Early perfusion changes within 1 week of systemic treatment measured by dynamic contrast-enhanced MRI may predict survival in patients with advanced hepatocellular carcinoma
To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC).
Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan–Meier model and the double-sided log-rank test.
All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status.
Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC.
• DCE-MRI is helpful to evaluate perfusion changes of HCC after systemic treatment.
• Early perfusion changes within 1 week after treatment may predict overall survival.
• High Peak reduction was an independent favourable prognostic factor after systemic treatment.
KeywordsDCE-MRI Hepatocellular carcinoma Anti-angiogenic treatment Quantitative perfusion MRI Image biomarker
The scientific guarantor of this publication is Tiffany Ting-Fang Shih. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This study has received funding by National Taiwan University Hospital (grant number NTUH. 101-001863); and the Ministry of Science and Technology, Executive Yuan, ROC, Taiwan (grant number NSC 100-2314-B-002-053). One of the authors has significant statistical expertise. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Some study subjects or cohorts have been previously reported. All patients included in this study were associated with two other trials (Study 1— 54 patients in a phase II clinical trial using vandetanib, registered with ClinicalTrials.gov NCT00508001; Study 2—38 patients in a phase II clinical trial using sorafenib and tegafur/uracil, registered with ClinicalTrials.gov NCT00464919) conducted by our group.
In Study 1 with vandetanib, the previously published article  found that Ktrans did not differ significantly between the three treatment groups (group 1, vandetanib 300 mg/day; group 2, vandetanib 100 mg/day; group 3, placebo). Vascular response, defined as a greater than 30% reduction of Ktrans values from baseline after 7 days of study drug treatment, was not significantly different between the groups either. The follow-up duration was 12 months.
In Study 2 with sorafenib and tegafur/uracil, the previously published article  found that a vascular response, defined as a greater than 40% reduction of Ktrans values from baseline after 14 days of study drug treatment, correlated with longer progression-free survival and overall survival. Percentage of Ktrans change after treatment was an independent predictor of tumour response, progression-free survival, and overall survival. The follow-up duration was 140 months.
The association of baseline DCE-MRI parameters before treatment with overall survival outcome in these patients has been reported in our previous study . The current study investigated the association of changes in six DCE-MRI parameters within 1 week following treatment with overall survival in these patients. The results of the current study have not been published previously.
Methodology: retrospective, diagnostic or prognostic study, performed at one institution.
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