Abstract
BackgroundHypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC).Materials and methodsThirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (Ktrans) and a rate constant from EES to plasma (Kep), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal–Wallis, Mann–Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1α expression.ResultsPharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF-1α expression (Ktrans L-ROI P = 0.021; Ktrans S-ROI P = 0.018 and Kep L-ROI P = 0.032; Kep S-ROI P = 0.033). Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-ROI; 0.840 Ktrans S-ROI; 0.808 Kep L-ROI and 0.808 Kep L-ROI).ConclusionThis preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1α in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation.
Highlights
Ovarian cancer (OC) is one of the most lethal malignancies in women
Pharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF1α expression
Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-regions of interest (ROIs); 0.840 Ktrans small circle ROI (S-ROI); 0.808 Kep large ROI (L-ROI) and 0.808 Kep L-ROI). This preliminary study demonstrated that pharmacokinetic dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) perfusion parameters are associated with the hypoxia specific marker, HIF-1α in ovarian cancer (OC)
Summary
Ovarian cancer (OC) is one of the most lethal malignancies in women. the mortality rate has declined by 33% between 1976 and 2015 with reductions in both incidence and mortality, the five-year survival rate is as low as 47% [1]. Tumor hypoxia is a novel, potentially useful, target for anti-cancer drugs [2,3,4,5,6]. OC is sensitive to chemotherapy, 70% of patients relapse [13] This has led to studies investigating which kind of combinations of drugs or other treatment modalities would benefit patients more. Hypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC)
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