Abstract
BackgroundAngiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC.MethodsThis prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously.ResultsSerum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p < 0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans, and kep, showed strong linear correlations (p < 0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p < 0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10− 3/min (p = 0.069), and kep > 900 10− 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival.ConclusionsThe present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.
Highlights
Angiogenesis assessment is important for personalized therapeutic intervention in patients with nonsmall-cell lung cancer (NSCLC)
Patients with initial higher values of angiogenesis-related magnetic resonance-positron emission tomography (MR-PET) parameters, including metabolic tumor volume (MTV) > 30 cm3 (p = 0.046), volume transfer constant (Ktrans) > 200 10− 3/min (p = 0.069), and kep > 900 10− 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which led to significantly longer overall survival
The present findings suggest that dynamic contrast-enhanced (DCE)-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC
Summary
Angiogenesis assessment is important for personalized therapeutic intervention in patients with nonsmall-cell lung cancer (NSCLC). Both PET and MRI bear potential for non-invasive assessment, and hybrid PET/MR imaging may be suitable for precise evaluation. DCEintegratedMR-PET combines the advantages of PET metabolic analysis and MRI permeability imaging for an integral evaluation and provides a powerful non-invasive imaging technology to assess tumor biology
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