title: ¹⁸F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma.
abstract: OBJECTIVE
  PET is a powerful tool for assessing targeted therapy. Since (18)F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated (18)F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial.
  
  
  METHODS
  Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUVmax, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods.
  
  
  RESULTS
  Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUVmax (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis.
  
  
  CONCLUSIONS
  (18)F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.
authors.affiliation: Nuclear Medicine Department, University Hospital, Brest, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Salaun
authors.forename: Loïc
authors.initials: L
authors.lastname: Campion
authors.forename: Catherine
authors.initials: C
authors.lastname: Ansquer
authors.forename: Eric
authors.initials: E
authors.lastname: Frampas
authors.forename: Cédric
authors.initials: C
authors.lastname: Mathieu
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.forename: Claire
authors.initials: C
authors.lastname: Bournaud
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vuillez
authors.forename: David
authors.initials: D
authors.lastname: Taieb
authors.forename: Caroline
authors.initials: C
authors.lastname: Rousseau
authors.forename: Delphine
authors.initials: D
authors.lastname: Drui
authors.forename: Eric
authors.initials: E
authors.lastname: Mirallié
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Chatal
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbet
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodéré
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018276:Carcinoma, Medullary / Q000000981:diagnostic imaging* / Q000532:radiotherapy / Q000556:secondary; D018278:Carcinoma, Neuroendocrine; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy / Q000556:secondary; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18