title: Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma.
abstract: BACKGROUND
  We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series.
  
  
  METHODS
  Fifteen patients with bone marrow (n = 14), bone (n = 10), orbit (n = 9), and/or liver (n = 4) disease were treated. Induction chemotherapy usually consisted of vincristine, cyclophosphamide, cisplatin, and etoposide. The high-dose chemotherapy regimen included carboplatin and thiotepa alone (n = 1) or with etoposide (n = 5) or topotecan (n = 7).
  
  
  RESULTS
  Bone marrow cleared at first post-initiation of chemotherapy examination in all patients and stem cells were harvested after a median of 3.5 cycles of chemotherapy (range 3-6 cycles). Two patients progressed prior to high-dose chemotherapy and died. Thirteen received high-dose chemotherapy at a median of 6 months post-diagnosis of metastases (range 4-8 months). Ten are retinoblastoma-free in first remission at a median follow-up of 103 months (range 34-202 months) while three recurred (two in the CNS, one in the mandible) 14-20 months post-diagnosis of metastases. Retinoblastoma-free and event-free survival at 5 years are 67% (95% confidence interval 38-85%) and 59% (95% confidence interval 31-79%). Six of the 10 survivors received radiation therapy. Three patients developed secondary osteosarcoma 14, 4, and 9 years after diagnosis of metastatic disease.
  
  
  CONCLUSIONS
  Intensive multimodality therapy including high-dose chemotherapy with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma treated. The contribution of external beam radiation therapy is unclear.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. dunkeli@mskcc.org
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Dunkel
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Khakoo
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.forename: Timothy
authors.initials: T
authors.lastname: Gershon
authors.forename: Stephen
authors.initials: S
authors.lastname: Gilheeney
authors.forename: David C
authors.initials: DC
authors.lastname: Lyden
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Wolden
authors.forename: Manuela
authors.initials: M
authors.lastname: Orjuela
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Gardner
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D012008:Recurrence; D019572:Retinal Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy*; D012175:Retinoblastoma / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin