title: Monitoring metabolic response using FDG PET-CT during targeted therapy for metastatic colorectal cancer.
abstract: BACKGROUND
  The introduction of targeted drugs has had a significant impact on the approach to assessing tumour response. These drugs often induce a rapid cytostatic effect associated with a less pronounced and slower tumoural volume reduction, thereby impairing the correlation between the absence of tumour shrinkage and the patient's unlikelihood of benefit. The aim of the study was to assess the predictive value of early metabolic response (mR) evaluation after one cycle, and its interlesional heterogeneity to a later metabolic and morphological response assessment performed after three cycles in metastatic colorectal cancer (mCRC) patients treated with combined sorafenib and capecitabine.
  
  
  METHODS
  This substudy was performed within the framework of a wider prospective multicenter study on the predictive value of early FDG PET-CT response assessment (SoMore study). A lesion-based response analysis was performed, including all measurable lesions identified on the baseline PET. On a per-patient basis, a descriptive 4-class response categorization was applied based upon the presence and proportion of non-responding lesions. For dichotomic response comparison, all patients with at least one resistant lesion were classified as non-responding.
  
  
  RESULTS
  On baseline FDG PET-CT, 124 measurable "target" lesions were identified in 38 patients. Early mR assessments showed 18 patients (47 %) without treatment resistant lesions and 12 patients (32 %) with interlesional response heterogeneity. The NPV and PPV of early mR were 85 % (35/41) and 84 % (70/83), respectively, on a per-lesion basis and 95 % (19/20) and 72 % (13/18), respectively, on a dichotomized per-patient basis.
  
  
  CONCLUSIONS
  Early mR assessment performed after one cycle of sorafenib-capecitabine in mCRC is highly predictive of non-response at a standard response assessment time. The high NPV (95 %) of early mR could be useful as the basis for early treatment discontinuation or adaptation to spare patients from exposure to non-effective drugs.
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. erwin.woff@bordet.be.
authors.forename: Erwin
authors.initials: E
authors.lastname: Woff
authors.affiliation: Medical Oncology Department, Institut Jules Bordet, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Hendlisz
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.
authors.forename: Camilo
authors.initials: C
authors.lastname: Garcia
authors.affiliation: Medical Oncology Department, Institut Jules Bordet, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Amelie
authors.initials: A
authors.lastname: Deleporte
authors.affiliation: Oncology Department, Jolimont Hospital, Haine-St-Paul, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Delaunoit
authors.affiliation: Gastroenterology Medico-Surgical Department, Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Maréchal
authors.affiliation: Oncology Department, CHU Ambroise Paré, Mons, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Holbrechts
authors.affiliation: Oncology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van den Eynde
authors.affiliation: Gastroenterology Department, CHC Saint-Joseph, Liège, Belgium.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Demolin
authors.affiliation: Nuclear Medicine Department, Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Irina
authors.initials: I
authors.lastname: Vierasu
authors.affiliation: Nuclear Medicine Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lhommel
authors.affiliation: Nuclear Medicine Department, CHC Saint-Joseph, Liège, Belgium.
authors.forename: Namur
authors.initials: N
authors.lastname: Gauthier
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guiot
authors.affiliation: Data center Department, Institut Jules Bordet, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: Lieveke
authors.initials: L
authors.lastname: Ameye
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Flamen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D009536:Niacinamide; D000069287:Capecitabine; D000077157:Sorafenib
keywords: Early metabolic response assessment; FDG PET-CT; Metastatic colorectal cancer; Targeted therapy; Tumoral heterogeneity