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 mm2/sec to 1.60×10−3 mm2/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.

Open-Label Single-Arm Phase II Trial of Sorafenib Therapy with Drug-eluting Bead Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Clinical Results

“…In our study, among patients who were assessable for radiologic response (n = 33) at 6-month follow-up, the overall disease control rate, which was based on both RECIST and EASL criteria, was 94%, a clearly encouraging result. In addition, median tumor enhancement changed from 80% at baseline to 15% at 6 months (20). These data strongly suggest that the combination of DEB TACE and sorafenib therapy was effective in decreasing intrahepatic tumor burden and, in turn, controlling disease progression in the liver.…”

Interreader and inter-test agreement in assessing treatment response following transarterial embolization for hepatocellular carcinoma

“…In some studies investigators have estimated the percent change in tumour enhancement visually, as is often done in clinical practice [14, 15]; however, in other studies, the enhancing tissue has been measured uni- [16] or bidimensionally [11, 17] or by using a volumetric approach [18–21]. Furthermore, in all of these studies, the magnitude of response was decided in consensus without analyzing interreader agreement.…”

Quantitative volumetric functional MR imaging: an imaging biomarker of early treatment response in hypo-vascular liver metastasis patients after yttrium-90 transarterial radioembolization

“…Tumor necrosis after TARE occurs centrally, and therefore, 3D assessment is more representative of the changes that occur globally within a targeted lesion. Furthermore, the software enabled easy and better reproducibility analysis of multiparametric MR imaging data compared to ROI-based axial measurements [15,24,28]. The presented data by Chapiro et al [29] provided multilayer proof of the precision of 3D quantitative perfusion and diffusion-weighted MR imaging when correlated with pathologic examination as a standard of Ref.…”

“…While tumor shrinkage may not be initially apparent, there were changes in tumor ADC and enhancement that could be valuable in assessing early therapeutic efficacy [21][22][23]. Previous studies [4,15,24] demonstrated the promising role of quantitative volumetric functional MRI to detect early tumor response to LRT of liver malignancies. Changes in volumetric functional MR metrics may precede conventional tumor size changes, potentially overcoming the limitations of mRECIST and EASL.…”