eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Fibrolamellar Carcinoma: Treatment & Medication

Author: Michael A Choti, MD, MBA, Jacob C Handelsman Professor of Surgery, Professor of Oncology and Engineering, Johns Hopkins University School of Medicine
Coauthor(s): Hari Nathan, MD, House Staff, Department of Surgery, The Johns Hopkins Hospital; Postdoctoral Fellow, Department of Surgery, The Johns Hopkins University School of Medicine
Contributor Information and Disclosures

Updated: Mar 9, 2009

Treatment

Medical Care

  • Surgical resection or transplantation is the standard of care for fibrolamellar carcinoma (FLC) for eligible patients.
  • Trans-arterial chemo-embolization (TACE) may be a useful option in patients who have unresectable disease.68,69 Chemotherapy for metastatic disease is as for metastatic typical hepatocellular carcinoma (HCC). Single agent chemotherapy or combinations of chemotherapeutic drugs give responses of no more than 25% with questionable benefit for overall survival.
  • Sorafenib is an orally delivered small molecule that inhibits several different protein kinases, including Raf-1 and B-Raf, platelet-derived growth factor β (PDGFR-β), and vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. Sorafenib targets both tumor growth (Raf-MEK-ERK pathway) and neoangiogenesis (VEGFRs, PDGFR-β), both of which are thought to be important in the pathogenesis of typical hepatocellular carcinoma.
    • A randomized controlled trial of sorafenib in 602 patients with advanced typical hepatocellular carcinoma, and well-compensated cirrhosis demonstrated a survival benefit with sorafenib as compared to placebo, corresponding to a 3-month increase in median survival (10.7 versus 7.9 mo).70
    • A similar study will likely never be performed in fibrolamellar carcinoma due to the rarity of the disease. It is unclear whether the data on sorafenib for typical hepatocellular carcinoma are generalizable to fibrolamellar carcinoma. There are not yet any reports in the literature describing sorafenib use in fibrolamellar carcinoma.
  • A phase II clinical trial reported in 2003 evaluated 21-day courses of systemic continuous 5-fluorouracil repeated monthly and thrice-weekly subcutaneous recombinant interferon α-2b in a mixed population of 43 patients with fibrolamellar carcinoma and typical hepatocellular carcinoma.71 All of these patients were ineligible for surgical therapy due to extent of hepatic disease as determined by CT scan, but none had extrahepatic disease. Of 9 patients with fibrolamellar carcinoma, 8 were radiologically assessed for response. Among these 8 patients, there were 1 complete response (CR), 4 partial responses (PR), and 1 minor response (MR). The medial survival of the fibrolamellar carcinoma patients was 23 months, compared to 15.5 months for typical hepatocellular carcinoma (statistical significance not reported).
    • Of note, a major reason that the authors chose this treatment regimen was that they anticipated that it would be well-tolerated by patients with cirrhosis. Although the regimen was well-tolerated in this trial, none of the fibrolamellar carcinoma patients in fact had cirrhosis.
    • Because fibrolamellar carcinoma patients generally do not have cirrhosis, chemotherapeutic regimens that might not appropriate for typical hepatocellular carcinoma might be of use in fibrolamellar carcinoma.
  • Pediatric Intergroup Hepatoma Protocol INT-0098 enrolled 46 patients with hepatocellular carcinoma from 1989-1992, of whom 10 had fibrolamellar carcinoma and the remainder typical hepatocellular carcinoma.18 Of the 10 patients with fibrolamellar carcinoma, 2 initially underwent R0 resection, 6 underwent R2 resection, and 2 were found to have metastatic disease and underwent either debulking or biopsy. Subsequently, 7 of these patients (both R0, 3 R2, and 2 metastatic) received chemotherapy with cisplatin/doxorubicin, and 3 (all R2) received cisplatin/vincristine/doxorubicin. The median survival of the fibrolamellar carcinoma patients was 13.6 months, compared with 3.3 months for typical hepatocellular carcinoma. This difference was not statistically significant and should be cautiously interpreted due to the small sample size and because this was a subset analysis of a larger trial.

