title: PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake.
abstract: OBJECTIVE
  Changes in tumor metabolism from positron emission tomography (PET) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NC) are predictive of pathologic response. Serial dynamic [(18)F]-FDG (fluorodeoxyglucose) PET scans were used to compare kinetic parameters with the standardized uptake value (SUV) as predictors of pathologic response, disease-free survival (DFS), and overall survival (OS).
  
  
  METHODS
  Seventy-five LABC patients underwent FDG PET prior to and at midpoint of NC. FDG delivery (K(1)), FDG flux (K(i)), and SUV measures were calculated and compared by clinical and pathologic tumor characteristics using regression methods and area under the receiver operating characteristic curve (AUC). Associations between K(1), K(i), and SUV and DFS and OS were evaluated using the Cox proportional hazards model.
  
  
  RESULTS
  Tumors that were hormone receptor negative, high grade, highly proliferative, or of ductal histology had higher FDG K(i) and SUV values; on an average, FDG K(1) did not differ systematically by tumor features. Predicting pathologic response in conjunction with estrogen receptor (ER) and axillary lymph node positivity, kinetic measures (AUC = 0.97) were more robust predictors than SUV (AUC = 0.84, P = 0.005). Changes in K(1) and K(i) predicted both DFS and OS, whereas changes in SUV predicted OS only. In multivariate modeling, only changes in K(1) remained an independent prognosticator of DFS and OS.
  
  
  CONCLUSIONS
  Kinetic measures of FDG PET for LABC patients treated with NC accurately measured treatment response and predicted outcome compared with static SUV measures, suggesting that kinetic analysis may hold advantage of static uptake measures for response assessment.
authors.affiliation: Division of Nuclear Medicine and Medical Oncology, University of Washington, Seattle, Washington 98109, USA. ldunnwal@u.washington.edu
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Dunnwald
authors.forename: Robert K
authors.initials: RK
authors.lastname: Doot
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Specht
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.forename: Georgiana K
authors.initials: GK
authors.lastname: Ellis
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Linden
authors.forename: Vijayakrishna K
authors.initials: VK
authors.lastname: Gadi
authors.forename: Brenda F
authors.initials: BF
authors.lastname: Kurland
authors.forename: Erin K
authors.initials: EK
authors.lastname: Schubert
authors.forename: Mark
authors.initials: M
authors.lastname: Muzi
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin