Clinical, epidemiological, and care profile of hospitalized patients with retinoblastoma in Brazil.

PURPOSE: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. METHODS: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0-19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). RESULTS: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1-14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. CONCLUSIONS: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services.

Retinoblastoma patients treated in Sri Lanka from 2014 to 2020: epidemiology, clinical status and correlates of lag time in seeking tertiary care services.

BACKGROUND: Retinoblastoma (RB) is a tumour of children < 5 years with a incidence of 1 in 20,000. Around 20 RB cases are diagnosed yearly in Sri Lanka, a lower middle-income country with high literacy levels and healthcare free at point of delivery. Incidence, local and systemic severity and mortality related to RB are reportedly high in low- and middle- income countries in comparison to higher income countries. Aims of this study were to describe demographic, socioeconomic, and clinical characteristics of Sri Lankan RB patients attending the designated RB unit at the Lady Ridgeway Hospital (LRH), Colombo between January 2014 to December 2020, and determine correlates of lag time (LT) for first tertiary care visit after detecting the first symptom/sign. METHODS: Two descriptive cross-sectional studies (DCSS) were conducted, one on 171 RB patients with demographic and clinical data collected between 2017 and 2020. In 2021, the second DCSS took place where socioeconomic and further demographic data were collected using telephone interviews, recruiting a subgroup of 90 (53%), consenting and contactable RB patient/ parent pairs. Bivariate and multivariable analyses were applied to determine correlates of LT of > 4 weeks for first tertiary care visit. Results were expressed as odds ratios and 95% confidence intervals. RESULTS: LRH survey (N = 171): Median age at diagnosis was 15 months (range 1-94 months; IQR: 8-27); 89 (52%) were females. Groups D and E tumours were 25.7% (n = 44) and 62.6% (n = 107) respectively with 121 (71%) enucleations. The number of deaths were 2 (1.2%). Telephone survey (N = 90): Proportion with LT of > 4 weeks for first tertiary care visit was 58% (n = 52). None of the putative risk factors (ethnicity, parental educational level, socioeconomic status, distance from residence to tertiary care unit and receiving financial assistance) were associated with LT in both analyses. CONCLUSION: Despite a high proportion with groups D and E tumours and enucleations, mortality rate was low, most likely due to availability of designated tertiary care. No correlates for LT of > 4 weeks for tertiary care presentation were identified. Early RB detection needs rigorous implementation of screening strategies and increased awareness among primary care health workers and parents.

Updated retinoblastoma incidence and outcome in children in Taiwan from 1980 to 2019: a 40-year nationwide study.

BACKGROUND: Retinoblastoma is a potentially fatal disease, and its incidence and mortality varies among different countries and periods. METHODS: This is a nationwide population-based retrospective study from January 1980 to December 2019 in Taiwan. Patients diagnosed as retinoblastoma were identified from the Taiwan National Cancer Registry. To update the literature on retinoblastoma incidence, mortality and trends in Taiwan, we analysed changes in incidence and survival rates over time according to sex, diagnostic age, laterality and treatment. RESULTS: During 1980-2019, the incidence of retinoblastoma in Taiwan was 1 per 16 489 live births (95% CI: 13 415-19 564). The diagnostic age decreased from 2.21 ± 0.26 during 1980-1984 to 1.24 ± 0.26 during 1985-2019. Compared with that observed during 1980-1989, the incidence rate observed after 1990 increased significantly in children aged <10 years (RR: 1.62-2.40, P = 0.0049 to < 0.0001). From 1980 to 2019, the incidence rate for the 0-4-year age group increased and that for the 5-9-year age group remained constant. The mean diagnostic age for bilateral retinoblastoma (0.36 ± 0.47 years) was significantly less than that for unilateral retinoblastoma (1.37 ± 0.35 years) during 2007-2019 (P < 0.0001). The 10-year survival rate was highest in the enucleation group (89.8%) compared with radiotherapy (52.2%) and others (70.0%; P < 0.0001). CONCLUSIONS: During 1980-2019 in Taiwan, the incidence of retinoblastoma increased significantly, and the diagnostic age decreased, which are similar to the ones from other developed countries. However, the survival rate was still lower than that of most developed countries.

