title: Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center.
abstract: Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye-preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined.
  
  
  
  This population-based study characterizes the impact of all treatment modalities on second cancers incidence and type after retinoblastoma treatment in Germany. Data on second cancer incidence in 648 patients with heritable retinoblastoma treated between 1940 and 2008 at the German national reference center for retinoblastoma were analyzed to identify associations with treatment.
  
  
  
  The cumulative incidence ratio (per 1,000 person years) of second cancers was 8.6 (95% confidence interval 7.0-10.4). Second cancer incidence was influenced by type of retinoblastoma treatment but not by the year of diagnosis or by sex. Radiotherapy and systemic chemotherapy increased the incidence of second cancers (by 3.0- and 1.8-fold, respectively). While radiotherapy was specifically associated with second cancers arising within the periorbital region in the previously irradiated field, chemotherapy was the strongest risk factor for second cancers in other localizations. Soft tissue sarcomas and osteosarcomas were the most prevalent second cancers (standardized incidence ratio 179.35 compared to the German population).
  
  
  
  Second cancers remain a major concern in heritable retinoblastoma survivors. Consistent with previous reports, radiotherapy increased second cancer incidence and influenced type and localization. However, chemotherapy was the strongest risk factor for second malignancies outside the periorbital region. Our results provide screening priorities during life-long oncological follow-up based on the curative therapy the patient has received and emphasize the need for less-detrimental therapies for children with heritable retinoblastoma.
authors: Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.|Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors: Petra
authors: P
authors: Temming
authors: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors: Marina
authors: M
authors: Arendt
authors: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.|Institute of General Medicine, University Hospital Essen, Essen, Germany.
authors: Anja
authors: A
authors: Viehmann
authors: Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors: Lewin
authors: L
authors: Eisele
authors: Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|Department of Ophthalmology, University Hospital Essen, Essen, Germany.
authors: Claudia H D
authors: CH
authors: Le Guin
authors: Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.
authors: Michael M
authors: MM
authors: Schündeln
authors: Department of Ophthalmology, University Hospital Essen, Essen, Germany.
authors: Eva
authors: E
authors: Biewald
authors: Department of Pediatric Oncology, Hematology and BMT, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Kathy
authors: K
authors: Astrahantseff
authors: Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.
authors: Regina
authors: R
authors: Wieland
authors: Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|Department of Ophthalmology, University Hospital Essen, Essen, Germany.
authors: Norbert
authors: N
authors: Bornfeld
authors: Department of Radiotherapy, University Hospital Essen, Essen, Germany.
authors: Wolfgang
authors: W
authors: Sauerwein
authors: Department of Pediatric Oncology, Hematology and BMT, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Angelika
authors: A
authors: Eggert
authors: German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.|Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
authors: Karl-Heinz
authors: KH
authors: Jöckel
authors: Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.|German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.|Institute of Human Genetics, University Hospital Essen, Essen, Germany.
authors: Dietmar R
authors: DR
authors: Lohmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011379:Prognosis; D019572:Retinal Neoplasms / Q000473:pathology / Q000628:therapy*; D012175:Retinoblastoma / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D017741:Survivors; D055815:Young Adult
keywords: RB1; alkylating agents; radiotherapy; retinoblastoma; sarcoma; second primary malignancy