title: Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma.
abstract: OBJECTIVE
  To identify the clinical features of eyes with retinoblastomas that predict the recurrence of retinal tumors, vitreous seeds, and subretinal seeds following treatment with chemoreduction.
  
  
  METHODS
  Prospective nonrandomized single-center clinical trial.
  
  
  METHODS
  Ocular oncology service at Wills Eye Hospital of Thomas Jefferson University (Philadelphia, Pa) in conjunction with the division of oncology at Children's Hospital of Philadelphia.
  
  
  METHODS
  There were 158 eyes with 364 tumors in 103 consecutive patients with retinoblastoma managed with chemoreduction between June 1994 and August 1999.
  
  
  METHODS
  All patients received treatment for retinoblastoma with 6 cycles of chemoreduction using vincristine, etoposide, and carboplatin combined with focal treatment (cryotherapy, thermotherapy, or plaque radiotherapy) for each retinal tumor.
  
  
  METHODS
  The 3 main outcome measures included recurrence of retinal tumors, recurrence of vitreous seeds, and recurrence of subretinal seeds. The clinical features at the initial examination were analyzed for their association with the main outcome measures using a series of Cox proportional hazards regressions.
  
  
  RESULTS
  All retinal tumors, vitreous seeds, and subretinal seeds showed an initial favorable response of regression during this treatment regimen. Using Kaplan-Meier estimates, at least 1 retinal tumor recurrence per eye was found in 37% of eyes at 1 year, 51% at 3 years, and no further increase at 5 years. By multivariate analysis, the only factor predictive of retinal tumor recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 54 eyes that had vitreous seeds at the initial examination, vitreous seed recurrence was found in 26% of eyes at 1 year, 46% at 3 years, and 50% at 5 years. By univariate analysis, the only factor predictive of vitreous seed recurrence was the presence of tumor-associated subretinal seeds at the initial examination. Of the 71 eyes that had subretinal seeds at the initial examination, subretinal seed recurrence was detected in 53% of eyes at 1 year, 62% at 3 years, and no further increase at 5 years. By multivariate analysis, factors predictive of subretinal seed recurrence included a tumor base greater than 15 mm and a patient age of 12 months or younger at diagnosis. There were no patients who developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms.
  
  
  CONCLUSIONS
  Chemoreduction combined with focal therapy is effective for selected eyes with retinoblastomas. Eyes with subretinal seeds at initial examination are at particular risk for recurrence of retinal tumor and vitreous seeds. Younger patients with large tumors are at risk for recurrence of subretinal seeds. Retinal tumor and subretinal seed recurrence seems to manifest within 3 years of follow-up. Close follow-up of all patients treated with chemoreduction is warranted.
authors.affiliation: Ocular Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107, USA.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Shields
authors.forename: Santosh G
authors.initials: SG
authors.lastname: Honavar
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Shields
authors.forename: Hakan
authors.initials: H
authors.lastname: Demirci
authors.forename: Anna T
authors.initials: AT
authors.lastname: Meadows
authors.forename: Thomas John
authors.initials: TJ
authors.lastname: Naduvilath
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005047:Etoposide / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000556:secondary; D006801:Humans; D007223:Infant; D009364:Neoplasm Recurrence, Local; D009366:Neoplasm Seeding; D011446:Prospective Studies; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D012175:Retinoblastoma / Q000188:drug therapy* / Q000556:secondary; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*; D014822:Vitreous Body / Q000473:pathology*
chemical_list: D014750:Vincristine; D005047:Etoposide; D016190:Carboplatin