Global retinoblastoma studies: A review.

In the current era of global health awareness for retinoblastoma (RB), the challenge that lies ahead of us is providing optimal care for children affected with RB in underdeveloped nations. The understanding of similarities and disparities between various nations across the world aids in achieving comparable outcomes. With dissolving geographic barriers and evolving collaboration, global collaborative studies on RB are becoming increasingly common. They provide real-world, robust evidence on several aspects of RB. This review discusses insights gained from global RB studies regarding the demographics, certain aspects of etiopathogenesis and epidemiology, international travel burden, disparities in clinical presentations based on national income levels, management protocols, pathology, treatment outcomes, and the effect of COVID-19 on RB care across the world. These insights are likely to impact individual practice as well as inform policy reforms.

The association between race and age of diagnosis of retinoblastoma in United States children.

PURPOSE: To explore the associations between race and retinoblastoma diagnosis in United States children. METHODS: In this analytical nonconcurrent cohort study, we used 1988-2018 data from the Surveillance, Epidemiology, and End-Results (SEER) database. Children ages 0-17 with retinoblastoma were included (n = 758); those with missing data were excluded (n = 11; final cohort: n = 747). The exposure variable was race (White, Black, Asian/Pacific Islanders, American Indian/Alaska Native), and the outcome variable was diagnosis of retinoblastoma before versus after 2 years of age. Covariates included sex, rural-urban continuum, ethnicity, decade of diagnosis, and laterality of disease. Unadjusted and adjusted logistic regression analyses were performed to calculate odds ratios and 95% confidence intervals. RESULTS: No statistically significant association was found between racial/ethnic groups (OR = 0.61-0.99; P = 0.92) and age at diagnosis (OR = 0.86; P = 0.66). Females were more likely to be diagnosed earlier than males (OR = 0.62; 95% CI, 0.44-0.88; P = 0.042). No association was found between urban versus rural subjects (OR = 1.02; 95% CI, 0.60-1.75) or between decades (OR = 0.81; 95% CI, 0.54-1.22 and OR 0.96; 95% CI, 0.62-1.47). CONCLUSIONS: We found no statistically significant difference between racial/ethnic groups for diagnosis of children with retinoblastoma after 2 years of age. Future studies could explore why females are more likely than males to be diagnosed before 2 years of age.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

INTRODUCTION: Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. METHOD: We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. RESULTS: Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. CONCLUSIONS: Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.

PURPOSE: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration. MAIN OUTCOME MEASURES: Enucleation and death. RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Incidence Trends, Clinicopathologic Characteristics, and Overall Survival Prediction in Retinoblastoma Children: SEER Prognostic Nomogram Analysis.

BACKGROUND: Retinoblastoma is the most common intraocular malignant tumor occurring among children, with an incidence rate of 1/15 000. This study built a joinpoint regression model to assess the incidence trend of retinoblastoma from 2004 to 2015 and constructed a nomogram to predict the overall survival (OS) in children. MATERIALS AND METHODS: Patients less than 19 years diagnosed with retinoblastoma from 2004 to 2015 were selected from the SEER database. Joinpoint regression analysis (version 4.9.0.0) was performed to evaluate the trends in retinoblastoma incidence rates from 2004 to 2015. Cox Regression Analysis was applied to investigate prognostic risk factors that influence OS. RESULTS: Joinpoint regression revealed that retinoblastoma incidence exhibited no significant increase or decrease from 2004 to 2015. As per the multiple Cox regression, tumor size, laterality, and residence (rural-urban continuum code) were correlated with OS and were used to construct a nomogram. The nomogram exhibited a good C-index of 0.71 (95% CI, 0.63 to 0.79), and the calibration curve for survival probability demonstrated that the predictions corresponded well with actual observations. CONCLUSIONS AND RELEVANCE: A prognostic nomogram integrating the risk factors for retinoblastoma was constructed to provide comparatively accurate individual survival predictions. If validated, this type of assessment could be used to guide therapy in patients with retinoblastoma.

