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

Abstract

IMPORTANCE:

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.

OBJECTIVES:

To evaluate whether MD is detectable in patients with nonmetastatic retinoblastoma and to assess its prognostic effect on disease-free survival (DFS).

DESIGN, SETTING, AND PARTICIPANTS:

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.

INTERVENTIONS:

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.

MAIN OUTCOMES AND MEASURES:

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 AND RELEVANCE:

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: Viviana E Laurent, Ana Vanesa Torbidoni, Claudia Sampor, Daniela Ottaviani, Valeria Vazquez, Mariano R Gabri, Maria Teresa Garcia de Davila, Marco A Ramirez-Ortiz, Cristina Noemi Alonso, Jorge Rossi, Daniel F Alonso, Guillermo L Chantada
• Journal: JAMA ophthalmology (JAMA Ophthalmol) Vol. 134 Issue 12 Pg. 1374-1379 (Dec 01 2016) ISSN: 2168-6173 [Electronic] United States
• PMID: 27787537 (Publication Type: Journal Article)

Topics

• Argentina (epidemiology)
• Biopsy
• Child, Preschool
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Infant
• Infant, Newborn
• Male
• Neoplasm Staging
• Prognosis
• Prospective Studies
• Retina (pathology)
• Retinal Neoplasms (diagnosis, mortality)
• Retinoblastoma (diagnosis, mortality)
• Risk Factors
• Survival Analysis
• Survival Rate (trends)
• Time Factors