Dual-tracer PET/CT in the management of hepatocellular carcinoma

Abstract

Background & aims: Combined ¹⁸F-fluorodeoxyglucose (FDG) and ¹¹C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels.

Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed.

Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864).

Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

Keywords: Diagnosis; Hepatocellular Carcinoma; Imaging.

Graphical abstract

Fig. 1

Impact of dual-tracer PET/CT on identification of new lesions and modification of staging and treatment allocation (N = 559 scans in 524 patients).

Fig. 2

Modifications in tumor staging and treatment allocation using dual-tracer PET/CT. (A) Percentages of new lesions per patient, and modifications in tumor staging and treatment allocation using dual-tracer PET/CT according to baseline BCLC classification. (B) Representation of BCLC staging based on conventional imaging alone or conventional imaging with ¹⁸F-FDG PET/CT, or on conventional imaging with ¹¹C-acetate PET/CT or conventional imaging with dual-tracer PET/CT (percentages of each BCLC stage). BCLC, Barcelona Clinic Liver Cancer; FDG, fluorodeoxyglucose; PET/CT, positron-emission tomography/computed tomography.