Neonatal per- and polyfluoroalkyl substance exposure in relation to retinoblastoma.

BACKGROUND: Neonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk. MATERIALS AND METHODS: This study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately. RESULTS AND DISCUSSION: Among all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase). PFNA was not associated with retinoblastoma risk. CONCLUSIONS: Our results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.

Clinical Patterns And Outcomes Of Retinoblastoma In A Tertiary Care Centre Of A Developing Country.

A retrospective study was conducted for which records of patients with Retinoblastoma (RB), treated at Lahore General Hospital between 2017 and 2021, were retrieved on February 1, 2022. Staging of RB, neuroimaging, RetCam images, and treatment were analysed. The study included 47 patients (22 females and 25 males). Mean age of presentation was 26.5±15 months. Records of 84 eyes (37 bilateral and 10 unilateral) were examined. Family history was positive in only (n=3) 6.3% cases. Mean follow-up was 22.94±14.4 months. Leucocoria was the commonest presentation, seen in 72 (85.7%) eyes, proptosis in 8 (9.5%), huge fungating mass in 2 (2.4%), while tumour was diagnosed because of screening in 2 (2.4%) patients. Posttreatment complications included cataract in two patients, Ischaemic chorioretinal toxicity, transient macular oedema, orbital oedema and transient intra cranial oedema in one patient each. Two patients had metastasis and underwent systemic chemotherapy. The study showed that patients with retinoblastoma can achieve better results if diagnosed early and treated with newer treatment options.

The association between maternal nutrient intake during pregnancy and the risk of sporadic unilateral retinoblastoma among offspring.

Previous studies have associated maternal diet during pregnancy with the development of sporadic unilateral retinoblastoma (RB), but few studies have focused on the role of individual nutrients. The aim of this study is to investigate the association between maternal nutrient intake during pregnancy and the development of sporadic unilateral RB in the offspring. A modified food frequency questionnaire, with additional questions on supplement use, was completed via a phone interview. Cases were recruited from hospitals and controls were comprised of friends and relatives of the patient without a history of cancer. Overall, 168 sporadic unilateral RB cases and 145 controls were included in case-control study. We performed logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI), adjusting for child's age, child's sex, parental race/ethnicity, maternal education, total calorie intake during pregnancy, maternal age at birth, maternal smoking during pregnancy, pre-pregnancy body mass index, maternal weight gain during pregnancy, paternal age at birth, and maternal multivitamin use in the year before pregnancy. In the adjusted model, the interquartile (IQR) increase in vitamin A intake, which was measured in retinol activity equivalent (RAE; OR: 0.64, 95 % CI: 0.46-0.90), and vitamin D intake (OR: 0.62, 95 % CI: 0.42-0.91) significantly reduced the risk of sporadic unilateral RB. These findings suggest that a higher intake of vitamins A and D can be a protective factor for sporadic unilateral RB. Further analyses in consideration of multi-exposures such as parental occupational exposures are warranted to discover the complex etiology of sporadic unilateral RB. In addition, the role of nutritional epigenetics for how maternal nutrient intake influences the risk of sporadic unilateral RB in the offspring still needs to be explored.

Incidence and geographic distribution of retinoblastoma in Ethiopia.

