title: (18)F-labelled fluorodeoxyglucose-positron emission tomography (FDG-PET) heterogeneity of response is prognostic in dabrafenib treated BRAF mutant metastatic melanoma.
abstract: BACKGROUND
  Little is known about the prevalence and clinical significance of heterogeneity of positron emission tomography with (18)F-labelled fluorodeoxyglucose-positron emission tomography (FDG-PET) response. We aim to determine the prevalence, and clinicopathologic correlates of intra-patient heterogeneity of FDG-PET response in metastatic melanoma treated with dabrafenib, and to determine whether heterogeneity predicts clinical outcome.
  
  
  METHODS
  Patients with BRAF mutant metastatic melanoma and ≥ 2 FDG avid lesions treated on the Phase I trial of dabrafenib at a single institution (n=23) were included. FDG-PET response was assessed by comparing baseline PET scans with scans at day 15. A heterogeneous response was defined as responding and new or metabolically progressing lesion(s) in a patient, or >10% of lesions with a stable metabolic response and responding lesions in a patient.
  
  
  RESULTS
  Six (26%) patients had a heterogeneous PET response. The median time to progression (TTP) was 7.4 months (95% confidence interval (CI): 6.5-8.3) for PET homogeneous responders and 3.0 months (95%CI: 0.6-5.4) for PET heterogeneous responders. There were no homogeneous non-responders. Age, BRAF mutation genotype, dose, and lactate dehydrogenase, did not predict for heterogeneity of PET response. Heterogeneity did not correlate with tumour response. Lung metastases were more likely to respond than other visceral metastatic sites.
  
  
  CONCLUSIONS
  Heterogeneous FDG-PET responses are common in metastatic melanoma treated with dabrafenib, and heterogeneity is associated with a shorter TTP. FDG-PET heterogeneity may predict molecular heterogeneity, and FDG-PET directed biopsies may facilitate investigation into mechanisms of resistance to signal pathway inhibitors.
authors.affiliation: Westmead Millennium Institute, The University of Sydney, Sydney, Australia. matteo.carlino@sydney.edu.au
authors.forename: Matteo S
authors.initials: MS
authors.lastname: Carlino
authors.forename: Catherine A B
authors.initials: CA
authors.lastname: Saunders
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Haydu
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.forename: C
authors.initials: C
authors.lastname: Martin Curtis
authors.forename: Peter F
authors.initials: PF
authors.lastname: Lebowitz
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D019275:Radiopharmaceuticals; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib