Staging of HcC.docx

1、Staging of HcC10.1148/rg.25si055507 October 2005 RadioGraphics, 25, S3-S23Staging and Current Treatment of Hepatocellular CarcinomaHollins P. Clark, MD, W. Forrest Carson, MD, Peter V. Kavanagh, MD, Coty P. H. Ho, MD, Perry Shen, MD and Ronald J. Zagoria, MD 1 From the Departments of Radiology (H.P.

2、C., W.F.C., P.V.K., R.J.Z.), Internal Medicine (C.P.H.H.), and Surgery (P.S.), Wake Forest University School of Medicine, Meads Hall, 2nd Floor, Medical Center Blvd, Winston-Salem, NC 27157-1088. Presented as an education exhibit at the 2004 RSNA Annual Meeting. Received February 8, 2005; revision r

3、equested March 29 and received May 24; accepted May 31. The article discusses an investigational or unlabeled use of a commercial device or pharmaceutical that has not been approved for such purpose by the FDA. TheraSphere (MDS Nordion, Ottawa, Ontario, Canada) has received humanitarian device exemp

4、tion approval from the U.S. FDA for treatment of unresectable hepatocellular carcinoma and can be used only in an investigational capacity. SIR-Spheres (Sirtex Medical, Lake Forest, Ill) has received premarket approval from the FDA for use in combination with hepatic arterial fluorouracil therapy to

5、 treat colorectal metastasis to the liver; its use for treatment of primary hepatic neoplastic disease is an off-label application. Likewise, intraarterial administration of cisplatin, doxorubicin, and mitomycin C for treatment of hepatocellular carcinoma constitutes off-label use of these pharmacol

6、ogic products. All authors have no financial relationships to disclose. Address correspondence to H.P.C. (e-mail: hclarkwfubmc.edu ). AbstractEarly-stage hepatocellular carcinoma (HCC) is typically clinically silent, and HCC is often advanced at first manifestation. Without treatment, the 5-year sur

7、vival rate is less than 5%. The selected treatment depends on the presence of comorbidity; tumor size, location, and morphology; and the presence of metastatic disease. Complete surgical resection followed by hepatic transplantation offers the best long-term survival, but few patients are eligible f

8、or this therapy. All other therapies are palliative. Radiofrequency ablation is the preferred method for managing unresectable small HCCs that are few in number. More widespread disease is treated with percutaneous therapies such as chemoembolization and selective internal radiation therapy. Systemi

9、c administration of biologic and chemotherapeutic agents is minimally successful in slowing the growth of HCC and typically is used to control symptoms in patients with overwhelming disease. A multidisciplinary approach that includes surgery, systemic therapy, and radiation therapy and that is based

10、 on the cooperation of radiation oncologists, interventional and diagnostic radiologists, hepatologists, and pathologists may offer the best chance of a cure or at least a longer and more normal life. To participate effectively in this effort, radiologists must be familiar with staging and treatment

11、 options for HCC and with the factors that affect the choice of management method. RSNA, 2005 LEARNING OBJECTIVES FOR TEST 1After reading this article and taking the test, the reader will be able to: Identify the anatomic and clinical parameters that influence the treatment options and prognosis for

12、 patients with hepatocellular carcinoma. Discuss the evolving role of image-guided therapies in the treatment of hepatocellular carcinoma. Describe the limitations of traditional surgical and medical management of hepatocellular carcinoma. IntroductionHepatocellular carcinoma (HCC) is the cause of 2

13、50,000 deaths worldwide each year. Early HCC is typically clinically silent, and the disease is often well advanced at the first manifestation. Without treatment, there is a 5-year survival rate of less than 5% (1). According to the World Health Organization, by the year 2010, HCC will have surpasse

14、d lung cancer as the foremost cause of cancer mortality (2). In the United States alone, the incidence of histologically proved HCC increased from 1.4 of 100,000 people in the 19761980 population to 2.4 of 100,000 people in the 19911995 population (3). HCC predominantly affects the elderly, and inve

15、stigators in a recent study of Medicare patients found that the age-adjusted incidence of HCC among individuals 65 years and older had increased from 14.2 per 100,000 in 1993 to 18.1 per 100,000 in 1999 (4). The increasing incidence in this age group may be related to the widespread transmission of

16、viral hepatitis, specifically of types B and C, during the late 1960s and 1970s, when illicit use of intravenous narcotics, needle sharing, unsafe sexual activity, and transfusion of unsafe blood and blood products were common practices (3). A diagnosis of HCC implies a poor prognosis. Currently, lo

