title: Therapy response assessment in metastatic melanoma patients treated with a BRAF inhibitor: adapted Choi criteria can reflect early therapy response better than does RECIST.
abstract: OBJECTIVE
  Targeted therapy can lead to considerable tumor reduction and may result initially in altered tissue at constant tumor size. In this setting, Response Evaluation Criteria in Solid Tumors (RECIST) can be inadequate for assessing early treatment response. Choi-criteria combine both size and density measurements. Our purpose was to evaluate computed tomography (CT) images of melanoma patients under BRAF-inhibitor therapy according to Choi-criteria which were adapted to our study (aChoi).
  
  
  METHODS
  Twelve patients (four male, eight female, mean age 49) with stage IV melanoma treated with a BRAF inhibitor were included. Response was assessed according to RECIST for 39 lesions in contrast-enhanced CT. Target volumes are semiautomatically segmented to calculate mean density for aChoi-criteria, thus using a two-dimensional nonstandardized region of interest could be prevented.
  
  
  RESULTS
  Eight patients are RECIST responders. aChoi-criteria indicate therapy response earlier compared to RECIST in five of eight patients. In seven cases, tumor density in CT had decreased 8 weeks after therapy start, whereas in some cases tumor size diminished less or even increased. Response according to aChoi was diagnosed in seven patients who showed in RECIST-evaluation stable disease in five and partial response in two cases. Fifteen weeks after therapy start almost all patients within the aChoi responders were RECIST responders, too. Only one aChoi responder showed still stable disease in RECIST.
  
  
  CONCLUSIONS
  Our initial data indicate that aChoi-criteria can reflect response to vemurafenib earlier compared to RECIST. This is of clinical significance as BRAF-inhibitors are cost-intensive targeted therapies and can cause severe side effects, so criteria for early therapy response have to be evaluated.
authors.affiliation: German Cancer Research Center (DKFZ) Heidelberg, Department of Radiology, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. m.uhrig@dkfz.de
authors.forename: Monika
authors.initials: M
authors.lastname: Uhrig
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schlemmer
authors.forename: Maria-Katharina
authors.initials: MK
authors.lastname: Ganten
mesh_terms: D000328:Adult; D000368:Aged; D003287:Contrast Media; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D055502:Secondary Prevention; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D013449:Sulfonamides / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D000077484:Vemurafenib
chemical_list: D003287:Contrast Media; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf