Hepatobiliary Cancers Clinical Practice Guidelines in OncologyNCCN Categories of Evidence and ConsensusCategory 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus.Category 2A: The recommendation is based on lower-level evidence and there is uniform NCCN consensus.Category 2B: The recommendation is based on lower-level evidence and there is nonuniform NCCN consensus (but no major disagreement).Category 3: The recommendation is based on any level of evidence but reflects major disagreement.All recommendations are category 2A unless otherwise noted.Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.OverviewHepatobiliary cancers are highly lethal. In 2008, approximately 21,370 persons in the United States were estimated to be diagnosed with liver or intrahepatic bile duct cancer and 9520 with gallbladder cancer or other biliary tract cancer. Furthermore, approximately 18,410 deaths from liver or intrahepatic bile duct cancer and 3340 deaths from gallbladder cancer or other biliary tract cancer were estimated to occur.1The types of hepatobiliary cancers covered in these guidelines include hepatocellular carcinoma (HCC), gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. By definition, these guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatments. Although not explicitly stated at every decision point of the guidelines, patient participation in prospective clinical trials is the preferred option for treatment of hepatobiliary cancers.HCCRisk Factors and...
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TakamatsuSNoguchiNKudohA. Influence of risk factors for metabolic syndrome and non-alcoholic fatty liver disease on the progression and prognosis of hepatocellular carcinoma. Hepatogastroenterology2008;55:609–614.
BartlettDLDi BisceglieAMDawsonLA. Cancer of the liver. In: DeVitaVTLawrenceTSRosenbergSA eds. Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2008:1129–1156.
Department of Health and Human Services Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. Available at: www.cdc.gov/nchs/data/nhanes/databriefs/viralhep.pdf. Accessed February 19 2009.
YatsujiSHashimotoETobariM. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol2008;24:248–254.
ChangPEOngWCLuiHFTanCK. Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome. J Gastroenterol2008;43:881–888.
CholongitasEPapatheodoridisGVVangeliM. Systematic review: the model for end-stage liver disease--should it replace Child-Pugh’s classification for assessing prognosis in cirrhosis?Aliment Pharmacol Ther2005;22:1079–1089.
ChevretSTrinchetJCMathieuD. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire. J Hepatol1999;31:133–141.
LeungTWTangAMZeeB. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer2002;94:1760–1769.
KudoMChungHOsakiY. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol2003;38:207–215.
HuoTILinHCHuangYH. The model for end-stage liver disease-based Japan Integrated Scoring system may have a better predictive ability for patients with hepatocellular carcinoma undergoing locoregional therapy. Cancer2006;107:141–148.
NanashimaASumidaYAboT. Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy. J Gastroenterol2006;41:250–256.
WangJHChangchienCSHuTH. The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma—survival analysis of 3892 patients. Eur J Cancer2008;44:1000–1006.
VautheyJNRiberoDAbdallaEK. Outcomes of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. J Am Coll Surg2007;204:1016–1027; discussion 1027–1018.
HuitzilFDCapanuMO’ReillyE. Ranking and improvement of staging systems in advanced hepatocellular carcinoma [abstract]. Presented at the 2008 Gastrointestinal Cancers Symposium; January 25–27, 2008; Orlando, Florida. Abstract 210.
GuglielmiARuzzenenteAPacheraS. Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response. Am J Gastroenterol2008;103:597–604.
PoonRTFanSTLoCM. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg2002;235:373–382.
SeoDDLeeHCJangMK. Preoperative portal vein embolization and surgical resection in patients with hepatocellular carcinoma and small future liver remnant volume: comparison with transarterial chemoembolization. Ann Surg Oncol2007;14:3501–3509.
RiberoDCurleySAImamuraH. Selection for resection of hepatocellular carcinoma and surgical strategy: indications for resection, evaluation of liver function, portal vein embolization, and resection. Ann Surg Oncol2008;15:966–992.
FacciutoMEKoneruBRoccaJP. Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation. Ann Surg Oncol2008;15:1383–1391.
PoonRTFanSTLoCM. Difference in tumor invasiveness in cirrhotic patients with hepatocellular carcinoma fulfilling the Milan criteria treated by resection and transplantation: impact on long-term survival. Ann Surg2007;245:51–58.
DuffyJPVardanianABenjaminE. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg2007;246:502–509; discussion 509–511.