17、ng-term survival is best achieved through surgical management. However, only about 20% of patients are surgical candidates at initial manifestation of HCC (5). Overall survival for patients with unresectable disease is based on tumor stage and size, liver function, and symptoms. Llovet et al (6), in

18、 a study of 102 patients with unresectable HCC, determined that survival was 54% at 1 year, 40% at 2 years, and 28% at 3 years. Many treatment options have been developed to improve the quality and duration of life for patients with unresectable HCC. Presently, in the United States, commonly used pa

19、lliative therapies include systemic therapies, radiofrequency (RF) ablation, transarterial chemoembolization (TACE), and selective internal radiation therapy. In this article, we review the triage of patients with HCC among the various treatment options (Fig 1) and analyze the capacity of each treat

20、ment to prolong and to improve the quality of life. However, this review is only a broad outline. Individual case management and treatment effectiveness are influenced by many intangible and unpredictable factors. Figure 1. Flowchart shows the algorithm used for selecting the appropriate treatment f

21、or HCC when the principal alternatives are surgical resection (the preferred treatment method), transplantation, RF ablation, TACE, selective internal radiation therapy (SIRT), systemic therapy, and supportive care. Treatment for unresectable HCC is selected on the basis of clinical and imaging find

22、ings. Staging of HCCCancer staging is an ever-evolving process that is important for both patient management and research advancement. At present, multiple staging systems for HCC are recognized. Several staging systems incorporate various clinical and radiologic parameters into integrated scoring s

23、chemes (Okuda, Barcelona Clinic Liver Cancer, and Cancer of the Liver Italian Program CLIP). These medical staging systems are most applicable to patients with advanced disease who are not considered candidates for surgery. Systems of staging that are based on the results of pathologic analysis (eg,

24、 American Joint Committee on Cancer AJCC/Union Internationale Contre le Cancer UICC and Liver Cancer Study Group of Japan classification systems) incorporate anatomic and histologic findings at tumor resection (7). Given the heterogeneity of patients with HCC and the small percentage who are surgica

25、l candidates, both the clinical and the histopathologic systems of staging are needed. In a 2002 consensus statement, the American Hepato-Pancreato-Biliary Association and the AJCC advocated the use of the CLIP classification system for medical staging because that system has been well validated, is

26、 applicable to most patients, and includes easily collected data (8,9). For patients with resectable disease, the AJCC/UICC staging system is most useful, because it too has been validated, it is based on the standard system of tumor, node, and metastasis classification, and it can be applied after

27、resection or transplantation (9,10). At the First International Symposium on Image-guided Therapy for Cancer, in May 2005, Jean-Nicolas Vauthey, MD, chief of the Liver Service in the Department of Surgical Oncology at the University of Texas M. D. Anderson Cancer Center, Houston, Tex, presented a st

28、rong argument for acceptance of the AJCC/UICC system because of its capacity to help more accurately predict the prognosis and to direct postoperative adjuvant therapy (7). However, the United Network of Organ Sharing also recognizes the modified tumor, node, and metastasis classification system dev

29、eloped by the American Liver Tumor Study Group for assessment of HCC in patients considered for liver transplantation (Tables 1 3) (11,12). Table 1. CLIP Scoring SystemNote.Adapted, with permission, from reference 7; data are derived from reference 8. Table 2. AJCC/UICC Classification System Note.Ad

30、apted, with permission, from reference 7; data are derived from reference 10Table 3. American Liver Tumor Study Group Modified TNM Classification and Staging SystemNote.Adapted, with permission, from references 11 and 12. Surgical TreatmentComplete surgical resection and hepatic transplantation offe

31、r the best chance of a cure for HCC. However, surgery is often precluded by extensive disease or poor hepatic functional reserve (Figs 2, 3). Furthermore, patient selection and outcome are inevitably influenced by the skill and experience of the surgeon. Even with surgical resection, the overall 5-y

32、ear survival is approximately 30% (13).Figure 2a. Unresectable HCC in a 48-year-old man. (a) Contrast-enhanced portal phase CT image shows HCC that involves liver segment V (black arrow) and the gallbladder (white arrow). Figure 2b. Unresectable HCC in a 48-year-old man. (b) Contrast-enhanced portal phase CT image obtained at a lower level than a shows enlarged portal lymph nodes (arrowhead), which proved to be metastatic disease at histopathologic analysis after fine-needle aspiration performed with endoscopic US guidance. Figure 2c. Unresectable HCC in