hepatobiliary

Continue NCCN Clinical Practice Guidelines in Oncology™ Hepatobiliary Cancers V.2.2008 www.nccn.org Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® NCCN Hepatobiliary Cancers Panel Members Al B. Benson, III, MD/Chair Robert H. Lurie Comprehensive Cancer Center of Northwestern University Edgar Ben-Josef, MD University of Michigan Comprehensive Cancer Center Mark Bloomston, MD Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University Jean F. Botha, MB, BCh UNMC Eppley Cancer Center at The Nebraska Medical Center Bryan M. Clary, MD Duke Comprehensive Cancer Center Steven A. Curley, MD The University of Texas M. D. Anderson Cancer Center Michael I. D’Angelica, MD Memorial Sloan-Kettering Cancer Center † § ¶ ¶ ¶ ¶ ¶ James A. Posey, MD University of Alabama at Birmingham Comprehensive Cancer Center Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance † Riad Salem, MD, MBA Robert H. Lurie Comprehensive Cancer Center of Northwestern University Elin R. Sigurdson, MD, PhD Fox Chase Cancer Center Mika Sinanan, MD, PhD Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance Jean-Nicolas Vauthey, MD The University of Texas M. D. Anderson Cancer Center Alan P. Venook, MD UCSF Helen Diller Family Comprehensive Cancer Center Raymond S. W. Yeung, MD Lawrence D. Wagman, MD City of Hope § ¶ ¶ ¶ † ‡ ¶ ¶ Hepatobiliary Cancers William D. Ensminger, MD, PhD University of Michigan Comprehensive Cancer Center Christopher Garrett, MD John F. Gibbs, MD Roswell Park Cancer Institute Rene Davila, MD St. Jude Children’s Research Hospital/ University of Tennessee Cancer Institute Craig C. Earle, MD, MSc Dana-Farber/ Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida Daniel Laheru, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Sean J. Mulvihill, MD Huntsman Cancer Institute at the University of Utah Þ † † ¶ † Þ ¶ † * * * † Medical Oncology § Radiotherapy/Radiation Oncology/Interventional Radiology ¶ Surgery/Surgical Oncology Þ Internal Medicine ‡ Hematology/Hematology Oncology *Writing Committee Member Continue Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® This manuscript is being updated to correspond with the newly updated algorithm. Table of Contents Hepatocellular Carcinoma: Gallbladder Cancer: NCCN Hepatobiliary Cancers Panel Members Extrahepatic Cholangiocarcinoma (EXTRA-1) Guidelines Index Print the Hepatobiliary Cancers Guideline Summary of Guidelines Updates Clinical Presentation and Workup (HCC-1) Potentially resectable, operable (HCC-2) Unresectable or patient declines surgery (HCC-3) Inoperable, local disease (HCC-4) Metastatic disease (HCC-4) CHILD-PUGH Score (HCC-A) Incidental finding at surgery (GALL-1) Incidental finding on pathologic review (GALL-1) Mass on imaging (GALL-2) Jaundice (GALL-2) Metastatic disease (GALL-2) � � � � � � � � � Intrahepatic Cholangiocarcinoma (INTRA-1) These guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2007. For help using these documents, please click here Staging Manuscript References Clinical Trials: Categories of Evidence and Consensus: NCCN The believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. To find clinical trials online at NCCN member institutions, All recommendations are Category 2A unless otherwise specified. See NCCN click here: nccn.org/clinical_trials/physician.html NCCN Categories of Evidence and Consensus Hepatobiliary Cancers Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® UPDATES Hepatocellular Carcinoma HCC-3 : Footnote “e” regarding Child-Pugh score, now includes “and assessment of portal hypertension (eg, varices, splenomegaly, and thrombocytopenia).” Surgical Evaluation, Bottom branch: Included “....or hepatitis C antigen positive.” Footnote “i”: Removed the word “cadaveric” so that text now reads “Criteria for transplantation.” (Also for ) Footnote “k” that states, “For selected patients, a randomized clinical trial has demonstrated survival benefits” is new to the page. � � � � � � Treatment: The sorafenib recommendations now include Child- Pugh Class A , with corresponding footnote “l” that states, “There are limited safety data available for Child-Pugh Class B patients. Use with extreme caution in patients with elevated bilirubin levels.” Previously, the guidelines only recommended sorafenib for Child-Pugh Class A patients. (Also for ) Treatment, Top branch: Sorafenib was added as a treatment option for patients who are inoperable by performance status or comorbidity (local disease only) and who present with cancer- related symptoms. or B HCC-4 ( ) ( ) ( ) ( ) HCC-1 HCC-2 HCC-3 HCC-4 Summary of the Guidelines Updates Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Gallbladder Cancer Intrahepatic Cholangiocarcinoma Extrahepatic Cholangiocarcinoma : Top branch, second column: The phrase “Consider en bloc resection” was changed to “Consider extended cholecystectomy.” Postoperative Workup; Bottom branch: The recommendation “Strongly consider staging laparoscopy” was added. Resectable; Primary Treatment: Panel deleted the recommendation “± resection of port sites for laparoscopic operations.” Footnote “b” was amended with the following sentence: “Patients with nodal disease outside this area are unresectable.” Under Adjuvant Treatment: The panel changed “...chemotherapy/RT” to “...chemotherapy ± RT” : : Unresectable and metastatic pathways; Primary Treatment: The panel changed the recommendation to “Biliary drainage, Surgical Procedures for Resectable Disease box: Proximal Third: The panel changed “± en bloc liver resection” to “+” en bloc liver resection. � � � � � � � � � Workup: After “Upper and lower endoscopy”, the panel deleted the phrase “as indicated” Primary Treatment, Unresectable: The panel deleted the recommendation “Ablative or embolization therapy” along with its corresponding footnote. if indicated” ( ) ( ) ( ) GALL-1 INTRA-1 EXTRA-1 ( )GALL-3 Summary of the changes in the 1.2008 version of the Hepatobiliary Cancer guidelines from the 2.2007 version include: Hepatobiliary Cancers Summary of the changes in the 2.2008 version of the Hepatobiliary Cancer guidelines from the 1.2008 version include: The addition of sorafenib as a treatment option for patients who are inoperable by performance status or comorbidity (local disease only) and who do not present with cancer-related symptoms . Footnote “l” revised to read “ : There are limited safety data available for Child-Pugh Class B patients. Use with extreme caution in patients with elevated bilirubin levels” throughout the hepatocellular carcinoma guideline. � � Caution ( )HCC-4 Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. CLINICAL PRESENTATION Liver mass suspicious for hepatocellular carcinoma (HCC) or Histologically confirmed HCC WORKUP a c d e If ultrasound negative, CT/MRI should be performed. Rule out germ cell tumor if clinically indicated. MRI or triple phase CT scan may be helpful. An appropriate hepatitis panel should preferably include: and assessment of portal hypertension (eg, varices, splenomegaly, thrombocytopenia). bMRI/ CT scan to define extent and number of primary lesions, vascular anatomy, involvement with tumor, and extrahepatic disease; triphasic helical CT or MRI to include early arterial phase enhancement. � Hepatitis B surface antigen (HBsAg). HBe and anti-HBc (IgM) are included if HBsAg is positive Hepatitis B surface antibody (for HBIG or vaccine evaluation only) Hepatitis C virus antibodies. If low positive, recombinant immuno blot assay (RIBA) confirmation test is performed � � See Child-Pugh Score (HCC-A) Rising alpha- fetoprotein (AFP) Liver imaging studiesa,b INITIAL FINDINGS OF TUMOR AND LIVER FUNCTION Metastatic See Metastatic pathway (HCC-4) SURGICAL ASSESSMENT Mass confirmed No massc Screen every 3 mo with AFP, liver imaging Follow pathway for HCC, below � � � � � � � � H&P Hepatitis panel Bilirubin, trans- aminases, alkaline phosphatase, LDH, PT or INR, albumin, protein, BUN, creatinine CBC, platelets AFP CT/MRI Chest x-ray d b � � Hepatitis B surface antigen Hepatitis C antibodies Nonmetastatic Assess liver reserve and comorbidity Additional imaging as required: e � � � � � Chest CT Bone scan CT/MRI Arterial CT Ultrasound b Unresectable (See HCC-3) Inoperable by performance status or comorbidity, local disease only (See HCC-4) Metastatic disease (See HCC-4) Potentially resectable, operable liver mass (See HCC-2) HCC-1 Hepatocellular Carcinoma Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® Consider biopsy or Surgical evaluation f Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. SURGICAL EVALUATION Potentially resectable, operable liver mass (non-metastatic disease, liver confined) Surgical evaluation f Positive for HCC Nondiagnostic � � � Imaging follow-up Rebiopsy Surgery, including laparoscopy AFP > 4,000 ng/mL, surface antigen positive AFP > 400 ng/mL, surface antigen negative AFP < 400 ng/mL surface antigen negative or AFP < 4,000 ng/mL, hepatitis B surface antigen positive or hepatitis C antigen positive Positive for HCC TREATMENT Resectable: Resection ± ablation or Transplant h g i Unresectable Ablation� g Treatment (See HCC-3) See Surgical evaluation, above f g i Discussion of surgical treatment with patient and determination of whether patient is amenable to surgery. Ablation or embolization options: radiofrequency, alcohol, cryotherapy, microwave or embolization (chemoembolization, radioembolization, bland embolization). Consider interferon or other antiviral therapy for selected low risk hepatitis C patients with completely resected tumors and good performance status. Criteria for transplantion (UNOS criteria): Patient is not a liver resection candidate Patient has a tumor 5 cm in diameter or 2-3 tumors 3 cm each No macrovascular involvement No extrahepatic spread of tumor to surrounding lymph nodes, lungs, abdominal organs, or bone Mazzaferro V, Regalia E, Doci, R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334(11):693-700. h � � � � � � SURVEILLANCE � � Imaging every 3-6 mo for 2 y, then annually AFP, if initially