title: Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.
abstract: OBJECTIVE
  Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy.
  
  
  METHODS
  Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax.
  
  
  RESULTS
  The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002).
  
  
  CONCLUSIONS
  Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.
authors.affiliation: aDepartment of Radiology bDepartment of Medicine, Division of Medical Oncology, University of Colorado School of Medicine cDepartment of Biostatistics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado dThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Schmitt
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Kreidler
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Glueck
authors.forename: Rodabe N
authors.initials: RN
authors.lastname: Amaria
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Karl
authors.initials: K
authors.lastname: Lewis
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bagrosky
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Kwak
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Koo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D064847:Multimodal Imaging; D009154:Mutation; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D019788:Fluorodeoxyglucose F18; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases