[18 F]-Fluoro-2-deoxy-D-galactose positron emission tomography/computed tomography as complementary imaging tool in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Positron emission tomography (PET) with the liver-specific tracer [18 F]-fluoro-2-deoxy-D-galactose (18 F-FDGal) can be used for imaging of hepatocellular carcinoma (HCC). Curative intended and locoregional treatments of HCC require absence of extrahepatic disease. The aim of this prospective study was to determine whether adding 18 F-FDGal PET/CT to standard work-up changes the planned treatment in patients with HCC deemed suitable for curative or locoregional treatment. METHODS: Fifty patients with HCC were included at our tertiary liver centre. The primary study outcome was a change in treatment strategy. A subgroup of 29 patients was also examined with [18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) PET/CT for comparison. RESULTS: 18 F-FDGal PET/CT detected eight extrahepatic HCC metastases in six patients (12%), which were primarily not detected by ceCT or MRI. These findings led to a change in treatment in five patients (10%). One of the eight extrahepatic HCC foci was also detected by 18 F-FDG PET/CT. A total of 85 malignant intrahepatic foci were examined, 12 of these were new findings by 18 F-FDGal PET/CT which had a sensitivity of 71%, highest for large foci. None of the additional intrahepatic foci found by 18 F-FDGal PET changed the planned treatment. CONCLUSIONS: For the detection of extrahepatic HCC metastases, 18 F-FDGal PET/CT was superior both to standard clinical work-up with contrast-enhanced CT, and/or MRI, and to 18 F-FDG PET/CT in patients deemed suitable for locoregional treatment. 18 F-FDGal PET/CT led to a change in the planned treatment in 10% of the patients whereas 18 F-FDG PET/CT did not change the planned treatment in any patient.

Prognostic modeling for patients with colorectal liver metastases incorporating FDG PET radiomic features.

OBJECTIVE: We aimed to improve prediction of outcome for patients with colorectal liver metastases, via prognostic models incorporating PET-derived measures, including radiomic features that move beyond conventional standard uptake value (SUV) measures. PATIENTS AND METHODS: A range of parameters including volumetric and heterogeneity measures were derived from FDG PET images of 52 patients with colorectal intrahepatic-only metastases (29 males and 23 females; mean age 62.9 years [SD 9.8; range 32-82]). The patients underwent PET/CT imaging as part of the clinical workup prior to final decision on treatment. Univariate and multivariate models were implemented, which included statistical considerations (to discourage false discovery and overfitting), to predict overall survival (OS), progression-free survival (PFS) and event-free survival (EFS). Kaplan-Meier survival analyses were performed, where the subjects were divided into high-risk and low-risk groups, from which the hazard ratios (HR) were computed via Cox proportional hazards regression. RESULTS: Commonly-invoked SUV metrics performed relatively poorly for different prediction tasks (SUVmax HR = 1.48, 0.83 and 1.16; SUVpeak HR = 2.05, 1.93, and 1.64, for OS, PFS and EFS, respectively). By contrast, the number of liver metastases and metabolic tumor volume (MTV) each performed well (with respective HR values of 2.71, 2.61 and 2.42, and 2.62, 1.96 and 2.29, for OS, PFS and EFS). Total lesion glycolysis (TLG) also resulted in similar performance as MTV. Multivariate prognostic modeling incorporating different features (including those quantifying intra-tumor heterogeneity) resulted in further enhanced prediction. Specifically, HR values of 4.29, 4.02 and 3.20 (p-values = 0.00004, 0.0019 and 0.0002) were obtained for OS, PFS and EFS, respectively. CONCLUSIONS: PET-derived measures beyond commonly invoked SUV parameters hold significant potential towards improved prediction of clinical outcome in patients with liver metastases, especially when utilizing multivariate models.

A phase I study on stereotactic body radiotherapy of liver metastases based on functional treatment planning using positron emission tomography with 2-[18F]fluoro-2-deoxy-d-galactose.

BACKGROUND AND PURPOSE: The galactose analog 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) is used for quantification of regional hepatic metabolic capacity by functional positron emission tomography computerized tomography (PET/CT). In the present study, FDGal PET/CT was used for functional treatment planning (FTP) of stereotactic body radiotherapy (SBRT) of liver metastases with the aim of minimizing radiation dose to the best functioning liver tissue. MATERIAL AND METHODS: Fourteen patients referred for SBRT had FDGal PET/CT performed before and one month after the treatment. The planning CT and the FDGal PET/CT images were deformable co-registered. RESULTS: A reduction in the mean dose of approximately 2 Gy to the best functioning sub-volumes was obtained. One patient developed grade 2 acute morbidity and no patients experienced grade 3 or higher acute morbidities. The regional hepatic metabolic function post-treatment was linearly correlated to the regional radiation dose and for each 10-Gy increase in dose (γ10Gy), the metabolic function was reduced by 12%. A 50% reduction was seen at 22.9 Gy in 3 fractions (CI 95%: 16.7-30.4 Gy). CONCLUSION: The clinical study demonstrates the feasibility for FTP in patients with liver metastases and it was possible to minimize the radiation dose to the best functioning liver tissue.

Metabolic liver function in humans measured by 2-18F-fluoro-2-deoxy-D-galactose PET/CT-reproducibility and clinical potential.

BACKGROUND: PET/CT with the radioactively labelled galactose analogue 2-18F-fluoro-2-deoxy-D-galactose (18F-FDGal) can be used to quantify the hepatic metabolic function and visualise regional metabolic heterogeneity. We determined the day-to-day variation in humans with and without liver disease. Furthermore, we examined whether the standardised uptake value (SUV) of 18F-FDGal from static scans can substitute the hepatic systemic clearance of 18F-FDGal (K met, mL blood/min/mL liver tissue/) quantified from dynamic scans as measure of metabolic function. Four patients with cirrhosis and six healthy subjects underwent two 18F-FDGal PET/CT scans within a median interval of 15 days for determination of day-to-day variation. The correlation between K met and SUV was examined using scan data and measured arterial blood concentrations of 18F-FDGal (blood samples) from 14 subjects from previous studies. Regional and whole-liver values of K met and SUV along with total metabolic liver volume and total metabolic liver function (total SUV, average SUV multiplied by total metabolic liver volume) were calculated. RESULTS: No significant day-to-day differences were found for K met or SUV. SUV had higher intraclass correlation coefficients than K met (0.92-0.97 vs. 0.49-0.78). The relationship between K met and SUV was linear. Total metabolic liver volume had non-significant day-to-day variation (median difference 50 mL liver tissue; P = 0.6). Mean total SUV in healthy subjects was 23,840 (95% CI, 21,609; 26,070), significantly higher than in the patients (P < 0.001). CONCLUSIONS: The reproducibility of 18F-FDGal PET/CT was good and SUV can substitute K met for quantification of hepatic metabolic function. Total SUV of 18F-FDGal is a promising tool for quantification of metabolic liver function in pre-treatment evaluation of individual patients.

2-[(18)F]fluoro-2-deoxy-D-galactose PET/CT of hepatocellular carcinoma is not improved by co-administration of galactose.

