title: Second cranio-facial malignancies in hereditary retinoblastoma survivors previously treated with radiation therapy: clinic and radiologic characteristics and survival outcomes.
abstract: BACKGROUND
  Hereditary retinoblastoma survivors have an increased risk for cranio-facial second primary tumours (SPT), especially after treatment with external beam radiotherapy (EBRT). This multicentre study evaluates the clinical and imaging characteristics and outcomes of cranio-facial SPTs in irradiated retinoblastoma survivors.
  
  
  METHODS
  Clinical and radiological data of 42 hereditary retinoblastoma patients with 44 second and third malignancies were reviewed. Radiological data included anatomic location and computed tomography (CT) and magnetic resonance (MR) characteristics. Cox regression and likelihood ratio chi-square test were used to evaluate differences in patients' survival rates.
  
  
  RESULTS
  Cranio-facial SPTs were diagnosed at a median age of 13 years. Histological types included osteosarcomas (43%), rhabdomyosarcomas (20%) (57% embryonal, 43% alveolar) and a variety of other types of SPT (37%). Predilection sites were: temporal fossa (39%), ethmoid sinus (23%), orbit (18%), maxillary sinus (16%) and intracranial dura mater (4%). Most of the osteosarcomas (78%) and rhabdomyosarcomas (80%) occurred in patients treated with EBRT in the first year-of-life. Treatment of SPTs with a microscopically complete surgical resection led to a significantly better 5-year overall survival (OS) (P=0.017) and event-free survival (EFS) (P=0.012) compared to patients treated without surgery or incomplete resection (OS: 83% versus 52%; EFS: 80% versus 47%).
  
  
  CONCLUSIONS
  Osteosarcomas and rhabdomyosarcomas are the most common cranio-facial SPTs in irradiated hereditary retinoblastoma survivors, which develop in specific locations and occur predominantly in patients irradiated in their first year-of-life. Microscopically complete surgical resection of SPTs is a major prognostic factor, suggesting the potential benefit of early detection by imaging.
authors: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands. f.rodjan@vumc.nl
authors: Firazia
authors: F
authors: Rodjan
authors: Pim de
authors: Pd
authors: Graaf
authors: Hervé J
authors: HJ
authors: Brisse
authors: Jonathan I L M
authors: JI
authors: Verbeke
authors: Esther
authors: E
authors: Sanchez
authors: Paolo
authors: P
authors: Galluzzi
authors: Sophia
authors: S
authors: Göricke
authors: Philippe
authors: P
authors: Maeder
authors: Isabelle
authors: I
authors: Aerts
authors: Remi
authors: R
authors: Dendale
authors: Laurence
authors: L
authors: Desjardins
authors: Sonia
authors: S
authors: de Franscesco
authors: Norbert
authors: N
authors: Bornfeld
authors: Wolfgang
authors: W
authors: Sauerwein
authors: Maja Beck
authors: MB
authors: Popovic
authors: Dirk L
authors: DL
authors: Knol
authors: Annette C
authors: AC
authors: Moll
authors: Jonas A
authors: JA
authors: Castelijns
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D018204:Neoplasms, Connective and Soft Tissue / Q000175:diagnosis* / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000209:etiology; D012516:Osteosarcoma / Q000175:diagnosis / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods; D012175:Retinoblastoma / Q000150:complications / Q000532:radiotherapy*; D012208:Rhabdomyosarcoma / Q000175:diagnosis / Q000209:etiology; D016019:Survival Analysis; D017741:Survivors / Q000706:statistics & numerical data*; D014057:Tomography, X-Ray Computed; D055815:Young Adult