title: Subsequent malignancies and their effect on survival in patients with retinoblastoma.
abstract: BACKGROUND
  As cure rates for retinoblastoma have improved, it is clear that patients with hereditary retinoblastoma experience increased risk of subsequent malignant neoplasms (SMNs).
  
  
  METHODS
  Using the Surveillance, Epidemiology and End Results (SEER) database, we evaluated risk of SMNs in survivors or retinoblastoma. Standardized mortality ratios (SMRs) were calculated to compare number of deaths observed to the expected number for the cohort. Cumulative incidence of SMNs and standardized incidence ratios (SIRs) of observed to expected SMNs were calculated
  
  
  RESULTS
  A total of 595 patients were included in the analysis. Cumulative incidence of secondary malignancy at 30 years for patients with unilateral and bilateral disease was 1.7% and 28.5%, respectively (P < 0.001). SIRs of subsequent malignancies for patients with unilateral and bilateral disease were 2.1 (95% CI = 0.6-5.4) and 38.3 (95% CI = 24.3-57.5), respectively. Patients with bilateral disease treated with and without radiotherapy both experienced an increased risk of SMNs (SIRs = 45.9, 95% CI = 26.8-73.6 and 27.3, 95% CI = 10.0-59.4, respectively). The most common cause of death for the patients with bilateral disease was subsequent malignancy (52% of deaths). Beginning in the 1990s, there was a significant decrease in the use of radiotherapy as 30.5% of patients received radiotherapy in the 1980s compared to 2.6% after 1999 (P < 0.001).
  
  
  CONCLUSIONS
  Survivors of bilateral retinoblastoma experience an increased risk of SMNs which adversely affects survival. The use of radiotherapy in the management of retinoblastoma has declined; however, patients with bilateral disease remain at an increased risk of subsequent cancers.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Shinohara
authors.forename: Todd
authors.initials: T
authors.lastname: DeWees
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perkins
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects / Q000639:trends; D019572:Retinal Neoplasms / Q000150:complications* / Q000401:mortality / Q000532:radiotherapy; D012175:Retinoblastoma / Q000150:complications* / Q000401:mortality / Q000532:radiotherapy; D018426:SEER Program; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: SEER; retinoblastoma; secondary malignancy