[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.226.208.185. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
July 2018

Treatment of Nonmetastatic Unilateral Retinoblastoma in Children

Author Affiliations
  • 1Pediatric Oncology Service, Hospital San Juan de Dios, Santiago, Chile
  • 2Hematology-Oncology Service, Hospital J. P. Garrahan, Buenos Aires, Argentina
  • 3Oncology Service, Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina
  • 4Hematology-Oncology Service, Hospital Sant Joan de Déu, Barcelona, Spain
  • 5Hematology-Oncology Service, Hospital Calvo Mackenna, Santiago, Chile
  • 6Hematology-Oncology Service, Hospital Pereyra Rossell, Montevideo, Uruguay
  • 7Ophthalmology Service, Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina
  • 8Ophthalmology Service, Hospital Calvo Mackenna, Santiago, Chile
  • 9Pathology Service, Hospital Calvo Mackenna, Santiago, Chile
  • 10Ophthalmology Service, Hospital Sant Joan de Déu, Barcelona, Spain
  • 11Pathology Service, Hospital Sant Joan de Déu, Barcelona, Spain
  • 12Ophthalmology Service, Hospital San Juan de Dios, Santiago, Chile
  • 13Ophthalmology Service, Hospital J. P. Garrahan, Buenos Aires, Argentina
  • 14Ophthalmic Pathology Department, Fundación Oftalmologica Malbran, Buenos Aires, Argentina
  • 15Pathology Service, Hospital J. P. Garrahan, Buenos Aires, Argentina
  • 16Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Washington, DC
  • 17Division of Hematology/Oncology, Children’s Hospital of Michigan, Detroit
JAMA Ophthalmol. 2018;136(7):747-752. doi:10.1001/jamaophthalmol.2018.1501
Key Points

Question  Which children receive adjuvant therapy for unilateral retinoblastoma?

Findings  In this single-arm multicenter study in Latin America with 175 children, overall survival was 100% in those with low risk of relapse and no receipt of adjuvant therapy and 95% in those with high risk of relapse and receipt of an intensive chemotherapy regimen. Preoperative chemotherapy was administered in children with buphthalmia.

Meaning  These data suggest that adjuvant chemotherapy may not be needed in children having unilateral retinoblastoma with low risk of relapse; a schema of intense adjuvant chemotherapy may be effective in preventing extraocular relapse.

Abstract

Importance  Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management.

Objective  To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria.

Design, Setting, and Participants  This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017.

Interventions  Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles.

Main Outcomes and Measures  Probability of event-free survival (extraocular relapse and death from any cause were considered events).

Results  Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death).

Conclusions and Relevance  Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.

×