title: Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic studies of 5-fluorouracil.
abstract: Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.
authors.affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. h.vanlaarhoven@onco.umcn.nl
authors.forename: H W M
authors.initials: HW
authors.lastname: van Laarhoven
authors.forename: D W J
authors.initials: DW
authors.lastname: Klomp
authors.forename: M
authors.initials: M
authors.lastname: Rijpkema
authors.forename: Y L M
authors.initials: YL
authors.lastname: Kamm
authors.forename: D J Th
authors.initials: DJ
authors.lastname: Wagener
authors.forename: J O
authors.initials: JO
authors.lastname: Barentsz
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement; D008113:Liver Neoplasms / Q000556:secondary*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA; D005472:Fluorouracil