Volumetric assessment of tumour response using functional MR imaging in patients with hepatocellular carcinoma treated with a combination of doxorubicin-eluting beads and sorafenib

Abstract

Objective: To prospectively assess treatment response using volumetric functional magnetic resonance imaging (MRI) metrics in patients with hepatocellular carcinoma (HCC) treated with the combination of doxorubicin-eluting bead-transarterial chemoembolization (DEB TACE) and sorafenib.

Methods: A single center study enrolled 41 patients treated with systemic sorafenib, 400 mg twice a day, combined with DEB TACE. All patients had a pre-treatment and 3-4 week post-treatment MRI. Anatomic response criteria (RECIST, mRECIST and EASL) and volumetric functional response (ADC, enhancement) were assessed. Statistical analyses included paired Student's t-test, Kaplan-Meier curves, Cohen's Kappa, and multivariate cox proportional hazard model.

Results: Median tumour size by RECIST remained unchanged post-treatment (8.3 ± 4.1 cm vs. 8.1 ± 4.3 cm, p = 0.44). There was no significant survival difference for early response by RECIST (p = 0.93). EASL and mRECIST could not be analyzed in 12 patients. Volumetric ADC increased significantly (1.32 × 10(-3) mm(2)/sec to 1.60 × 10(-3) mm(2)/sec, p < 0.001), and volumetric enhancement decreased significantly in HAP (38.2% to 17.6%, p < 0.001) and PVP (76.6% to 41.2%, p < 0.005). Patients who demonstrated ≥ 65% decrease PVP enhancement had significantly improved overall survival compared to non-responders (p < 0.005).

Conclusion: Volumetric PVP enhancement was demonstrated to be significantly correlated with survival in the combination of DEB TACE and sorafenib for patients with HCC, enabling precise stratification of responders and non-responders.

Key points: • PVP enhancement is significantly correlated with survival in responders (p < 0.005). • There was no significant survival difference for early response using RECIST (p = 0.93). • mRECIST or EASL could not assess tumour response in 29% of patients.

Fig. 1

Inclusion and exclusion criteria in our patient population

Fig. 2

Hepatocellular carcinoma pretreatment and post-treatment showing volumetric change by PVP. Hepatocellular carcinoma (a) at baseline showed a tumour volume of 294.3 cm³, while (b) Post-treatment tumour volume was 266.6 cm³. The lesion showed no change by RECIST. c Volumetric ADC map showed no change in mean volumetric ADC from 1.23×10⁻³ mm²/sec before treatment to 1.35× 10⁻³ mm²/sec after treatment, as depicted in the histogram (blue: pretreatment, orange: post-treatment). d Enhancement in HAP decreased from 24.7 % to 2.2 % post-treatment, as depicted in the histogram (blue: pretreatment, orange: post-treatment). e Histogram depicts that enhancement in PVP decreased from 73.6 % to 24.3 %, with a 66 % decrease early post-treatment (blue: pretreatment, orange: post-treatment). There is a leftward shift in the blended histogram representing decreasing enhancement post-treatment and indicating favorable response to therapy

Fig. 3

Hepatocellular carcinoma assessed pretreatment and post-treatment by volumetric functional MRI. Hepatocellular carcinoma (a) at baseline showed a tumour volume of 333.8 cm³, while (b) Post treatment tumour volume was 255.8 cm³. c Volumetric ADC map showed volumetric mean ADC change from 1.64×10⁻³ mm²/sec to 1.55×10⁻³ mm²/sec as depicted in the histogram (blue: pretreatment, orange: post-treatment). d Enhancement in HAP increased from 1.33 % to 46.9 % post-treatment, as depicted in the histogram (blue: pretreatment, orange: post-treatment). e Enhancement in PVP increased from 73.9 % to 100 % after treatment, as depicted in the histogram (blue: pretreatment, orange: post-treatment)

Fig. 4

Survival in months, stratified by RECIST, volumetric ADC and enhancement in arterial phase in responders and non-responder 3–4 weeks after treatment. a The blue curve represents responders by RECIST (n=2, median survival of 502 days) and the green curve represents non-responders by RECIST (n=39, median survival of 563 days) 3–4 weeks post-treatment with combination DEB TACE and Sorafenib. [log rank p= 0.93]. b The blue curve represents responders (≥25 % decrease in ADC, n=11, median survival of 563 days) and the green curve represents non-responders (<25 % decrease or increase in ADC, n=23, median survival of 686 days) 3–4 weeks post-treatment with combination DEB TACE and Sorafenib [log rank p=0.71]. c The blue curve represents responders (≥50 % decrease in HAP, n=22, median survival of 631 days) and the green curve represents non-responders (<50 % decrease or increase in HAP, n=19, median survival of 404 days) 3–4 weeks post-treatment with combination DEB TACE and Sorafenib [log rank p=0.58]

Fig. 5

Survival in months stratified by volumetric enhancement in portal venous phase, stratifying responders from non-responder 3–4 weeks after treatment. The blue curve represents responders (≥65 % decrease in PVP, n=19, median survival of 823 days) and the green curve represents non-responders (<65 % decrease or increase in PVP, n=22, median survival of 372 days) 3–4 weeks post-treatment with combination DEB TACE and Sorafenib [log rank p<0.005]