Surgical Care

  • General principles
    • Optimal management for most hepatic malignancies, including typical hepatocellular carcinoma and fibrolamellar carcinoma, is complete surgical resection (eg, wedge resection, anatomic liver resection, or total hepatectomy with orthotopic liver transplantation).
    • There may be occasional utility in treating fibrolamellar carcinoma with neoadjuvant chemotherapy or trans-arterial chemo-embolization (TACE) with the goal of downstaging the tumor to allow resection.68
  • Hepatic resection
    • Cirrhosis often limits the feasibility of liver resection in patients with typical hepatocellular carcinoma because cirrhotic patients have increased perioperative risk and require a larger future liver remnant (FLR) to be left behind to allow adequate liver function.
    • Unlike typical hepatocellular carcinoma, fibrolamellar carcinoma is rarely associated with cirrhosis, and patients are often young and otherwise healthy. For this reason, aggressive liver resections can be more readily undertaken in fibrolamellar carcinoma patients than in typical hepatocellular carcinoma patients.
    • Only a few modern surgical series of liver resection for fibrolamellar carcinoma have been published, as follows:
      • Pinna (1997) reported the results of 28 patients undergoing liver resection for fibrolamellar carcinoma, with survival greater than 85% at 3 years and greater than 80% at 5 years. Tumor recurrence was found in 18 patients.63
      • Kakar (2005) reported the results of 20 patients undergoing liver resection for fibrolamellar carcinoma and compared the results to those for typical hepatocellular carcinoma. Five-year survival was 45%, similar to that found in hepatocellular carcinoma without cirrhosis but significantly better than in hepatocellular carcinoma with cirrhosis.20
      • Stipa (2006) reported the results of 28 patients undergoing liver resection for fibrolamellar carcinoma, with median survival of 112 months (versus 37 months for typical hepatocellular carcinoma) and 5-year survival of 76% (versus 37% for typical hepatocellular carcinoma). Median recurrence-free survival was 33 months, and 5-year recurrence-free survival was 18%.35
    • Patients with resected fibrolamellar carcinoma generally have a prognosis similar to that for noncirrhotic patients with resected typical hepatocellular carcinoma.20,19 Aggressive surgical approaches, even for recurrent disease, can be undertaken with good results.22
  • Orthotopic liver transplantation
    • Total hepatectomy followed by orthotopic liver transplantation (OLT) should be considered in patients with unresectable fibrolamellar carcinoma that is confined to the liver.
    • Reports of liver transplantation for fibrolamellar carcinoma are confined to small series, the most recent of which are summarized below:
      • Pichlmayr (1997) reported the results of a large series of liver transplants performed for hepatobiliary malignancies, including 124 for typical hepatocellular carcinoma and 8 for fibrolamellar carcinoma. Hepatocellular carcinoma patients in this series had 1-year, 5-year, and 10-year survival rates of 53%, 26%, and 19%, respectively. The median survival was 13 months. No difference in outcomes was seen in patients with hepatocellular carcinoma with and without cirrhosis. Patients with fibrolamellar carcinoma in this series had superior prognoses, with 1-year, 5-year, and 10-year survival of 63%, 38%, and 25%, respectively. The median survival was 35 months.72
      • Pinna (1997) reported the results of 13 liver transplants for fibrolamellar carcinoma, with survival of approximately 45% at 3 years and approximately 35% at 5 years.63
      • El-Gazzaz (2000) reported the results of 9 liver transplants for fibrolamellar carcinoma, with 1-year, 3-year, and 5-year survival of 90%, 75%, and 50%, respectively.23
    • Even among patients who develop tumor recurrence, the time to recurrence is significantly longer in patients with fibrolamellar carcinoma than among those with typical hepatocellular carcinoma.73 This may be a result of more indolent behavior by fibrolamellar carcinoma versus typical hepatocellular carcinoma. Alternatively, it may result from the fact that accompanying cirrhosis in typical hepatocellular carcinoma increases the risk of recurrence (including development of a second primary tumor) via a field effect.
    • Orthotopic liver transplantation can result in long-term survival but is a resource-intensive treatment approach. In typical hepatocellular carcinoma, orthotopic liver transplantation confers the advantage of removing the at-risk cirrhotic liver in addition to the tumor itself. In fibrolamellar carcinoma, this theoretical advantage is likely not present because there is no such field effect at work (due to the lack of cirrhosis in most cases). As such, it is not clear that the use of donor organs in patients with fibrolamellar carcinoma is an appropriate use of this scarce resource.70 Newer innovative approaches (eg, adult living-related donations, split-liver techniques, and potential use of marginal donor organs) may allow for a future increase in the use of orthotopic liver transplantation for fibrolamellar carcinoma.

More on Fibrolamellar Carcinoma

Overview: Fibrolamellar Carcinoma
Differential Diagnoses & Workup: Fibrolamellar Carcinoma
Treatment & Medication: Fibrolamellar Carcinoma
Follow-up: Fibrolamellar Carcinoma
Multimedia: Fibrolamellar Carcinoma
References
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Further Reading

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Keywords

fibrolamellar carcinoma review article, fibrolamellar cancer review article, fibrolamellar cancer treatment, fibrolamellar cancer diagnosis, fibrolamellar cancer pictures, fibrolamellar cancer image, fibrolamellar carcinoma treatment, fibrolamellar carcinoma diagnosis, fibrolamellar carcinoma pictures, fibrolamellar carcinoma images, liver tumor, liver cancer, hepatic cancer, fibrolamellar hepatoma, hepatocellular carcinoma with lamellar fibrosis, FLC, hepatocellular cancer, HCC, eosinophilic hepatocellular carcinoma with lamellar fibrosis, polygonal cell with fibrous stroma, eosinophilic glassy cell hepatoma, fibrolamellar oncocytic hepatoma, fibrolamellar carcinoma

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Contributor Information and Disclosures

Author

Michael A Choti, MD, MBA, Jacob C Handelsman Professor of Surgery, Professor of Oncology and Engineering, Johns Hopkins University School of Medicine
Michael A Choti, MD, MBA is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Surgeons, American Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology, American Surgical Association, Association for Academic Surgery, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, Society of Surgical Oncology, and Society of University Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Hari Nathan, MD, House Staff, Department of Surgery, The Johns Hopkins Hospital; Postdoctoral Fellow, Department of Surgery, The Johns Hopkins University School of Medicine
Hari Nathan, MD is a member of the following medical societies: American College of Surgeons, American Hepato-Pancreato-Biliary Association, Association for Academic Surgery, and Society for Surgery of the Alimentary Tract
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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