Diffuse infiltrative hepatocellular carcinoma: assessment of presentation, treatment, and outcomes

Abstract

Background: Data on infiltrating hepatocellular carcinoma (HCC) are limited. We sought to define treatment and outcome of patients treated with infiltrating HCC compared with patients who had advanced multifocal HCC.

Methods: Between January 2000 and July 2011, a total of 147 patients with advanced HCC were identified from the Johns Hopkins Hospital database (infiltrative, n = 75; multifocal, n = 72). Clinicopathologic data were compared by HCC subtype.

Results: Patients with infiltrating HCC had higher alfa-fetoprotein levels (median infiltrative, 326.5 ng/mL vs. multifocal, 27.0 ng/mL) and larger tumors (median size, infiltrating, 9.2 cm vs. multifocal, 5.5 cm) (P < 0.05). Imaging failed to reveal a discrete lesion in 42.7 % of patients with infiltrating HCC. Most infiltrating HCC lesions presented as hypointense on T1-weighted images (55.7 %) and hyperintense on T2-weighted images (80.3 %). Among patients with infiltrating HCC, most (64.0 %) were treated with intra-arterial therapy (IAT), and periprocedural morality was 2.7 %. Patients treated with IAT had longer survival versus patients receiving best support care (median survival, IAT, 12 months vs. best supportive care, 3 months; P = 0.001). Survival after IAT was similar among patients treated with infiltrating HCC versus multifocal HCC (hazard ratio 1.29, 95 % confidence interval 0.82-2.03; P = 0.27). Among infiltrating HCC patients, pretreatment bilirubin >2 mg/dL and alfa-fetoprotein >400 ng/mL were associated with worse survival after IAT (P < 0.05). Patients with progressive disease after IAT had higher risk of death versus patients who had stable/responsive disease (hazard ratio 3.53, 95 % confidence interval 1.49-8.37; P = 0.004).

Conclusions: Patients with infiltrative HCC often present without a discrete lesion on imaging. IAT for infiltrative HCC was safe and was associated with survival comparable to IAT outcomes for patients with multifocal HCC. Infiltrative HCC morphology is not a contraindication to IAT therapy in select patients.

FIG. 1

A Extensive infiltrative T1-weighted hypointense (a), T2-weighted with fat saturation hyperintense (b) mass (M). Heterogeneously enhancing in arterial phase (c) with washout on portal phase (d) involving right more than left hepatic lobe, on delayed images (e) shows extensive tumor thrombus in the portal vein (*) compatible with infiltrating HCC. B A 75-year-old woman with infiltrative HCC. Before treatment (a–e), there is a mass (M) of 12.6 × 8.5 cm hypointense in T1-weighed (a) heterogeneously hyperintense in T2-weighted (b) images. The mass shows diffusion restriction with apparent diffusion coefficient (ADC) value of 1.03 × 10⁻³ mm²/s (d). After contrast administration, there is enhancement in arterial phase (d) with washout on delayed images (e). The patient underwent IAT (f–j); the lesion persisted as hypointense in T1-weighted (f) and heterogeneously hyperintense in T2-weighted (g) images. The mass decreased in size to 10 × 6.8 cm, showing increase in ADC (h) value 1.77 × 10⁻³ mm²/s, decreased enhancement (arrows) in arterial phase (i), and increased necrotic areas in delayed images (j) consistent with partial response. C Sixty-seven-year-old man with a history of infiltrative cryptogenic HCC. Axial images show a large lesion (arrows) measuring 16 × 11 cm with innumerable smaller lesions hypointense on T1-weighted (a) heterogeneously hyperintense on T2-weighted (b) images. After contrast administration, arterial phase (c) demonstrated uptake of contrast within the mass with washout on portal phase (d). After IAT treatment, the mass increased in size (16 × 14 cm) with persistent hypointense in T1-weighted (e) heterogeneously hyperintense on T2-weighted (f) images. Postcontrast images showed avid enhancement in hepatic arterial phase (g) with washout on portal venous phase (h). All other lesions (arrowheads) are overall increased in size, compatible with progressive disease

FIG. 1

A Extensive infiltrative T1-weighted hypointense (a), T2-weighted with fat saturation hyperintense (b) mass (M). Heterogeneously enhancing in arterial phase (c) with washout on portal phase (d) involving right more than left hepatic lobe, on delayed images (e) shows extensive tumor thrombus in the portal vein (*) compatible with infiltrating HCC. B A 75-year-old woman with infiltrative HCC. Before treatment (a–e), there is a mass (M) of 12.6 × 8.5 cm hypointense in T1-weighed (a) heterogeneously hyperintense in T2-weighted (b) images. The mass shows diffusion restriction with apparent diffusion coefficient (ADC) value of 1.03 × 10⁻³ mm²/s (d). After contrast administration, there is enhancement in arterial phase (d) with washout on delayed images (e). The patient underwent IAT (f–j); the lesion persisted as hypointense in T1-weighted (f) and heterogeneously hyperintense in T2-weighted (g) images. The mass decreased in size to 10 × 6.8 cm, showing increase in ADC (h) value 1.77 × 10⁻³ mm²/s, decreased enhancement (arrows) in arterial phase (i), and increased necrotic areas in delayed images (j) consistent with partial response. C Sixty-seven-year-old man with a history of infiltrative cryptogenic HCC. Axial images show a large lesion (arrows) measuring 16 × 11 cm with innumerable smaller lesions hypointense on T1-weighted (a) heterogeneously hyperintense on T2-weighted (b) images. After contrast administration, arterial phase (c) demonstrated uptake of contrast within the mass with washout on portal phase (d). After IAT treatment, the mass increased in size (16 × 14 cm) with persistent hypointense in T1-weighted (e) heterogeneously hyperintense on T2-weighted (f) images. Postcontrast images showed avid enhancement in hepatic arterial phase (g) with washout on portal venous phase (h). All other lesions (arrowheads) are overall increased in size, compatible with progressive disease

FIG. 2

Overall survival among patients with infiltrating HCC. Survival is stratified by receipt of IAT versus best supportive care (P < 0.001)

FIG. 3

Overall survival after IAT stratified by EASL response. Patients who had progressive disease after IAT had a survival of only 2 months compared with 12 months for patients who had stable or responsive disease (P = 0.001)