title: Second primary osteosarcomas in patients with retinoblastoma.
abstract: OBJECTIVE
  Second primary malignancies have become the leading cause of death in retinoblastoma survivors. Although osteosarcoma is the most common second malignancy, little is known about its clinical and therapeutic features.
  
  
  METHODS
  We retrospectively reviewed a database of patients with retinoblastoma and osteosarcoma occurring as a second malignancy between 1964 and 2010 at the National Cancer Center Hospital of Japan.
  
  
  RESULTS
  Among 857 patients with retinoblastoma registered in the database, 10 (1.1%) developed osteosarcoma as a second malignancy. The median age at the onset of retinoblastoma was 3 months, being bilateral in nine patients and unilateral in one. Systemic chemoreduction was performed in three patients and intra-arterial chemotherapy in six; all patients received external beam radiotherapy. The median age at the onset of second primary osteosarcoma was 11.2 years; four were radiation-related and six were located in an extremity. Among five patients treated at our institute, four patients with tumors on an extremity were treated by wide resection with neoadjuvant and adjuvant chemotherapy. Three of these four patients (75%) were good responders to high-dose methotrexate-based multi-agent chemotherapy and survived with no evidence of disease (median follow-up period, 17.3 years). One patient whose temporal bone was affected underwent radiotherapy with chemotherapy but died after local recurrence.
  
  
  CONCLUSIONS
  The clinical outcomes of second primary osteosarcoma in an extremity occurring in retinoblastoma survivors may be more favorable than those of conventional osteosarcoma. Early diagnosis of radiation-related osteosarcoma arising in the craniofacial region should be made at a stage where complete resection is possible.
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Division of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Numoto
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Division of Pathology, National Cancer Center Hospital, Tokyo.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Division of Orthopaedic Surgery, Chiba Cancer Center, Chiba, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Yonemoto
authors.affiliation: Division of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo akawai@ncc.go.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D005121:Extremities / Q000601:surgery; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007261:Infusions, Intra-Arterial; D007564:Japan / Q000453:epidemiology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D020360:Neoadjuvant Therapy / Q000379:methods; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D012516:Osteosarcoma / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant; D019572:Retinal Neoplasms / Q000473:pathology*; D012175:Retinoblastoma / Q000473:pathology*; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors
chemical_list: D008727:Methotrexate
keywords: chemotherapy; osteosarcoma; radiotherapy; retinoblastoma; surgery