title: The time course of irradiation changes in proton beam-treated uveal melanomas.
abstract: BACKGROUND
  Although histopathologic changes in uveal melanomas treated by irradiation have been well characterized, the timing of these effects after irradiation has not been previously evaluated.
  
  
  METHODS
  The series consisted of a total of 92 eyes with uveal melanoma, enucleated at various intervals after proton irradiation (range, 1 month to 8 years) due to complications (n = 66) or tumor growth (n = 22), or at autopsy (n = 4). Study slides were read, using a standard protocol, by two pathologists masked to the timing of the enucleation after irradiation and the reason for the surgery.
  
  
  RESULTS
  The prevalence of inflammation decreased whereas fibrosis increased with time from 15% of cases enucleated within 12 months (early cases) to 61% of those enucleated more than 30 months (late cases) after irradiation (P for trend = 0.0005). Tumor necrosis and blood vessel damage occurred early, and the prevalence of these changes was constant over time. Excluding tumors with evidence of growth after irradiation, mitotic figures became progressively less common as the interval between irradiation and enucleation increased (P for trend = 0.015); no mitotic figures were present in 40 high-power fields more than 30 months after irradiation.
  
  
  CONCLUSIONS
  Histopathologic changes in irradiated melanomas vary according to the time elapsed since irradiation. Inflammation decreases with time whereas fibrosis becomes more prevalent with time after irradiation. Among controlled tumors, mitotic figures appear only in recently irradiated tumors.
authors.affiliation: Retina Service, Massachusetts Eye and Ear Infirmary, Boston 02114.
authors.forename: E S
authors.initials: ES
authors.lastname: Gragoudas
authors.forename: K M
authors.initials: KM
authors.lastname: Egan
authors.forename: M A
authors.initials: MA
authors.lastname: Saornil
authors.forename: S M
authors.initials: SM
authors.lastname: Walsh
authors.forename: D M
authors.initials: DM
authors.lastname: Albert
authors.forename: J M
authors.initials: JM
authors.lastname: Seddon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017357:Cyclotrons; D015353:Eye Enucleation; D005355:Fibrosis; D006801:Humans; D008545:Melanoma / Q000473:pathology* / Q000532:radiotherapy; D008875:Middle Aged; D015995:Prevalence; D011522:Protons; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology; D011878:Radiotherapy / Q000009:adverse effects; D013997:Time Factors; D014604:Uveal Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D014605:Uveitis / Q000209:etiology / Q000473:pathology
chemical_list: D011522:Protons