title: Multi-organ distant metastases confer worse disease-specific survival in differentiated thyroid cancer.
abstract: BACKGROUND
  Differentiated thyroid cancer (DTC) is usually associated with an excellent prognosis. With appropriate management of disease in the neck, death from thyroid cancer is more commonly related to the impact of distant metastases rather than locoregional recurrence. However, many patients with distant metastases can have very long periods of progression-free survival. The aims of this study were to determine the impact of single and multi-organ distant metastases (SODM and MODM) on survival, and identify factors that predict SODM progressing to MODM.
  
  
  METHODS
  An institutional database of 3664 previously untreated patients with DTC who had surgery between 1986 and 2010 was reviewed. One hundred and twenty-five (3.4%) patients developed distant metastases, of whom 93 developed SODM and 32 MODM. Overall survival was determined for each group by the Kaplan-Meier method. Factors predictive of MODM were identified by univariate and multivariate analysis. Multi-organ recurrence-free survival (MORFS) is a measure of SODM progressing to MODM disease. MORFS was calculated from the time of first distant metastasis to the time of second organ involvement by distant metastases.
  
  
  RESULTS
  The median age was 56 years (range 5-86 years). The median follow-up was 77 and 79 months (range 2-318 months) for the SODM and MODM groups respectively. SODM patients had five-year survival of 77.6% from the time of first distant metastasis, whereas MODM patients had a significantly poorer survival of just 15.3% from the time of second organ distant metastasis to death (p<0.001). The median time from first to second distant metastasis was 14.7 months (range 1-121 months). Seventy-one (57%) patients had M1 disease at presentation. Being aged ≥ 45 years (p = 0.05) and having an unstimulated serum thyroglobulin (Tg) level of ≥ 30 ng/mL at the time of diagnosis of initial distant metastasis (p<0.001) were univariate predictors of developing MODM. Controlling for age, an unstimulated serum Tg level of ≥ 30 ng/mL conferred a hazard ratio of 5.77 ([CI 2.13-15.64]; p = 0.001) for diagnosis of MODM.
  
  
  CONCLUSIONS
  MODM are associated with a poorer survival compared to patients with SODM. A serum Tg level >30 ng/mL at the time of first distant metastases confers more than a fivefold risk of having MODM identified during follow-up.
authors.affiliation: 1 Department of Surgery, Head and Neck Service, Memorial Sloan Kettering Cancer Center , New York, New York.
authors.forename: Laura Y
authors.initials: LY
authors.lastname: Wang
authors.forename: Frank L
authors.initials: FL
authors.lastname: Palmer
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Nixon
authors.forename: Dorothy
authors.initials: D
authors.lastname: Thomas
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.forename: Ian
authors.initials: I
authors.lastname: Ganly
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000401:mortality* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000401:mortality* / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000401:mortality* / Q000473:pathology; D055815:Young Adult