title: Risk of third malignancies and death after a second malignancy in retinoblastoma survivors.
abstract: Retinoblastoma patients have a strongly increased risk of second malignancies, and survivors with a third or subsequent malignancy are increasingly observed. However, it has not been examined whether survivors who developed a second malignancy have a greater risk of a subsequent malignancy. On the basis of the Dutch retinoblastoma registry, the risk of a third malignancy was compared with cancer risk in the Dutch population. Cox model analysis with a time-dependent covariate was used to compare the subsequent malignancy risk and survival among patients with and without a second malignancy. Risk of a third malignancy was increased 8-fold compared with the general population. The hazard ratio (HR) of a third malignancy after a second malignancy was more than 7-fold increased compared to the risk of a second malignancy after retinoblastoma. Radiotherapy increased the risk 3-fold. A third malignancy was associated with worse survival compared with survival of patients only diagnosed with a second malignancy (HR=5.0). Survivors of retinoblastoma who already developed a second primary malignancy have an even higher risk of subsequent primary malignancies than retinoblastoma survivors without a second malignancy. Treating physicians and patients should be aware of this higher risk.
authors.affiliation: Department of Ophthalmology, VU University Medical Center, de Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. t.marees@vumc.nl
authors.forename: T
authors.initials: T
authors.lastname: Marees
authors.forename: F E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: M
authors.initials: M
authors.lastname: Schaapveld
authors.forename: S M
authors.initials: SM
authors.lastname: Imhof
authors.forename: M R
authors.initials: MR
authors.lastname: de Boer
authors.forename: W A
authors.initials: WA
authors.lastname: Kors
authors.forename: P J
authors.initials: PJ
authors.lastname: Ringens
authors.forename: A C
authors.initials: AC
authors.lastname: Moll
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000401:mortality; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000401:mortality*; D009426:Netherlands / Q000453:epidemiology; D019572:Retinal Neoplasms / Q000401:mortality*; D012175:Retinoblastoma / Q000401:mortality*; D012878:Skin Neoplasms / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000401:mortality; D017741:Survivors / Q000706:statistics & numerical data*