title: Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma.
abstract: BACKGROUND
  In patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT may be used to assess metabolic response. We investigated associations of metabolic response, mutational status, progression-free survival and overall survival in this population.
  
  
  METHODS
  Baseline and 4-week follow-up 18F-FDG-PET/CT were evaluated in 17 patients with metastatic melanoma and KIT amplifications and/or mutations treated with imatinib in a multicenter phase II clinical trial. The maximum standardized uptake values (SUVmax) were measured in up to 10 lesions on each scan. Metabolic response was classified using modified EORTC criteria. Each patient had a diagnostic CT or MR at baseline, after 6 weeks of therapy and then at intervals of 2 months and anatomic response was classified using RECIST 1.0. Median follow-up was 9.8 months.
  
  
  RESULTS
  Partial metabolic response (PMR), stable metabolic disease (SMD) and progressive metabolic disease (PMD) was seen in 5 (29%), 5 (29%), and 7 (41%) patients respectively. Five patients (29%) had a KIT mutation in exon 11, four of whom (80%) had PMR while 1 (20%) had SMD. Twelve patients (71%) did not have a KIT mutation in exon 11, and only 1 (8%) had PMR, 4 (33%) had SMD and 7 (58%) had PMD. There was agreement of metabolic and anatomic classification in 12 of 17 patients (71%). Four of 17 patients (24%) had PR on both metabolic and anatomic imaging and all had a KIT mutation in exon 11. Survival of patients with PMD was lower than with SMD or PMR.
  
  
  CONCLUSIONS
  Metabolic response by 18F-FDG-PET/CT is associated with mutational status in metastatic melanoma patients treated with imatinib. 18F-FDG-PET/CT may be a predictor of outcome, although a larger study is needed to verify this.
  
  
  BACKGROUND
  NCT00424515.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zukotynski
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Yap
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weber
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van den Abbeele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D005091:Exons; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit