Indicators of Lung Shunt Fraction Determined by Technetium-99 m Macroaggregated Albumin in Patients with Hepatocellular Carcinoma

Purpose: To determine the correlation of pre-procedural and imaging characteristics with lung shunt fraction (LSF) measured by technetium-99 m macroaggregated albumin (^99mTc-MAA) scan in patients with hepatocellular carcinoma. Methods: A retrospective study was conducted of 428 subjects with hepatocellular carcinoma from 2004 to 2011 assessed for lung shunting by ^99mTc-MAA scan. Baseline characteristics included age, gender, ethnicity, tumor burden, maximum dimension, number of lesions, presence of extrahepatic metastases, macrovascular (hepatic and portal vein) invasion, ascites on imaging, laboratory values, and alpha-fetoprotein (AFP). Univariate and multivariate logistic regression analysis was performed. Receiver operating characteristic curves were used to obtain sensitivity (SN), specificity (SP), and positive likelihood ratios (LR⁺) of characteristics for low LSF (LSF <10%) and high LSF (LSF >20%). Results: Statistically significant (p < 0.05) independent indicators of low LSF included bilirubin <1.45 mg/dL (SN = 49.5%, SP = 69.1%, LR⁺ = 1.60), maximum tumor size <7.15 cm (SN = 66.0%, SP = 75.9%, LR⁺ = 2.74), AFP ≤200 ng/mL (SN = 64.6%, SP = 65.0%, LR⁺ = 1.85), and absent macrovascular invasion (SN = 73.9%, SP = 64.9%, LR⁺ = 2.11). Independent indicators of high LSF included albumin <2.65 g/dL (SN = 64.3%, SP = 64.1%, LR⁺ = 1.79) and macrovascular invasion (SN = 74.4%, SP = 67.4%, LR⁺ = 2.28). A combined risk factor model was constructed. If there is no macrovascular invasion: LSF=e-3.846×(Bilirubin)0.303×AFP0.056×(Maximum dimension)0.364. With macrovascular invasion, LSF=e-3.629×(Bilirubin)0.303×AFP0.056×(Maximum dimension)0.364 (R² = 0.257). Since these factors all have LR⁺ between 2 and 5, they only reflect slight increase in LSF predictivity. Conclusion: Serum AFP, albumin, bilirubin, and portal/hepatic vein invasion on cross-sectional imaging are statistically significant but weak clinical indicators of LSF, as shown by low SN, SP, and LR⁺ for clinically relevant cutoff LSF values. Thus, these factors cannot be relied upon in clinical practice.