title: Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma.
abstract: BACKGROUND
  Survivors of hereditary retinoblastoma have an increased risk for second malignancies, especially soft tissue sarcomas. However, the risks of individual histologic subtypes of soft tissue sarcomas have not been evaluated.
  
  
  METHODS
  We estimated the risk for six subtypes of soft tissue sarcomas (fibrosarcoma, liposarcoma, histiocytoma, leiomyosarcoma, rhabdomyosarcoma, and others) in a cohort of 963 one-year survivors of hereditary retinoblastoma among patients diagnosed at two US institutions from 1914 through 1984. We calculated standardized incidence ratios (SIRs) for specific subtypes of soft tissue sarcomas by comparison with population data from the Connecticut Tumor Registry or from National Cancer Institute Surveillance, Epidemiology, and End Results database. We also calculated the cumulative risk for all soft tissue sarcomas combined.
  
  
  RESULTS
  We observed 69 soft tissue sarcomas in 68 patients with hereditary retinoblastoma. Risks were elevated for soft tissue sarcomas overall (SIR = 184, 95% confidence interval [CI] = 143 to 233) and for individual subtypes. Leiomyosarcoma was the most frequent subtype (SIR = 390, 95% CI = 247 to 585), with 78% of leiomyosarcomas diagnosed 30 or more years after the retinoblastoma diagnosis (SIR = 435, 95% CI = 258 to 687). Among patients treated with radiotherapy for retinoblastoma, we found statistically significantly increased risks of soft tissue sarcomas in the field of radiation. Irradiated patients also had increased risks of soft tissue sarcomas, especially leiomyosarcomas, outside the field of radiation, and risks of soft tissue sarcomas were increased in nonirradiated patients as well, indicating a genetic predisposition to soft tissue sarcomas independent of radiation. The cumulative risk for any soft tissue sarcoma 50 years after radiotherapy for retinoblastoma was 13.1% (95% CI = 9.7% to 17.0%).
  
  
  CONCLUSIONS
  Long-term follow-up of a cohort of survivors of hereditary retinoblastoma revealed a statistically significant excess of leiomyosarcoma and other soft tissue sarcomas that persists decades after the retinoblastoma diagnosis. Retinoblastoma survivors should undergo regular medical surveillance for sarcomas in their adult years.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, EPS 7044, 6120 Executive Blvd., Rockville, MD 20852, USA. kleinerr@mail.nih.gov
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Kleinerman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Seddon
authors.forename: Robert E
authors.initials: RE
authors.lastname: Tarone
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007890:Leiomyosarcoma / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D016017:Odds Ratio; D011159:Population Surveillance; D011878:Radiotherapy / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012042:Registries; D019572:Retinal Neoplasms / Q000235:genetics; D012175:Retinoblastoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D018570:Risk Assessment; D018426:SEER Program; D012509:Sarcoma / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D017741:Survivors / Q000706:statistics & numerical data*; D014481:United States / Q000453:epidemiology