title: Bimodal mortality dynamics for uveal melanoma: a cue for metastasis development traits?
abstract: BACKGROUND
  The study estimates mortality dynamics (event-specific hazard rates over a follow-up time interval) for uveal melanoma.
  
  
  METHODS
  Three thousands six hundred seventy two patients undergoing radical or conservative treatment for unilateral uveal melanoma, whose yearly follow-up data were reported in three published datasets, were analysed. Mortality dynamics was studied by estimating with the life-table method the discrete hazard rate for death. Smoothed curves were obtained by a Kernel-like smoothing procedure and a piecewise exponential regression model. The ratio deaths/patients at risk per year was the main outcome measure.
  
  
  RESULTS
  The three explored hazard rate curves display a common bimodal pattern, with a sudden increase peaking at about three years, followed by reduction until the sixth-seventh year and a second surge peaking at about nine years after treatment.
  
  
  CONCLUSIONS
  The bimodal pattern of mortality indicates that uveal melanoma metastatic development cannot be explained by a continuous growth model. Similar metastasis dynamics have been reported for other tumours, including early breast cancer, for which it supported a paradigm shift to an interrupted growth model, the implications of which are episodes of 'tumour dormancy'. We propose that the concepts of tumour homeostasis, tumour dormancy and enhancement of metastasis growth related to primary tumour removal, convincingly explaining the clinical behaviour of breast cancer, may be used for uveal melanoma as well. To confirm this proposition, a careful analysis of uveal melanoma metastasis dynamics is strongly warranted.
authors.affiliation: Scientific Directorate, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milano 20133, Italy. demicheliromano@istitutotumori.mi.it.
authors.forename: Romano
authors.initials: R
authors.lastname: Demicheli
authors.forename: Marco
authors.initials: M
authors.lastname: Fornili
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D014604:Uveal Neoplasms / Q000401:mortality* / Q000473:pathology; D000098943:Uveal Melanoma