title: A Phase II Study of 3'-Deoxy-3'-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688.
abstract: Our objective was to determine whether early change in standardized uptake values (SUVs) of 3'deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC.
  
  
  METHODS
  This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent (18)F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed.
  
  
  RESULTS
  Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31-46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50-0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001).
  
  
  CONCLUSIONS
  (18)F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy (18)F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of (18)F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test (18)F-FLT PET in a more uniformly treated patient population.
authors.affiliation: Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Lale
authors.initials: L
authors.lastname: Kostakoglu
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Fenghai
authors.initials: F
authors.lastname: Duan
authors.affiliation: Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.affiliation: Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Jolles
authors.affiliation: Virginia Commonwealth University, Richmond, Virginia Massey Cancer Center of Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Mark
authors.initials: M
authors.lastname: Muzi
authors.affiliation: Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
authors.forename: Jean
authors.initials: J
authors.lastname: Cormack
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: John P
authors.initials: JP
authors.lastname: Muzi
authors.affiliation: Abramson Cancer Center and Perelman School of Medicine University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pryma
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Specht
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Linda
authors.initials: L
authors.lastname: Hovanessian-Larsen
authors.affiliation: Morton Mease Plant Hospital, Clearwater, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Miliziano
authors.affiliation: American College of Radiology Imaging Network (ACRIN), Philadelphia, Pennsylvania; and.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mallett
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Shields
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
mesh_terms: D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D015224:Dideoxynucleosides / Q000009:adverse effects; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019394:Ki-67 Antigen; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; C002854:alovudine
keywords: 18F-FLT PET; breast cancer; early treatment response; neoadjuvant therapy