INTRODUCTION: Retinoblastoma is the most frequent intraocular malignancy of the eye in children, occurring in early childhood. Based on global estimates, Ethiopia is expected to observe over 200 new retinoblastoma cases per year, however without a cancer registry, this number is difficult to confirm. Therefore, the goal of the study was to determine the incidence and geographic distribution of retinoblastoma in Ethiopia. METHODS: A retrospective medical chart review of clinically diagnosed new retinoblastoma patients between January 1, 2017 - December 31, 2020, in four public Ethiopian tertiary hospitals was performed. The incidence of retinoblastoma was calculated by a birth-cohort analysis. RESULTS: There were 221 retinoblastoma patients observed in the study period. The incidence of retinoblastoma was found to be 1 in 52,156 live births. Incidence varied among different regions of Ethiopia. CONCLUSION: The incidence of retinoblastoma observed in this study is likely an underestimate. It is possible that patients were undercounted because they were seen outside of the 4 main retinoblastoma treatment facilities included in this facility, or they experienced barriers to accessing care. Our study suggests a need for a nationwide retinoblastoma registry and more retinoblastoma treatment centers in the country.

Incidental detection of retinoblastoma from accidental trauma in children.

BACKGROUND: To report a case series of patients who were diagnosed with retinoblastoma (RB), which was preceded by trauma, in a large multicenter cohort and to investigate the incidence, clinical characteristics, and causes of RB misdiagnosis. METHODS: The medical records of consecutive patients with RB between 2006 and 2015 were retrospectively reviewed. Characteristics of trauma patients, including their age at initial trauma, site of trauma, sex, and RB laterality, were analyzed. RESULTS: Among 3780 patients, 30 (0.8%) experienced systemic or ocular trauma prior to the detection of RB. The median age was 20.7 months, and the median follow-up time was 6 years. There were 2 eyes in stage A, 2 in stage B, 3 in stage C, 12 in stage D, and 15 in stage E. The remaining 2 eyes had extraocular RB. A total of 20 patients experienced ocular trauma, 9 patients experienced head trauma, and 1 patient experienced trauma in other body parts. RB was suspected or detected in 22 patients (73.3%) at the time of primary trauma occurrence, and 8 patients (26.7%) were misdiagnosed with RB during their first visit. Among them, all experienced blunt ocular trauma, and enucleation was performed in 7 patients in which 1 patient died. CONCLUSIONS: Less than 1% of the patients experienced systemic or ocular trauma before RB was detected. The majority were unilateral and in advanced stages. Differential diagnoses that are not trauma-related must always be considered, and comprehensive examinations must be conducted before diagnostic and therapeutic intraocular procedures are initiated.

Referral patterns for retinoblastoma patients in Ethiopia.

BACKGROUND: Increased lag time between the onset of symptoms and treatment of retinoblastoma (RB) is one of the factors contributing to delay in diagnosis. The aim of this study was to understand the referral patterns and lag times for RB patients who were treated at Menelik II Hospital in Addis Ababa, Ethiopia. METHOD: A single-center, cross- sectional study was conducted in January 2018. All new patients with a confirmed RB diagnosis who had presented to Menelik II Hospital from May 2015 to May 2017 were eligible. A questionnaire developed by the research team was administered to the patient's caregiver by phone. RESULTS: Thirty-eight patients were included in the study and completed the phone survey. Twenty-nine patients (76.3%) delayed seeing a health care provider for ≥ 3 months from the onset of symptoms, with the most common reason being the belief that it was not a problem (96.5%), followed by 73% saying it was too expensive. The majority of patients (37/38, 97.4%) visited at least 1 additional health care facility prior to reaching a RB treatment facility. The mean overall lag time from noticing the first symptom to treatment was 14.31 (range 0.25-62.25) months. CONCLUSION: Lack of knowledge and cost are major barriers to patients first seeking care for RB symptoms. Cost and travel distance are major barriers to seeing referred providers and receiving definitive treatment. Delays in care may be alleviated by public education, early screening, and public assistance programs.

Presence of cataract in patients treated for retinoblastoma at the national institute of pediatrics in Mexico (2011-2021).

