Treatment of Nonmetastatic Unilateral Retinoblastoma in Children

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/m 2 /d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m 2 /d, days 1 and 2] and etoposide [100 mg/m 2 /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.

Delayed Enucleation With Neoadjuvant Chemotherapy in Advanced Intraocular Unilateral Retinoblastoma: AHOPCA II, a Prospective, Multi-Institutional Protocol in Central America

“…Twenty-three (51%) had delayed enucleation, and their OS was 0.60 ± 0.13. Although we could not perform accurate comparisons with the prior study because of the lack of complete documentation of buphthalmos, these results are comparable to the Pérez et al 31 Grupo de America Latina de Oncología Pediátrica cohort with buphthalmos treated with neoadjuvant chemotherapy, where one of seven patients with buphthalmos experienced a relapse.…”

The COVID‐19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP‐E, SIOP‐PODC, IPSO, PROS, CCI, and St Jude Global

“…Intraocular retinoblastoma requires access to an experienced ophthalmologist for an immediate examination underanesthesia (EUA) to determine the intraocular extent of disease (cT1‐CT3) and laterality, as this will determine treatment with either local therapy or local and systemic chemotherapy. Routine neuroimaging (MRI) for unilateral intraocular retinoblastoma could be deferred unless there is involvement of the optic nerve or a suspicion of extraocular involvement 39 . Given the likely resource constraints for interventional radiology and prolonged anesthesia, services should consider deferring intraarterial chemotherapy programs.…”

Retinoblastoma: Etiology, Modeling, and Treatment

“…Overall survival was 100% in the low-risk group without receiving systemic chemotherapy and 95% in the high-risk group. The authors suggested that adjuvant chemotherapy may not be necessary for low-risk patients but benefits patients with high-risk retinoblastoma in preventing extraocular relapse [ 10 ].…”

“…Tumors become advanced if treatment is delayed, hindering vision and globe salvages with a risk of metastasis [ 8 , 9 , 10 ]. Chemotherapy is the standard of care for patients with a high risk of metastasis but has inevitable toxicity [ 10 , 11 , 12 , 13 , 14 , 15 ]. Such treatment is also commonly used for globe sparing with different routes of drug delivery depending on the clinical features and anticipated outcomes [ 16 ].…”