elevated, every 3 mo for 2 y, then every 6 mo For relapse, see initial Workup (HCC-1) CLINICAL PRESENTATION HCC-2 See Surgical evaluation, above Patient does not agree to surgery Treatment (See HCC-3) or Ablation (category 2B) g Patient agrees to surgery Hepatocellular Carcinoma Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Unresectable or patient declines surgery Extensive Options: � � � � � � � � � Sorafenib (Child-Pugh Class A or B) , Chemoembolization Clinical trial Ablation Chemotherapy + RT in clinical trial RT (conformal or stereotactic) Radioembolization Supportive care Systemic or intra-arterial chemotherapy in clinical trial e j,k,l m g TREATMENT � � Inadequate hepatic reserve Tumor location e Evaluate whether patient a candidate for transplanti Cancer-related symptoms absent Sorafenib (Child-Pugh Class A or B) ,e j,k,l or Clinical trial Transplant candidate Not a transplant candidate Transplant Cancer-related symptoms present (UNOS criteria): Patient is not a liver resection candidate Patient has a tumor 5 cm in diameter or 2-3 tumors 3 cm each No macrovascular involvement No extrahepatic spread of tumor to surrounding lymph nodes, lungs, abdominal organs, or bone Contraindicated in cases of main portal thrombosis or Child-Pugh Class C. e j k l g i m Ablation or embolization options: radiofrequency, alcohol, cryotherapy, microwave or embolization (chemoembolization, radioembolization, bland embolization). Criteria for transplantion Mazzaferro V, Regalia E, Doci, R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334(11):693-700. The impact of sorafenib on patients potentially eligible for transplant is unknown. Data are inadequate to define dosing for patients with abnormal liver function (Child-Pugh Class B or C). . (Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial). 2007 ASCO Annual Meeting Proceedings Part I. J Clin Onc 2007, Vol 25, No. 18S (June 20 Supplement), 2007: LBA1) Caution: There are limited safety data available for Child-Pugh Class B patients. Use with extreme caution in patients with elevated bilirubin levels. (Miller AA, Murry K, Owzar DR, et al. Pharmacokinetic (PK) phase I study of sorafenib (S) for solid tumors and hematologic malignancies with hepatic or renal dysfunction (HD or RD): CALGB 6031 2007 ASCO Annual Meeting Proceedings Part I. J Clin Onc 2007, Vol 25, No 18S (June 20 Supplement), 2007: 3538) � � � � � � For selected patients, a randomized clinical trial has demonstrated survival benefits See Child-Pugh Score (HCC-A). SURVEILLANCE � � Imaging every 3-6 mo for 2 y, then annually AFP, if initially elevated, every 3 mo for 2 y, then every 6 mo CLINICAL PRESENTATION HCC-3 Hepatocellular Carcinoma Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN. Practice Guidelines in Oncology – v.2.2008 Guidelines Index Hepatobiliary Cancers TOC Staging, MS, ReferencesNCCN ® Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Metastatic disease Inoperable by performance status or comorbidity, local disease only � � AFP > 4,000 ng/mL, surface antigen positive (Biopsy not required) AFP > 400 ng/mL, surface antigen negative (Biopsy not required) AFP < 400 ng/mL surface antigen negative or AFP < 4,000 ng/mL, hepatitis B surface antigen positive Options: � � � � � � � Sorafenib (Child-Pugh Class A or B) , Clinical trial Ablation Chemoembolization RT (conformal or stereotactic) Radioembolization Supportive care e j,k,l g m TREATMENT Cancer-related symptoms absent Cancer-related symptoms present Consider biopsy HCC confirmed e j k l g m Ablation or embolization options: radiofrequency, alcohol, cryotherapy, microwave or embolization (chemoembolization, radioembolization, bland embolization) The impact of sorafenib on patients potentially eligible for transplant is unknown. Data are inadequate to define dosing for patients with abnormal liver function (Child-Pugh Class B or C). . (Llovet J, Ricci S, Mazzaferro V, et al. Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial). 2007 ASCO Annual Meeting Proceedings Part I. J Clin Onc 2007, Vol 25, No. 18S (June 20 Supplement), 2007: LBA1. Caution: There are limited safety data available for Child-Pugh Class B patients. Use with extreme caution in patients with elevated bilirubin levels. (Miller AA, Murry K, Owzar DR, et al. Pharmacokinetic (PK) phase I study of sorafenib (S) for solid tumors and hematologic malignancies with hepatic or renal dysfunction (HD or RD): CALGB 6031 2007 ASCO Annual Meeting Proceedings Part I. J Clin Onc 2007, Vol 25, No 18S (June 20 Supplement), 2007: 3538) For selected patients, a randomized clinical trial has demonstrated survival benefits Contraindicated in cases of main portal thrombosis or Child-Pugh Class C. See Child-Pugh Score (HCC-A). CLINICAL PRESENTATION HCC-4 Hepatocellular Carcinoma Sorafenib (Child-Pugh Class A or B) ,e j,k,l or Supportive care or Clinical trial Sorafenib (Child-Pugh Class A or B) ,e j,k,l or Ablation or Clinical trial Version 2.2008, 10/31/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without t