Elsevier

Magnetic Resonance Imaging

Volume 62, October 2019, Pages 78-86
Magnetic Resonance Imaging

Original contribution
Dynamic contrast-enhanced MRI to assess hepatocellular carcinoma response to Transarterial chemoembolization using LI-RADS criteria: A pilot study

https://doi.org/10.1016/j.mri.2019.06.017Get rights and content

Abstract

Purpose

To identify quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters indicating tumor response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE).

Materials and methods

This prospective pilot study was approved by our institutional review board; written and informed consent was obtained for each participant. Patients underwent DCE-MRI examinations before and after TACE. A variable flip-angle unenhanced 3D mDixon sequence was performed for T1 mapping. A dynamic 4D mDixon sequence was performed after contrast injection for assessing dynamic signal enhancement. Nonparametric analysis was conducted on the time-intensity curves. Parametric analysis was performed on the time-concentration curves using a dual-input single-compartment model. Treatment response according to Liver Reporting and Data System (LI-RADS) v2018 was used as the reference standard. The comparisons within groups (before vs. after treatment) and between groups (nonviable vs. equivocal or viable tumor) were performed using nonparametric bootstrap taking into account the clustering effect of lesions in patients.

Results

Twenty-eight patients with 52 HCCs (size: 10–104 mm) were evaluated. For nonviable tumors (n = 27), time to peak increased from 62.5 ± 18.2 s before to 83.3 ± 12.8 s after treatment (P< 0.01). For equivocal or viable tumors (n = 25), time to peak and mean transit time significantly increased (from 54.4 ± 24.1 s to 69.5 ± 18.9 s, P < 0.01 and from 14.2 ± 11.8 s to 33.9 ± 36.8 s, P= 0.01, respectively) and the transfer constant from the extracellular and extravascular space to the central vein significantly decreased from 14.8 ± 14.1 to 8.1 ± 9.1 s−1 after treatment (P= 0.01).

Conclusion

This prospective pilot DCE-MRI study showed that time to peak significantly changed after TACE treatment for both groups (nonviable tumors and equivocal or viable tumors). In our cohort, several perfusion parameters may provide an objective marker for differentiation of treatment response after TACE in HCC patients.

Introduction

Hepatocellular carcinoma (HCC) is responsible for 11% of all cancer-related deaths and ranks as the second leading cause of cancer mortality worldwide. In North America, HCC incidence and mortality rates are increasing [1]. Transarterial chemoembolization (TACE) is generally used with palliative intent or as a bridge to transplantation for non-metastatic HCC with T2 or T3 stage disease and no vascular involvement in patients who are not candidates for resection, ablation or transplantation [2,3].

HCCs are hypervascular tumors associated with a typical enhancement pattern observed on diagnostic imaging [4,5]. The growth and progression of such tumors are the result of changes in intranodular blood supply characterized by high arterial flow due to angiogenesis leading to unpaired neoarteries in the portal triad [6]. The Liver Imaging Reporting and Data System (LI-RADS) describes five major imaging features for the diagnosis of HCC on contrast-enhanced CT or MRI [5]. Of those, two imaging features refer to transient vascular phenomena observed on dynamic contrast-enhanced imaging: nonrim arterial phase hyperenhancement and nonperipheral “washout” during the portal venous and equilibrium phases (Fig. 1). Although there is an attempt to standardize interpretation of liver imaging, assessment of viable HCC and treatment response using such qualitative imaging characteristics remains subjective [5].

Furthermore, the accepted standard in assessing treatment response in HCC, the modified Response Evaluation Criteria in Solid Tumor (mRECIST), is based on contrast-enhanced CT or MRI acquired every 6–8 weeks after treatment [7], and relies on global patient-level assessment of changes in tumor size which usually occur 6–12 months after treatment [8]. However, an early lesion-level assessment of treatment response according to the LI-RADS v2018 Treatment Response algorithm, which takes into account the variable appearances of tumor after therapy for each lesion, is essential in planning additional therapy and can benefit patient outcome [8,9]. The LI-RADS Treatment Response algorithm, which incorporates concepts from mRECIST and European Association for the Study of the Liver (EASL) systems, relies on subjective visual assessment. DCE-MRI may provide objective and quantitative criteria to assess treatment response and differentiate nonviable from viable tumors in a shorter time period [10], as it offers a dynamic component to the evaluation of the viability of liver tumors which are not present in the standardized measurement.

