Search

Importance: Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features., Objective: To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features., Design, Setting, and Participants: This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024., Interventions: Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation., Main Outcomes and Measures: The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children., Results: All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, -7.5% to 9.8%]), which met the noninferiority criterion (P = .003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group., Conclusions and Relevance: Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy., Trial Registration: ClinicalTrials.gov Identifier: NCT01906814.

Purpose: To determine the direct medical costs and cost-effectiveness of globe salvage compared with primary enucleation in patients with advanced retinoblastoma., Methods: Patients with International Classification of Retinoblastoma groups C-E retinoblastoma at a single institution from 2001 to 2021 were categorized into two groups: primary enucleation and globe salvage. Hospital visits and treatments were compared to determine differences in care utilization. Costs per encounter were derived from billing data and multiplied by number of encounters to determine total costs in the first year of treatment. Groups were stratified by unilateral or bilateral retinoblastoma, and visual acuity-based utility values were used to compare quality-adjusted life years to determine cost-effectiveness., Results: Of 74 group C-E eyes of 70 patients, 55 eyes underwent primary enucleation and 19 eyes underwent globe salvage, 12 of which ultimately underwent secondary enucleation. Patients who underwent globe salvage had higher usage of systemic chemotherapy (P = 0.001), more examinations under anesthesia (P < 0.001), fewer outpatient visits (P = 0.03), and a higher total cost of care (301,151 vs 104,764 USD [P < 0.001]) in the first year of treatment compared with the primary enucleation group. At an average life expectancy of 76 years, the incremental cost-effectiveness ratio was 118,347 USD per QALY in unilateral retinoblastoma and 32,987 USD per QALY in bilateral retinoblastoma, meeting the <150,000 USD/QALY threshold of cost-effectiveness., Conclusions: Incurring additional costs may save the eye in advanced retinoblastoma, but the possibility of secondary enucleation should be disclosed for informed decision making. Despite this risk, globe salvage was cost-effective in unilateral and bilateral retinoblastoma., (Copyright © 2023 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels., Design: International, multicenter, registry-based retrospective case series., Participants: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents., Methods: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes., Main Outcome Measures: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy)., Results: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001)., Conclusions: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about socioeconomic status (SES) and its effects in childhood cancer survival. This study aims to discuss the association between SES and survival of patients with retinoblastoma (RB) from a tertiary treatment center., Procedure: A retrospective cohort study was conducted, including all patients with RB referred to the Brazilian National Institute of Cancer in Rio de Janeiro (January 2000-December 2016)., Results: Data from 160 patients were analyzed with mean age at diagnosis of 22.85 months (SD ± 14.29). Eighty-three patients (51.9%) had an interval to diagnosis equal to or longer than six months, and 13 children (8.1%) abandoned treatment. Five-year overall survival rate for all patients was 78.8% (95% CI, 72.4%-85.9%). In a multivariate model, patients whose fathers had more than nine years of study had a lower death risk. Patients from families having more than one child under five years had a 213% higher risk of death compared with those living with no other small child. Treatment abandonment also had a profound effect on death risk., Conclusion: Childhood cancer is notably important considering the potential years of life lost. RB has even more important elements, as the possibility of vision loss in cases with delayed diagnosis. Family characteristics seem to be highly related to RB survival, especially in low- and middle-income countries, where inequalities are still a public health issue. Strategies to improve survival should focus not only on large-scale settings such as improving national healthcare systems but also on more personalized actions that might help to mitigate disparities., (© 2020 Wiley Periodicals LLC.)

India has the highest number of retinoblastoma (RB) patients among the developing countries owing to its increasing population. Of the patients with RB, about 40% have the heritable form of the disease, making genetic analysis of the RB1 gene an integral part of disease management. However, given the large size of the RB1 gene with its widely dispersed exons and no reported hotspots, genetic testing can be cumbersome. To overcome this problem, we have developed a rapid screening strategy by prioritizing the order of exons to be analyzed, based on the frequency of nonsense mutations, deletions and duplications reported in the RB1-Leiden Open Variation Database and published literature on Indian patients. Using this strategy for genetic analysis, mutations were identified in 76% of patients in half the actual time and one third of the cost. This reduction in time and cost will allow for better risk prediction for siblings and offspring, thereby facilitating genetic counseling for families, especially in developing countries.

The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC) to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

Purpose: To evaluate the direct costs and analyze the potential cost-driving factors in the first year of retinoblastoma treatment in China., Methods: Sixty-nine pediatric patients who received multidisciplinary treatment for retinoblastoma in three tertiary hospitals from 2006 to 2011 were included in this retrospective study. The direct costs, including costs for chemotherapy, focal therapy, anesthetic procedure, enucleation, fundus examination, hospitalization and outpatient appointment, transportation, and accommodation for family members, were obtained from medical records and interviews., Results: The average direct costs for retinoblastoma treatment was U.S. $9,422 ± 3,709 per patient during the first year. Of this amount, chemotherapy-related expenses were $2,991 ± 3,083 (31.74%), transportation and accommodation expenses were $2,560 ± 1,348 (27.17%), general anesthetic procedure was $1,081 ± 2,711 (11.48%), and enucleation was $900 ± 1,015 (9.56%). The costs for intra-arterial chemotherapy ($1,224 ± 754) and chemotherapy drugs ($517 ± 134) were major components in chemotherapy-related expenses. The retinoblastoma clinical stage and family income positively correlated with the total direct costs (P = .0358 and .0185, respectively)., Conclusion: Comprehensive treatment involving chemotherapy imposes an enormous economical burden on families affected by retinoblastoma in China., (Copyright 2012, SLACK Incorporated.)

The presenting features of retinoblastoma in developing countries and their correlation with disease stage and patient survival are poorly known and they may be useful as background information for planning early diagnosis initiatives. Therefore, we undertook a retrospective review of 508 patients (467 evaluable, 296 unilateral) treated in Argentina from 1988 to 2008. Patients presented at an older age than reported from high-income countries [mean age 24 mo (range, 0 to 165 mo), 31 mo for unilateral (range, 0 to 165 mo), and 13.3 mo (range, 0 to 62 mo) for bilateral disease]. Leukocoria was the most common presenting sign (n=402, 86%). Strabismus was the only complaint in 25 (5.3%) patients. Forty-two patients (9%) presented with an enlarged eyeball and 37 (7.9%) with a red eye. Retinoblastoma was diagnosed in 22 (4.7%) asymptomatic children. These patients and those with strabismus alone were significantly younger and had a significantly better survival. Children presenting with enlarged eyeballs were significantly older and had significantly lower survival. In multivariable analysis older age and presentation with enlarged eyeballs were independently associated to advanced stage and mortality (P<0.001). Retinoblastoma is diagnosed in later stages in our setting and presentation with eye enlargement and increasing age at diagnosis correlate with worse outcome.