F-Fluorodeoxyglucose Positron Emission Tomography in Detecting Extrahepatic Metastasis in Pretreatment Staging of Hepatocellular Carcinoma

Objectives: 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for differentiating benign from malignant lesions, evaluating tumor stage, monitoring the response to therapy and detecting tumor recurrence in a variety of malignancies. Nevertheless, its use in patients with hepatocellular carcinoma (HCC) is still uncertain. We evaluated whether FDG-PET has a role in detecting extrahepatic metastasis in pretreatment tumor staging of HCC and the characteristics of patients with extrahepatic metastasis that benefit from FDG-PET. Methods: Eighty-seven patients with HCC underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and chest X-ray to evaluate pretreatment tumor staging. FDG-PET was then performed to detect extrahepatic metastasis. The power of FDG-PET to detect extrahepatic metastasis was compared with that of conventional images. In addition, we evaluated whether the detection of extrahepatic metastasis using FDG-PET changed the TNM stage. Moreover, we invesPublished online: December 13, 2007 Oncology Kwang-Hyub Han Department of Internal Medicine, Yonsei University College of Medicine Yonsei Liver Cancer Special Clinic, Severance Hospital 250 Seongsanno, Seodaemun-gu, Seoul 120-752 (Korea) Tel. +82 2 2228 1949, Fax +82 2 393 6884, E-Mail gihankhys@yumc.yonsei. ac.kr © 2007 S. Karger AG, Basel 0030–2414/07/0727–0104$23.50/0 Accessible online at: www.karger. com/ocl Role of FDG-PET in Detecting Extrahepatic Metastasis of HCC Oncology 2007;72(suppl 1):104–110 105 response in a variety of malignant tumors [1, 2] . However, the role of FDG-PET remains limited in the screening or diagnosis of primary hepatocellular carcinoma (HCC) because of its low sensitivity and high cost [3, 4] . Extrahepatic metastases of HCC are not rare [5, 6] . When there are no extrahepatic metastases in advanced HCC, aggressive locoregional intervention is possible. However, the presence of extrahepatic spread from HCC is categorized as systemic disease and the treatment is limited and has a poor prognosis [7] . Therefore, accurate staging of HCC is critical. Widely accepted imaging modalities for staging HCC are triple-phase computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI), which have accuracies exceeding 80% [8, 9] . Nevertheless, CT and MRI have a limited ability to identify distant metastases [10] . Previous studies have reported the role of FDG-PET in detecting distant metastasis in a variety of malignancies [2] . In HCC, one study showed that FDG uptake pattern is closely correlated to the gene expression and molecular markers involved in tumor progression and metastasis [11] . Therefore, it is necessary to identify the role of FDG-PET in detecting extrahepatic metastasis in pretreatment tumor staging. If it has a role, it is important to investigate which patients need FDG-PET because it may not be cost-effective to use FDG-PET for all HCC patients. We compared the power of FDG-PET to detect extrahepatic metastasis in pretreatment tumor staging with that of conventional images and examined the characteristics of patients with extrahepatic metastasis of HCC. Materials and Methods Patients Between January 2002 and December 2004, 87 consecutive patients with HCC were enrolled. All patients underwent triplephase CT or contrast-enhanced MRI of the abdomen to evaluate intrahepatic HCC and extrahepatic metastasis. In addition, chest X-ray was used to detect lung metastasis. We called this process the conventional staging workup. After the conventional staging workup, FDG-PET was performed to detect occult extrahepatic metastasis. If a lesion suspicious of extrahepatic metastasis was detected in a conventional image or FDG-PET, an additional diagnostic workup consisting of chest CT and a whole-body bone scan (WBBS) or MRI of the bone was performed. Extrahepatic metastasis was confirmed radiologically and at clinical follow-up at least 3 months after FDG-PET. We compared the power of FDG-PET and conventional images to detect extrahepatic metastasis. In addition, we evaluated whether the detection of additional extrahepatic metastasis using FDG-PET changed the TNM stage. Data collected to examine the characteristics of patients with extrahepatic metastasis included gender, age, etiology of liver disease, Child-Pugh classification, alpha-fetoprotein (AFP) levels, protein induced by vitamin K antagonist II (PIVKA-II) levels, primary tumor number (single or multiple), primary tumor shape (nodular or infiltrative), primary tumor size (maximum diameter), and presence of portal vein thrombosis. PET Procedure and Interpretation Before treatment, the patients were examined using a wholebody PET camera (GE Advance, Milwaukee, Wisc., USA) prior to treatment. All patients fasted for at least 6 h before the study. Approximately 370 MBq of 18 F-FDG was injected intravenously and an emission scan (5 min/bed position) was performed from the neck to the knees 50–60 min after 18 F-FDG injection in the 2D mode. A transmission scan (3 min/bed position) was then performed using a rotating 68-Ge source. The images were reconstructed using the attenuation-corrected ordered subset expectation maximization algorithm (16 subsets, 2 iterations). The PET images were compared with the corresponding CT or MRI images for accurate tumor localization. Two specialists in nuclear medicine evaluated the coronal, sagittal, and axial images qualitatively to assess whether FDG uptake in the tumor was higher than that in the surrounding noncancerous tissue (positive vs. negative, respectively). Table 1. Patient demographics and baseline characteristics Patient characteristics n % Age, years1 54.0 (35–74) Sex Male 68 78.2 Female 19 21.8 Etiology of liver disease HBV 69 79.3 HCV 9 10.3 Alcohol 2 2.3 Unknown 7 8.0 Child-Pugh classification A 70 80.5 B 15 17.2 C 2 2.3 Tumor stage2 I 3 3.4 II 17 19.5 III 25 28.7 IVa 20 23.0 IVb 22 25.3 Extrahepatic metastases 24 27.6 Lung 12 13.8 Lymph node 19 21.8 Bone 11 12.6 1 Median (range). 2 Tumor stage based on the modified UICC TNM staging system.