Minimal Disseminated Disease in Nonmetastatic Retinoblastoma With High-Risk Pathologic Features and Association With Disease-Free Survival

LAURENT, VIVIANA E.; TORBIDONI, ANA VANESA; SAMPOR, CLAUDIA; OTTAVIANI, DANIELA; VAZQUEZ, VALERIA; GABRI, MARIANO R.; GARCIA DE DAVILA, MARIA TERESA; RAMIREZ-ORTIZ, MARCO A.; ALONSO, CRISTINA NOEMI; ROSSI, JORGE; ALONSO, DANIEL F.; CHANTADA, GUILLERMO L.

JAMA Ophthalmology

AMER MEDICAL ASSOC

Año: 2016 vol. 134

2168-6165

Importance: Fatal metastatic relapse may occur in children with retinoblastomaand high-risk pathologic features (HRPFs). Minimal dissemination (MD) may be anadditional tool for risk estimation. The use of cone-rod homeobox (CRX)transcription factor messenger RNA for MD evaluation in metastatic retinoblastomawas previously reported, but no data in nonmetastatic cases with HRPFs areavailable.Objectives: To evaluate whether MD is detectable in patients with nonmetastaticretinoblastoma and to assess its prognostic effect on disease-free survival(DFS).Design, Setting, and Participants: This single-institution cohort study ofpatients with nonmetastatic retinoblastoma and HRPFs used prospectively definedinclusion criteria and a sampling strategy to procure bone marrow (BM) andcerebrospinal fluid (CSF) samples from May 1, 2007, through October 31, 2013.Median follow-up was 38 months (range, 8-89 months). Survival analysis was closedin December 2015, and no further updates were made after that point.Interventions: The study evaluated CRX messenger RNA by quantitative polymerasechain reaction in BM and CSF at diagnosis and follow-up. In 14 patients, GD2synthase was used instead of CRX for CSF evaluation. Patients were treated under uniform guidelines.Main Outcomes and Measures: Metastatic relapse.Results: The study included 96 children (median age at study inclusion, 26months; range, 1-168 months; 46 male [47.9%]; 50 female [52.1%]) withnonmetastatic retinoblastoma and HRPFs (isolated massive choroidal invasion in14, postlaminar optic nerve invasion in 51 [26 with concomitant massive choroidaland 13 with scleral invasion], 12 with scleral invasion without postlaminar opticnerve invasion, and 7 with tumor at the resection margin of the optic nerve) wereevaluated at the time of primary or secondary enucleation. Minimal dissemination was detected in 9 patients (7 BM samples and 2 CSF samples) and was associatedwith extension beyond the resection margin of the optic nerve and scleralinvolvement, but only the former was independently associated (adjusted oddsratio, 57.0; 95% CI, 4.8-678.2; P = .001). In addition, MD occurred in 8 of the43 International Intraocular Retinoblastoma Classification group E eyes withglaucoma (18.6%) and in 8 of 80 (10%) and 1 of 16 children (6.3%) who underwentprimary or secondary enucleation, respectively. Children with MD had a 3-year DFSof 0.78 compared with 0.98 in those without MD (95% CI for the difference in DFS,0.17-0.23; P = .004).Conclusions and Relevance: These findings identified a high-risk population ofchildren 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 higherrisk of MD at diagnosis, should not be considered definitive at this time.