2010 ; 138 ( 1 ): 52 – 64 .
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Treatment of Advanced HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Understanding Survival Outcomes in HCC Patients
HCC
Stage 0PS 0, Child-Pugh A
Stage DOkuda 3, PS > 2, Child-Pugh C
Stage A-COkuda 1-2, PS 0-2, Child-Pugh A-B
Very early stage (0)
Single < 2 cmCarcinoma in situ
Early stage (A)Single or 3 nodules
< 3 cm, PS 0
Intermediate stage (B)
Multinodular, PS 0
Advanced stage (C)Portal invasion, N1, M1, PS 1-2
Terminalstage (D)
2010
2012 60% 20% 20%
Median OS > 36 mos Median OS 16 mos
Median OS 6 mos (4-8 mos)
Curative therapiesOS > 60 mos
Sorafenib: 10.7 mosTACE:
OS 20 mos
40% 20% 40%
Natural History
With Therapy
2011 Stage at Diagnosis
Courtesy of Josep M. Llovet, MD.
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Llovet JM, et al. N Engl J Med. 2008;359:378-390.
Patients with advanced,
measurable HCC,
ECOG PS 0-2
(N = 602)
Sorafenib 400 mg BID PO(n = 299)
Placebo(n = 303)
Stratification by macroscopic vascular invasion and/or
extrahepatic spread, ECOG PS, geographical region
Primary endpoints: OS, time to symptomatic progressionSecondary endpoints: progression (radiologic, clinical), adverse events
Phase III SHARP Trial: Sorafenib vs Placebo in Advanced HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Llovet JM, et al. N Engl J Med. 2008;359:378-390. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
Phase III SHARP Trial: OS (ITT)
Sorafenib (n = 299)Median: 10.7 mos (95% CI: 9.4-13.3)
Placebo (n = 303)Median: 7.9 mos (95% CI: 6.8-9.1)
1.00
0.75
0.50
0.25
0
Su
rviv
al P
rob
abili
ty
HR (S/P): 0.69 (95% CI: 0.55-0.88;P = .00058)
0 808 16 24 32 40 48 56 64 72WksPts at Risk, n
SorafenibPlacebo
299303
274276
241224
205179
161126
10878
6747
3825
127
02
00
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
Llovet JM, et al. N Engl J Med. 2008;359:378-390. Cheng AL Lancet Oncology 2009; 10: 25-34
Conclusions From Phase III SHARP Trial
Sorafenib is first systemic therapy to prolong survival in HCC patients
– Survival: HR: 0.69; 31% decrease in risk of death
– Time to radiologic progression: 5.5 mos with sorafenib vs 2.8 mos with placebo (P < .001)
– In Asian patients , an identical RCT shows a median survival time of 4.2 months ( placeb) vs 6.5 months
Sorafenib is the new reference standard for systemic therapy of HCC patients
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
HCC Management
HCC is the intersection of 2 diseases
– Liver disease and cancer
Skilled pathologists needed for diagnosis
Specialists required to deliver treatment options
– Surgeons for resection or transplantation
– Radiologists ( Hepatologist )for ablation and chemoembolization
Hepatologists and oncologists follow treatment strategy and labs
Midlevel providers bring support, particularly for oral therapy
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
性別分佈 M: F = 2 : 1
─【肝癌 性別分佈圖】
, 80男生, 101男生
, 121男生
, 27女生
, 43女生
, 56女生
020406080
100120140160180200
2008 2009 2010 年份
人數
女生男生
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
年齡分佈 50- 79
─【肝癌 年齡層分佈圖】
0
10
20
30
40
50
60
00~19 20~29 30~39 40~49 50~59 60~69 70~79 80以上年齡層
人數
2008
2009
2010
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
臨床期別分佈 - stage I,II, III 增加
─【肝癌 臨床期別分佈】
0
10
20
30
40
50
60
Ⅰ 期 Ⅱ 期 Ⅲ A期 Ⅲ B期 Ⅲ C期 Ⅳ期 不詳 期別
人數
2008
2009
2010
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
首次治療方式分佈 ─臨床期別Ⅰ期 - 開刀與局部治療增加
(C220)I【肝癌 期治療方式分佈圖】
74 5 6
38
16
11
0
14
18 20
4 3 30
5
10
15
20
25
²手術 ³局部治療 栓塞 化療 放療 其他 治療方式
人次
2008
2009
2010
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
AJCC 臨床期別
─ AJCC【肝癌 臨床分期】
020406080
100120140160180
AJCC(Ⅰ ~Ⅳ )期
AJCC不適用
AJCC 不詳 期別
申報數
2008
2009
2010
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
期別相關分佈
AJCC 臨床及病理期別為不詳比例年份 申報數 AJCC 臨床
與病理期別皆填寫不詳之 申報數
%
2008 107 10 9.35
2009 144 0 0
2010 177 0 0
─ AJCC【肝癌 臨床及病理期別為不詳比例】
0.00
2.00
4.00
6.00
8.00
10.00
1 年份
百分比
2008
2009
2010
2008 20102009
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
本院肝癌病患存活率分析結果 ─治療方式 OP與 RFA
●利用生命表法來繪製 OP與 RFA 療法之存活曲線 (N =120)
註 1 :以 生命表法分析。
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC
clinicaloptions.com/oncology
A Multidisciplinary Perspective on the Management of HCC