title: Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI.
abstract: With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell lung cancer.
  
  
  METHODS
  Patients were evaluated using an imaging protocol including CT, 18F-FDG PET, H2(15)O PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS).
  
  
  RESULTS
  Forty-four patients were included, and 40 underwent CT and 18F-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P=0.01, and 12.5 vs. 2.9 mo, P=0.009, respectively). Whole-tumor Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values-that is, an increase in regions with low or high Ktrans values-after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P=0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P=0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and Ktrans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point.
  
  
  CONCLUSIONS
  PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, and Department of Biostatistics, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: de Langen
authors.forename: Vivian
authors.initials: V
authors.lastname: van den Boogaart
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Marcus
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Brans
authors.forename: Pieter
authors.initials: P
authors.lastname: Leffers
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy*; D003287:Contrast Media; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007089:Image Enhancement; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D019788:Fluorodeoxyglucose F18; D005947:Glucose