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Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival

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Abstract

Since detailed knowledge regarding the pathophysiological properties—which in turn are responsible for differences in contrast enhancement—remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]) and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constantk 21) and standard parameters (maximum signal intensity (SI)-increase, [SI-I] over baseline and steepest SI-upslope, per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found betweenMVD and amplitudeA (P<0.01) andSI-I (P<0.05). No significant relationships were observed between theVEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based onk 21 and SI-U/s showed that tumors with highk 21 andSI-U/s values had a significantly (P<0.05, 0.001, respectively) worse disease outcome than tumors with lowk 21 andSI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI isMVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assessMVD or patient survival.

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Authors and Affiliations

  1. Department of Radiological Diagnostics and Therapy, German Cancer Research Center, Im Neuenheirner Feld 280, D-69120, Heidelberg, Germany

    Hans Hawighorst, Michael V. Knopp & Gerhard van Kaick

  2. Department of Obstetrics and Gynecology, University of Mainz, D-55101, Mainz, Germany

    Paul G. Knapstein

  3. Institute of Physiology and Pathophysiology, University of Mainz, D-55101, Mainz, Germany

    Peter Vaupel

Authors
  1. Hans Hawighorst
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  2. Paul G. Knapstein
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  3. Michael V. Knopp
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  4. Peter Vaupel
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  5. Gerhard van Kaick
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Correspondence to Hans Hawighorst.

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Hawighorst, H., Knapstein, P.G., Knopp, M.V. et al. Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival. MAGMA 8, 55–62 (1999). https://doi.org/10.1007/BF02590636

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  • DOI: https://doi.org/10.1007/BF02590636

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