title: Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma.
abstract: OBJECTIVE
  Distant metastasis has a negative impact on survival in differentiated thyroid carcinoma (DTC). The timing of this manifestation, however, is of unknown prognostic relevance. The aim of this retrospective study was to investigate the potential significance of discriminating synchronous versus metachronous distant metastases (SDM vs. MDM) for the outcome of patients with DTC.
  
  
  METHODS
  We retrospectively analyzed a consecutive cohort of n = 89 patients with distant metastases of DTC (43 with follicular, 46 with papillary DTC histology; mean age 52.6 ± 17.7 years) undergoing radioiodine treatment at our institution. All patients were treated with the same protocol consisting of ablative radioiodine therapy (RIT, 3.7 GBq) and one post-ablation treatment after 3 months (3.7-11.1 GBq). Further cycles of RIT were administered for recurrent, progressive or newly developed metastatic disease. We distinguished 2 types of distant metastases according to the time of manifestation: SDM (within ≤12 months after DTC diagnosis) and MDM (occurring >12 months after diagnosis). Tumor-related survival was analyzed using the Kaplan-Meier method. Uni- and multivariate analyses including the Cox proportional hazards model were performed with a significance level of p < 0.05.
  
  
  RESULTS
  The mean follow-up period was 13.8 ± 1.2 years. SDM were present in 49 (55.1 %), MDM in 40 (44.9 %) patients. MDM were associated with shorter tumor-related survival (p = 0.002). 5-year and 10-year survival rates were 68.5 % and 34.8 % for MDM, and 84.3 % and 66.9 % for SDM, respectively. Within both age subgroups of <45 and ≥45 years, SDM were also linked with longer survival. No effect on tumor-related survival was found for the co-variables sex, lymph node metastases and histologic type.
  
  
  CONCLUSIONS
  Distinguishing synchronous from metachronous manifestation of distant metastases may add an important prognostic feature to risk stratification in DTC, as proven metachronous appearance is associated with impaired survival.
authors.affiliation: Department of Nuclear Medicine, University Duisburg-Essen, Essen, Germany.|Department of Nuclear Medicine, Saarland University Hospital, Kirrbergerstr., Geb. 50, D-66421, Homburg, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Sabet
authors.affiliation: Department of Nuclear Medicine, University Duisburg-Essen, Essen, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Binse
authors.affiliation: Department of Nuclear Medicine, University Hospital, Bonn, Germany.
authors.forename: Semih
authors.initials: S
authors.lastname: Dogan
authors.affiliation: Department of Nuclear Medicine, University Duisburg-Essen, Essen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Nuclear Medicine, University Duisburg-Essen, Essen, Germany.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Rosenbaum-Krumme
authors.affiliation: Department of Nuclear Medicine, University Hospital, Bonn, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Biersack
authors.affiliation: Department of Nuclear Medicine, University Hospital, Bonn, Germany.|Department of Radiology and Nuclear Medicine, Confessional Hospital "Barmherzige Brüder", Trier, Germany.
authors.forename: Kim
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Nuclear Medicine, Saarland University Hospital, Kirrbergerstr., Geb. 50, D-66421, Homburg, Germany. samer.ezziddin@uks.eu.|Department of Nuclear Medicine, University Hospital, Bonn, Germany. samer.ezziddin@uks.eu.
authors.forename: Samer
authors.identifier: http://orcid.org/0000-0003-4110-3375
authors.initials: S
authors.lastname: Ezziddin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000401:mortality* / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000401:mortality* / Q000517:prevention & control*; D015995:Prevalence; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals
keywords: Differentiated thyroid cancer; Distant metastases; Radioiodine therapy; Risk stratification