The traditional approach for the diagnosis and assessment of treatment response of HCC has been to perform MRI with high spatial resolution, but low temporal resolution (i.e. 4–5 time points spaced 30–120 s apart). However, this approach relies on detection and qualitative analysis of residual vascularized portions of active HCC tumors. Another important concern with standard 3-phased MRI is that the arterial hepatic phase may overlap with portal venous enhancement due to the low temporal resolution. More recently, dynamic contrast-enhanced (DCE)-MRI providing higher temporal resolution with a minor trade-off in spatial resolution has been proposed to address this issue as it provides multiple arterial and venous phases [11]. Previous studies have shown that DCE-MRI can be used to derive objective quantitative metrics of viable HCC tumor using pharmacokinetic models that can supplement the subjective qualitative interpretation by radiologists, with minimal disruptions to clinical workflow [[12], [13], [14]]. This quantitative imaging technique, which measures changes in signal intensity due to local perfusion after injection of a gadolinium-based contrast agent, permits nonparametric and parametric analysis of tumor perfusion relative to background liver [15].

Recent DCE-MRI literature has assessed the efficacy of non-invasive evaluation of hepatic perfusion parameters. These studies either assessed DCE-MRI parameters in a cross-sectional [13,14] or longitudinal [8,16,17] approach by evaluating TACE only [13], TACE in combination with sunitinib [16], or sorafenib [17]. Most studies were prospective [13,14,16,17] and only a number of studies enrolled patients retrospectively [8,18]. These studies assessed tumor size [8] in addition to parametric [13,19], and non-parametric [8] analyses of tumor perfusion relative to background liver. We hypothesize that DCE-MRI parameters may provide objective quantitative biomarkers of HCC tumor response after TACE.

The purpose of this pilot study was to identify quantitative DCE-MRI perfusion parameters indicating tumor response of HCC to TACE. After performing a comprehensive literature review, we have integrated most DCE-MRI parameters reported in the literature for assessment of tumor response.

Section snippets

Patients

This single-site prospective clinical trial (ClinicalTrials.gov reference number: NCT02878109) was approved by our institutional review board. All patients provided written and informed consent before participating in the study.

Patients diagnosed by imaging with LI-RADS criteria demonstrating at least one tumor that is probably or definitely HCC (LR-4 or LR-5) and scheduled for TACE (targeted or segmental) treatment between June 2016 and June 2018 according to clinical indications were eligible

Characteristics of patients and tumors

Twenty-eight patients totaling 52 HCCs with size ranging from 10 to 104 mm were included in this pilot study. The flowchart of patient selection is shown in Fig. 4 and characteristics of patients and tumors in Table 2. Individuals diagnosed with HCC and awaiting TACE treatment between June 2016 and June 2018 were eligible for this study (n = 152). Of those, 119 patients were excluded. The three most common reasons for patient exclusion were related to MRI, refusal, and distance from hospital.

Discussion

This prospective clinical study identified quantitative DCE-MRI perfusion parameters for assessing tumor response of HCC to TACE. All patients had at least one malignant tumor (probably or definitely HCC) confirmed by previous diagnostic imaging and were scheduled for TACE treatment. MRI examinations were interpreted independently and in consensus by radiologists to determine individual tumor response according to LI-RADS v2018 treatment response criteria.

Of note, the interreader agreement for

Institution from which the work originated

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM).

900, rue Saint-Denis (Tour Viger).

Montreal, Qc, Canada, H5B 1B2.

Presentation

An earlier version of this work was presented at:

ISMRM 2018, Paris, France. Poster. #2623

Dynamic Contrast-Enhanced MRI to Assess Hepatocellular Carcinoma Response to Transarterial Chemoembolization: a Pilot Study.

Thibodeau-Antonacci A, Petitclerc L, Gilbert G, Bilodeau L, Castel H, Turcotte S, Olivié D, Huet C, Perreault P, Soulez P, Tang A, Kadoury S.

Presentation

This paper was not presented at a previous meeting or submitted for presentation at a future meeting.

Funding

This work was funded by an Operating Grant from the Canadian Institutes of Health Research (CIHR) (#340909) to Samuel Kadoury (PI), a Clinical Research Scholarship – Junior 1 Salary Award from the Fonds de Recherche du Québec - Santé (FRQS-ARQ) to Simon Turcotte and a Junior 2 Salary Award from the Fonds de recherche du Québec - Santé and the Fondation de l'association des Radiologists du Québec (FRQS-ARQ #34939) to An Tang.

Acknowledgments

N/A.

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