PompiliMMiranteVGRondinaraG. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl2005;11:1117–1126.
LivraghiTMeloniFDi StasiM. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice?Hepatology2008;47:82–89.
ChoiDLimHKRhimH. Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series. Eur Radiol2007;17:684–692.
MaluccioMCoveyAMGandhiR. Comparison of survival rates after bland arterial embolization and ablation versus surgical resection for treating solitary hepatocellular carcinoma up to 7 cm. J Vasc Interv Radiol2005;16:955–961.
LlovetJMRealMIMontanaX. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet2002;359:1734–1739.
DoanPLO’NeilBHMooreDTBernardSA. Predictors of survival in patients with hepatocellular carcinoma treated with transarterial chemoembolization [abstract]. Presented at the 2008 Gastrointestinal Cancers Symposium; January 25–27, 2008; Orlando, Florida. Abstract 204.
YeoWMokTSZeeB. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst2005;97:1532–1538.
RaoulJLSantoroABeaugrandM. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to ECOG performance status: a subanalysis from the SHARP trial [abstract]. J Clin Oncol2008;26(Suppl 1):Abstract 4587.
CraxiAPortaCSangiovanniA. Efficacy and safety of sorafenib in patients with alcohol-related hepatocellular carcinoma: a sub-analysis from the SHARP trial [abstract]. J Clin Oncol2008;26(Suppl 1):Abstract 15591.
BolondiLCasparyJBennounaB. Clinical benefit of sorafenib in hepatitis C patients with hepatocellular carcinoma: subgroup analysis of the SHARP trial [abstract]. Presented at the 2008 Gastrointestinal Cancers Symposium; January 25–27, 2008; Orlando, Florida. Abstract 129.
MillerAAMurryDJOwzarK. Pharmacokinetic and phase I study of sorafenib for solid tumors and hematologic malignancies in patients with hepatic or renal dysfunction: CALGB 60301 [abstract]. J Clin Oncol2007;25(Suppl 1):Abstract 3538.
BartlettDLRamanthanRKBen-JosefE. Cancers of the biliary tree. In: DeVitaVTLawrenceTSRosenbergSA eds. Cancer: Principles & Practice of Oncology. 8th ed: Wolters Kluwer; Lippincott Williams & Wilkins; 2008:1156–1186.
JarnaginWRRuoLLittleSA. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer2003;98:1689–1700.
PawlikTMNathanHAloiaT. A simplified staging system for intrahepatic cholangiocarcinoma [abstract]. Presented at the 2008 Gastrointestinal Cancers Symposium; January 25–27, 2008; Orlando, Florida. Abstract 194.
TakadaTAmanoHYasudaH. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer2002;95:1685–1695.
ShinoharaETMitraNGuoMMetzJM. Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys2008;72:1495–1501.
BorgheroYCraneCHSzklarukJ. Extrahepatic bile duct adenocarcinoma: patients at high-risk for local recurrence treated with surgery and adjuvant chemoradiation have an equivalent overall survival to patients with standard-risk treated with surgery alone. Ann Surg Oncol2008;15:3147–3156.
LimKOhEChieE. Which is better in patients with curatively resected extrahepatic biliary tract cancer? Adjuvant concurrent chemoradiation alone versus CCRT followed by maintenance chemotherapy [abstract]. J Clin Oncol2008;26(Suppl 1):Abstract 15659.
LinLLPicusJDrebinJA. A phase II study of alternating cycles of split course radiation therapy and gemcitabine chemotherapy for inoperable pancreatic or biliary tract carcinoma. Am J Clin Oncol2005;28:234–241.
RaoSCunninghamDHawkinsRE. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer. Br J Cancer2005;92:1650–1654.
KoeberleDSalettiPBornerM. Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter, phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol2008;26:3702–3708.
NehlsOOettleHHartmannJT. Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer2008;98:309–315.
KobayashiKTsujiAMoritaS. A phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and low-dose consecutive (Cisplatin) in advanced biliary tract carcinoma. BMC Cancer2006;6:121.
AlbertsSRAl-KhatibHMahoneyMR. Gemcitabine, 5-fluorouracil. And leucovorin in advanced biliary tract and gallbladder carcinoma. A North Central Cancer Treatment Group phase II trial. Cancer2005;103:111–118.