title: Pediatric second primary malignancies after retinoblastoma treatment.
abstract: BACKGROUND
  Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation.
  
  
  METHODS
  All national patients treated for retinoblastoma at the German referral center with a current age of 6-27 years were invited to participate in a study to characterize late effects.
  
  
  RESULTS
  Data on pediatric second primary malignancies were recorded from 488 patients. Ten developed a malignancy before the age of 18 years. For children with heterozygous oncogenic RB1 alteration (heritable retinoblastoma), the cumulative incidence to develop a second malignancy at the age of 10 years was 5.2% (95% CI 1.7; 8.7%). This results in an elevated risk for sarcoma (n = 4) (SIR 147.98; 95% CI 39.81; 378.87) and leukemia (n = 4) (SIR 41.38; 95% CI 11.13; 105.95). Neither the functional type of the RB1 alteration nor its origin showed a significant impact. Treatment modality influenced incidence, latency, and type of malignancy. Previous radiotherapy increased the risk for solid tumors and 3 of 91 children developed acute leukemia after chemotherapy. However, 2 of 10 malignancies were diagnosed in patients with heritable retinoblastoma but without previous chemotherapy or external beam radiotherapy.
  
  
  CONCLUSIONS
  Screening for second primary malignancy is an important part of pediatric oncological follow-up in patients with heritable retinoblastoma. For patients with sporadic unilateral retinoblastoma, genetic information influences treatment decisions and allows tailoring of follow-up schedules.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.|Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Temming
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Viehmann
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Arendt
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors.forename: Lewin
authors.initials: L
authors.lastname: Eisele
authors.affiliation: German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Spix
authors.affiliation: Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|Department of Ophthalmology, University Hospital Essen, Essen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Bornfeld
authors.affiliation: Department of Radiotherapy, University Hospital Essen, Essen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sauerwein
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|Institute of Human Genetics, University Hospital Essen, Essen, Germany.
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Lohmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011878:Radiotherapy / Q000009:adverse effects; D019572:Retinal Neoplasms / Q000628:therapy*; D012175:Retinoblastoma / Q000628:therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: RB1; chemotherapy; mosaic; radiotherapy; retinoblastoma gene 1; sarcoma