PURPOSE: The goal of this study is to describe the presence of secondary cataract in patients with retinoblastoma treated at the National Institute of Pediatrics of Mexico (INP) over the past 10 years. METHODS: This was a single center observational, retrospective and descriptive study. We included all eyes diagnosed with retinoblastoma and cataract between June 2011 and June 2021. RESULTS: In total, 833 records of patients diagnosed with Retinoblastoma at the National Institute of Pediatrics during the period between June 2011 and June 2021 were reviewed. Out of all of them, only 14 developed cataract (1.6%). The median age at retinoblastoma diagnosis was 10.5 months (Rank: 6-13 months), and the median age at cataract diagnosis was 51.5 months (Rank: 25-73 months). The majority (13, 92.9%) of the patients had bilateral involvement. 42% of the eyes were Stage D according to the international classification of retinoblastoma. Cryotherapy was applied in 57.1%, intravitreal chemotherapy in 85.7%, radiation therapy in 42.6%, and only 7.1% of cases were treated with intra-arterial chemotherapy. CONCLUSIONS: The presence of cataract in patients with retinoblastoma is a rare but important entity impacting the development of vision in children and detection of intraocular tumors. These probably occur late as a result of the multiple treatments to which the children have been subjected, without being able to determine in this study which is the risk factor most associated with the development of this pathology.

Survival disadvantage of male children with retinoblastoma in the United States: Surveillance Epidemiology and End Results (2000-2017) Evidence.

BACKGROUND: Retinoblastoma is a rare malignancy involving the retina, although, more common among children, with genetic inheritance explaining the incidence as well as acquired forms. The incidence varies among race and sex as well as mortality and survival. The current study aimed to assess retinoblastoma cumulative incidence (CMI), mortality, and survival by sex. METHODS: A retrospective cohort design was used to assess the CMI, mortality, and survival in this pediatric malignancy based on the Surveillance Epidemiology and End Results (SEER) data 2000-2017. The binomial regression model was used to examine sex differentials in mortality, as well as other study variables, while Cox proportional hazard model was used for the survival variability by sex. RESULTS: The CMI during this period was higher among males relative to females (males n = 249, 56.7%; females n = 190, 43.3%, χ2  = 2.90, df = 1, p = 0.089). There were sex differences in mortality, with excess mortality observed among males compared to females, risk ratio = 3.40, 95% CI [1.0-15.72]. The survival differences by sex indicated decreased survival among males relative to females, hazard ratio (HR) = 3.39, 95% CI [1.0-15.72]. After controlling for the potential confoundings, namely tumor grade, urbanity, and median income the survival disadvantage of males persisted. Compared to females', males were more than three times as likely to die, adjusted HR = 3.42, 99% CI [0.37-31.60]. CONCLUSION: In a representative sample of pediatric retinoblastoma, there was a sex differential in survival with excess risk of dying identified among males relative to females, which may be explained in part by male X-linkage.

Seasonal Variation in the Diagnosis of Retinoblastoma.

PURPOSE: To determine the seasonal variation in the diagnosis of retinoblastoma in a global sample of children and to investigate predictors of seasonal trends. METHODS: Data were collected through a global, multicenter, 1-year cross-sectional analysis that included all treatment- naïve retinoblastoma patients presenting to participating centers between January 1, 2017, and December 31, 2017. Due to variations in days per month, data were normalized to a 30-day/month calendar. Observed data were compared to a simulation study of expected results using a uniform distribution. RESULTS: Patient-level data were available for 4,351 children from 276 centers in 153 countries, of which 3,966 had a month of presentation recorded. There were relative peaks in disease presentation in January and July, with lower counts in November and December (p = .0015). No covariates were found to be significantly associated with the seasonal trend. Two covariates, patient age at presentation and extraocular tumor spread, showed a moderate association with month of presentation. CONCLUSION: Our findings suggest seasonal trends in the presentation of retinoblastoma across the world. However, these trends do not appear to be related to income level of a country, climate, or other covariates. Any connection between seasonal variation of retinoblastoma presentation and retinoblastoma outcomes remains unclear or not present.