INTRODUCTION: PET with [(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) is a promising imaging modality for detection of hepatocellular carcinoma (HCC). However, it can be difficult to distinguish small intrahepatic HCC lesions from surrounding liver tissue. Ut the competitive inhibition that galactose shows towards hepatic (18)F-FDGal metabolism, we tested the hypothesis that co-administration of galactose, at near-saturating doses, inhibits (18)F-FDGal metabolism to a greater extent in non-malignant hepatocytes than in HCC cells. This would increase the tumor to background ratio in the (18)F-FDGal PET scans with co-administration of galactose. METHODS: Three patients known to have HCC underwent two (18)F-FDGal PET/CT scans on consecutive days, one with and one without simultaneous constant intravenous infusion of galactose. On both days, (18)F-FDGal was injected in the beginning of a 45-min dynamic PET scan of the liver followed by a static PET scan from mid-thigh to the top of the skull starting 60-70min after (18)F-FDGal administration. Parametric images of the hepatic metabolic function expressed in terms of hepatic systemic clearance of (18)F-FDGal were generated from the dynamic PET recordings. RESULTS: Co-administration of galactose did not give significantly better discrimination of the HCC lesions from background. Parametric images of the hepatic metabolic function did not add additional useful information to the detection of HCC lesions compared to the static images of radioactivity concentrations. CONCLUSION: Co-administration of galactose did not improve the interpretation of the (18)F-FDGal PET/CT images and did not improve the detection of intrahepatic HCC lesions, either using static or parametric images.

Optimal 2-[(18)F]fluoro-2-deoxy-D-galactose PET/CT protocol for detection of hepatocellular carcinoma.

BACKGROUND: Positron emission tomography (PET) with the liver-specific galactose tracer 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) may improve diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to test which of three different (18)F-FDGal PET protocols gives the highest tumour-to-background (T/B) ratio on PET images and thus better detection of HCC tumours. METHODS: Ten patients with a total of 15 hepatic HCC tumours were enrolled prior to treatment. An experienced radiologist defined volumes of interest (VOIs) encircling HCC tumours on contrast-enhanced CT (ce-CT) images. Three PET/CT protocols were conducted following an intravenous (18)F-FDGal injection: (i) a 20-min dynamic PET/CT of the liver (to generate a 3D metabolic image), (ii) a traditional static whole-body PET/CT after 1 h, and (iii) a late static whole-body PET/CT after 2 or 3 h. PET images from each PET/CT protocol were fused with ce-CT images, and the average standardized uptake values (SUV) in tumour and background liver tissue were used to calculate (T/B) ratios. Furthermore, Tpeak/B ratios were calculated using the five hottest voxels in all hot tumours. The ratios for the three different PET protocols were compared. RESULTS: For the individual tumours, there was no significant difference in the T/B ratio between the three PET protocols. The metabolic image yielded higher Tpeak/B ratios than the two static images, but it was easier to identify tumours on the static images. One extrahepatic metastasis was detected. CONCLUSIONS: Neither metabolic images nor static whole-body images acquired 2 or 3 h after (18)F-FDGal injection offered an advantage to traditional whole-body PET/CT images acquired after 1 h for detection of HCC.

Combination of radiofrequency ablation with transarterial chemoembolization for treatment of hepatocellular carcinoma: experience from a Danish tertiary liver center.

BACKGROUND: Recent studies have shown that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) may offer a survival advantage compared to monotherapy. PURPOSE: To study the effectiveness of combination therapy with RFA and TACE compared to that of TACE alone in a Scandinavian tertiary liver cancer center. MATERIAL AND METHODS: A retrospective study of the patients treated with combination therapy vis-à-vis TACE alone from June 2007 to November 2012 was performed. Eighteen patients were treated with a combination of RFA and TACE with an interval of 1-4 days between the treatments. For comparison, a group of 18 patients treated with TACE as monotherapy in the same time period was matched with the combination group by demographic data, tumor characteristics, biochemical and clinical parameters, and performance status (PS). RESULTS: Each group consisted of 14 patients with cirrhosis and four without. There were no significant differences between the groups regarding age, gender, tumor characteristics, causes of cirrhosis, levels of bilirubin, creatinine, prothrombin time, Child Pugh score, or World Health Organization (WHO) performance status. The median survival of patients in the RFA + TACE combination group was 586 days compared to 296 days in the control group. The difference was not statistically significant (P = 0.26). However, when we stratified the data for cirrhosis and WHO performance status, patients in the combination group had significantly better survival (P = 0.024). CONCLUSION: Combination therapy with RFA and TACE for unresectable HCC, compared to TACE alone, may offer a survival benefit for a selected group of patients with HCC.