title: Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor.
abstract: OBJECTIVE
  Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure.
  
  
  METHODS
  Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  
  
  RESULTS
  Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes.
  
  
  CONCLUSIONS
  Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.
authors.affiliation: Nuclear Medicine Department,Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland John.Prior@chuv.ch
authors.forename: John O
authors.initials: JO
authors.lastname: Prior
authors.forename: Michael
authors.initials: M
authors.lastname: Montemurro
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Orcurto
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: François
authors.initials: F
authors.lastname: Luthi
authors.forename: Jean
authors.initials: J
authors.lastname: Benhattar
authors.forename: Louis
authors.initials: L
authors.lastname: Guillou
authors.forename: Valérie
authors.initials: V
authors.lastname: Elsig
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Angelika Bischof
authors.initials: AB
authors.lastname: Delaloye
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D019788:Fluorodeoxyglucose F18; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D016879:Salvage Therapy; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D019788:Fluorodeoxyglucose F18; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000077210:Sunitinib