Incidence of Retinoblastoma Has Increased : Results from 40 European Countries

Funding Information: Obtained funding: N/A; Study was performed as part of the regular employment duties of all authors at their institutions. No additional funding was provided.Non peer reviewe

Global retinoblastoma presentation and analysis by national income level

IMPORTANCE : Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child’s life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. OBJECTIVES : To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTS : A total of 278 retinoblastoma treatment centerswere recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. MAIN OUTCOMES AND MEASURES : Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTS : The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle–income countries and HICs, 17.92 [95%CI, 12.94-24.80], and for lower-middle–income countries vs upper-middle–income countries and HICs, 5.74 [95%CI, 4.30-7.68]). CONCLUSIONS AND RELEVANCE : This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.The Queen Elizabeth Diamond Jubilee Trusthttp://oncology.jamanetwork.com/public/About.aspxam2021Paediatrics and Child Healt

Retinoblastoma survival and enucleation outcomes in 41 countries from the African continent.

Background: Retinoblastoma is the most common intraocular malignancy in childhood. Despite one-third of cases occurring in Africa, little is known of the outcomes on the continent. This study aims to explore survival and globe salvage outcomes and identify their risk factors across a large cohort of patients from the African continent. Methods: A 3-year prospective, observational study was conducted. Kaplan-Meier survival analysis was used to investigate the risk of globe loss and death from retinoblastoma in Africa. Cox regression was used to identify risk factors associated with these outcomes. Results: A total of 958 patients from 41 African countries and 66 participating centres were enrolled in the study. The survival rate was 78.2% at 1 year and 66.2% at 3 years after diagnosis. Cox regression showed a higher risk of death with the most advanced clinical stage (cT4, HR=6.29 vs cT2, p<0.001). The risk of losing at least one eye after diagnosis was 50% within 4 months and 72.6% within 3 years. Higher risk of enucleation was associated with a higher clinical stage compared with cT1 (cT3, HR=4.11, p=0.001; cT4, HR=3.77, p=0.005). Conclusion: Nearly one in every four children diagnosed with retinoblastoma in African participating centres succumb to retinoblastoma within 1 year. There is also high morbidity associated with the diagnosis as a large majority of patients require eye removal surgery. The outcome of disease in children with retinoblastoma in Africa is poor compared with other continents and requires prompt intervention by increasing efforts to improve survival and eye salvage outcomes

Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries.

OBJECTIVE: To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. METHODS: A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. RESULTS: For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). CONCLUSIONS: No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries.

BACKGROUND: Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS: We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS: The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0-36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8-100·0) for children from high-income countries, 91·2% (89·5-93·0) for children from upper-middle-income countries, 80·3% (78·3-82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76-50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44-18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23-1·56). For children aged 3-7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION: This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. FUNDING: Queen Elizabeth Diamond Jubilee Trust

Retinoblastoma Outcomes in the Americas: A Prospective Analysis of 491 Children With Retinoblastoma From 23 American Countries

PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income [LIC], lower-middle income [LMIC], upper-middle income [UMIC], and high income [HIC]) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval [CI] 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients >4 years of age (vs ≤4 years, HR = 0.45 [95% CI 0.27-0.78], P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 × 109 [95% CI 1.25 × 109-1.72 × 1010], P < .001) and females (vs males, HR = 1.98 [95% CI 1.27-3.10], P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 [95% CI 2.36-10.5], P < .001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs