title: Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates.
abstract: OBJECTIVE
  To evaluate whether the removal of the eye after radiotherapy alters the rates of metastatic death in patients with melanoma of the choroid.
  
  
  METHODS
  Using an extension of the Cox model, we based our analysis on a cohort of 1541 consecutive patients with unilateral choroidal or ciliary body melanoma treated with protons (70 cobalt-gray equivalent in 5 to 7 fractions) at the Harvard University (Boston, Mass) cyclotron between July 1, 1975, through December 31, 1993, and who were observed prospectively up to September 30, 1995. Patient survival and the status of the treated eye were updated annually.
  
  
  RESULTS
  By September 1995 (median follow-up among survivors, 8 years), 137 patients underwent enucleation after radiotherapy for complications (n=103) or tumor regrowth (n=34). The overall 10-year rate of eye retention was 89% (95% confidence interval, 87%-91%). Of the 1541 patients, 300 died of tumor metastasis, 38 following enucleation of the affected eye (mean interval from enucleation to death, 25 months). The multivariate rate ratio for metastatic death associated with enucleation (modeled as a time-dependent covariate) was 0.9 (95% confidence interval, 0.6-1.4) for enucleation due to complications and 3.8 (95% confidence interval, 2.3-6.3) for enucleation associated with tumor regrowth.
  
  
  CONCLUSIONS
  In the absence of tumor viability, enucleation after primary irradiation for choroidal melanoma has no deleterious effect on patients' survival. Enucleation concurrent with tumor regrowth is associated with high death rates; growth of the tumor in the eye may presage systemic recurrence and death from metastasis.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard University School of Medicine, Boston 02115, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Egan
authors.forename: L M
authors.initials: LM
authors.lastname: Ryan
authors.forename: E S
authors.initials: ES
authors.lastname: Gragoudas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002830:Choroid Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D003037:Cobalt Radioisotopes / Q000627:therapeutic use*; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D015353:Eye Enucleation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D003037:Cobalt Radioisotopes