title: Minimal Disseminated Disease in Nonmetastatic Retinoblastoma With High-Risk Pathologic Features and Association With Disease-Free Survival.
abstract: OBJECTIVE
  Fatal metastatic relapse may occur in children with retinoblastoma and high-risk pathologic features (HRPFs). Minimal dissemination (MD) may be an additional tool for risk estimation. The use of cone-rod homeobox (CRX) transcription factor messenger RNA for MD evaluation in metastatic retinoblastoma was previously reported, but no data in nonmetastatic cases with HRPFs are available.
  
  
  OBJECTIVE
  To evaluate whether MD is detectable in patients with nonmetastatic retinoblastoma and to assess its prognostic effect on disease-free survival (DFS).
  
  
  METHODS
  This single-institution cohort study of patients with nonmetastatic retinoblastoma and HRPFs used prospectively defined inclusion criteria and a sampling strategy to procure bone marrow (BM) and cerebrospinal fluid (CSF) samples from May 1, 2007, through October 31, 2013. Median follow-up was 38 months (range, 8-89 months). Survival analysis was closed in December 2015, and no further updates were made after that point.
  
  
  METHODS
  The study evaluated CRX messenger RNA by quantitative polymerase chain reaction in BM and CSF at diagnosis and follow-up. In 14 patients, GD2 synthase was used instead of CRX for CSF evaluation. Patients were treated under uniform guidelines.
  
  
  METHODS
  Metastatic relapse.
  
  
  RESULTS
  The study included 96 children (median age at study inclusion, 26 months; range, 1-168 months; 46 male [47.9%]; 50 female [52.1%]) with nonmetastatic retinoblastoma and HRPFs (isolated massive choroidal invasion in 14, postlaminar optic nerve invasion in 51 [26 with concomitant massive choroidal and 13 with scleral invasion], 12 with scleral invasion without postlaminar optic nerve invasion, and 7 with tumor at the resection margin of the optic nerve) were evaluated at the time of primary or secondary enucleation. Minimal dissemination was detected in 9 patients (7 BM samples and 2 CSF samples) and was associated with extension beyond the resection margin of the optic nerve and scleral involvement, but only the former was independently associated (adjusted odds ratio, 57.0; 95% CI, 4.8-678.2; P = .001). In addition, MD occurred in 8 of the 43 International Intraocular Retinoblastoma Classification group E eyes with glaucoma (18.6%) and in 8 of 80 (10%) and 1 of 16 children (6.3%) who underwent primary or secondary enucleation, respectively. Children with MD had a 3-year DFS of 0.78 compared with 0.98 in those without MD (95% CI for the difference in DFS, 0.17-0.23; P = .004).
  
  
  CONCLUSIONS
  These findings identified a high-risk population of children with retinoblastoma and HRPFs with MD. Because the number of events was small, these results, which suggest that children with International Intraocular Retinoblastoma Classification group E retinoblastoma and glaucoma have a higher risk of MD at diagnosis, should not be considered definitive at this time.
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Viviana E
authors: VE
authors: Laurent
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Ana Vanesa
authors: AV
authors: Torbidoni
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Claudia
authors: C
authors: Sampor
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Daniela
authors: D
authors: Ottaviani
authors: Pathology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Valeria
authors: V
authors: Vazquez
authors: Molecular Oncology Laboratory, Quilmes National University, Bernal, Buenos Aires, Argentina.
authors: Mariano R
authors: MR
authors: Gabri
authors: Pathology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Maria Teresa
authors: MT
authors: Garcia de Davila
authors: Hospital Infantil de México Federico Gomez, Ciudad de México, Distrito Federal, México.
authors: Marco A
authors: MA
authors: Ramirez-Ortiz
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Cristina Noemi
authors: CN
authors: Alonso
authors: Immunology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Jorge
authors: J
authors: Rossi
authors: Molecular Oncology Laboratory, Quilmes National University, Bernal, Buenos Aires, Argentina.
authors: Daniel F
authors: DF
authors: Alonso
authors: Hematology-Oncology Service, Pediatric Hospital S.A.M.I.C. Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
authors: Guillermo L
authors: GL
authors: Chantada
mesh_terms: D001118:Argentina / Q000453:epidemiology; D001706:Biopsy; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012160:Retina / Q000473:pathology; D019572:Retinal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D012175:Retinoblastoma / Q000175:diagnosis* / Q000401:mortality; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate / Q000639:trends; D013997:Time Factors