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.

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.

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.

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.

Enhancing information on stage at diagnosis for childhood cancer in Africa.

BACKGROUND/PURPOSE: Stage at diagnosis is an important metric in treatment and prognosis of cancer, and also in planning and evaluation of cancer control. In sub-Saharan Africa (SSA), for the latter, the only data source is the population-based cancer registry (PBCR). For childhood cancers, the 'Toronto Staging Guidelines' have been developed to facilitate abstraction of stage by cancer registry personnel. Although the feasibility of staging using this system has been shown, there is limited information on the accuracy of staging. METHODS: A panel of case records of six common childhood cancers was established. A total of 51 cancer registrars from 20 SSA countries staged these records, using Tier 1 of the Toronto guidelines. The stage that they assigned was compared with that decided by two expert clinicians. RESULTS: The registrars assigned the correct stage for 53%-83% of cases (71% overall), with the lowest values for acute lymphocytic leukaemia (ALL), retinoblastoma and non-Hodgkin lymphoma (NHL), and the highest for osteosarcoma (81%) and Wilms tumour (83%). For ALL and NHL, many unstageable cases were mis-staged, probably due to confusion over the rules for dealing with missing data; for the cases with adequate information, accuracy was 73%-75%. Some confusion was observed over the precise definition of three stage levels of retinoblastomas. CONCLUSIONS: A single training in staging resulted in an accuracy, for solid tumours, that was not much inferior to what has been observed in high-income settings. Nevertheless, some lessons were learned on how to improve both the guidelines and the training course.

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.

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.

Subsequent malignant neoplasms in the pediatric age in retinoblastoma survivors in Argentina.

BACKGROUND: Retinoblastoma survivors in low- and middle-income countries are exposed to high-intensity treatments that potentially place them at higher risk of early subsequent malignant neoplasms (SMNs). METHODS: We followed 714 (403 [56.4%] nonhereditary and 311 [43.5%] hereditary) retinoblastoma survivors diagnosed from August 1987 to December 2016, up to the age of 16 years. We quantified risk of SMNs with cumulative incidence (CI) and standardized incidence ratios (SIR) analysis. Multivariate regression Cox model was used to determine the association of treatments and risk of SMNs. RESULTS: Median follow-up was of 9 years (range: 0.18-16.9) and 24 survivors (3.36%) developed 25 SMNs (n = 22 hereditary, n = 2 nonhereditary). SMNs included sarcomas (osteosarcomas, Ewing sarcomas, rhabdomyosarcomas; n = 12), leukemias (n = 5), and central nervous system tumors (CNS; n = 3). All cases of acute myeloid leukemia (AML) and most of Ewing sarcomas occurred within 5 years of retinoblastoma diagnosis. The type of SMN was the main indicator of mortality (five of five patients with leukemias, six of 12 with sarcomas, and zero of three with CNS tumors died). Compared to the general population, radiation increased the risk of Ewing sarcoma in hereditary survivors by 700-fold (95% CI = 252-2422.6) and chemotherapy increased the risk of AML by 140-fold (95% CI = 45.3-436). The CI of SMNs for hereditary survivors was 13.7% (95% CI = 8.4-22.1) at 15 years. CONCLUSION: Retinoblastoma survivors from Argentina are at higher risk of developing SMNs early in life compared to the general Argentinean population, especially those treated with radiation plus chemotherapy. AML and Ewing sarcoma presented within 5 years of retinoblastoma diagnosis are associated with chemotherapy and radiation exposure.

Retinoblastoma associated with orbital pseudocellulitis and high-risk retinoblastoma: a study of 32 eyes.

PURPOSE: To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. METHODS: Retrospective study of 32 patients who underwent primary enucleation for RB presenting with orbital pseudocellulitis. RESULTS: All RB patients presented with orbital pseudocellulitis. The mean age at presentation of RB was 30 months (median, 24 months; range, 3-70 months). There were 14 (44%) males and 18 (56%) females. All patients were referred with a diagnosis of RB with orbital pseudocellulitis. Tumor was bilateral in 12 (38%) patients but orbital pseudocellulitis was unilateral in all cases. The pseudocellulitis features included proptosis (n = 9; 28%), eyelid edema (n = 22; 69%), conjunctival congestion (n = 23; 72%), and conjunctival chemosis (n = 15; 47%). Based on clinical features and orbital imaging, all patients were diagnosed to have group E intraocular RB. All patients received intravenous steroids prior to enucleation. On histopathology, tumor necrosis was present in all cases with a mean % necrosis of 60% (median, 60%; range, 10% to 90%). Most tumors (72%) were poorly differentiated. High-risk histopathology features were noted in 23 (72%) cases and adjuvant chemotherapy was advised for all these patients. The most common high-risk histopathology features included post-laminar optic nerve infiltration (34%) and scleral infiltration (22%). Over a mean follow-up period of 34 months (median, 9 months; range, < 1-188 months), there was no event of metastasis or death in any patient. CONCLUSION: RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.

How Telemedicine and Centralized Care Changed the Natural History of Retinoblastoma in a Developing Country: Analysis of 478 Patients.

PURPOSE: To evaluate the efficacy of integrating a telemedicine-based twinning partnership and centralized care for retinoblastoma on survival and eye salvage. DESIGN: Four hundred seventy-eight retinoblastoma patients treated at a tertiary referral cancer center (King Hussein Cancer Centre [KHCC]) from 2003 through 2019. PARTICIPANTS: Four hundred seventy-eight retinoblastoma patients treated at KHCC after implementing a telemedicine-based program with St. Jude Children's Research Hospital. METHODS: We reviewed the outcomes of retinoblastoma patients who were treated at KHCC after implementing a telemedicine-based eye salvage program with St. Jude Children's Research Hospital, and we compared that with outcomes for retinoblastoma patients who were treated before implementing a telemedicine-based retinoblastoma service at KHCC. MAIN OUTCOME MEASURES: We analyzed patient demographics, clinical characteristics, treatments received, consultation type and duration, and long-term patient outcomes before and after implementing the twinning program. RESULTS: Over 17 years, 813 eyes from 478 children with retinoblastoma were treated at KHCC. Three hundred thirty-five patients (70%) had bilateral disease. Six patients (4%) with unilateral disease and 66 patients (20%) with bilateral disease had a family history of retinoblastoma. After the twinning program was established in 2003, the mortality rate decreased from 38% to 5% (P < 0.0001), and the overall eye salvage rate increased from 4% to 61% (98% for group A, 93% for group B, 81% for group C, and 48% for group D; P < 0.0001). Initially, all cases were discussed via telemedicine, but as knowledge transfer increased, the proportion of cases that required discussion decreased to less than 3% 10 years later. Similarly, treatment changes based on consultations decreased from 70% to 7% after 10 years. Both survival and eye-salvage rates were comparable at the early and later stages of implementing the twinning program. At a median follow-up of 120 months, 5% of patients had died of metastases or secondary neoplasms, 81% were alive, and 14% were lost to follow-up. CONCLUSIONS: Centralization of care at a single center in developing countries can achieve patient outcomes comparable with those of developed countries via twinning and telemedicine. This benefit can extend to a large region because two thirds of patients treated at KHCC were non-Jordanians.

General cancer screening practices among adult survivors of retinoblastoma: Results from the Retinoblastoma Survivor Study.

We assessed breast, cervical, and colorectal cancer screening practices in adult retinoblastoma (Rb) survivors and non-Rb controls. We found that most Rb survivors adhered to general population cancer screening recommendations. Rates did not differ among Rb survivors and non-Rb controls, or among survivors by laterality, even though bilateral survivors reported higher levels of concern about future health and cancer risk. Older age, being overweight/obese, and lack of recent contact with medical personnel were independently associated with decreased utilization of Pap smear among female Rb survivors. Future studies are warranted to determine whether these associations might provide an opportunity for intervention.

Epidemiology and survival of childhood cancer in Turkey.

INTRODUCTION: The aim of this study is to evaluate demographics, clinical data, and survival rates of children with cancer over 22 years, and to compare the outcomes, before and after a national health reform was performed. MATERIAL AND METHODS: Files of patients, aged 0-19 years, diagnosed with cancer at the Istanbul University Oncology Institute during 1990-2012 were evaluated retrospectively. RESULTS: The mean age at diagnosis of 2413 patients was 7.5 ± 5.1 years (range 3 days to 19 years). Male/female ratio was 1.26. After 2002, the number of patients diagnosed at a localized/low-risk stage compared to advanced stage significantly increased (60.7% vs 65.1%, P = .03). Comparing the period before 2002 to after 2002, a lower percentage of patients were diagnosed with advanced stage non-Hodgkin lymphoma (62.1% vs 45.1%, P = .03), retinoblastoma (9.5% vs 1.4%, P = .005), soft tissue sarcomas (52.1% vs 38.3%, P = .01), neuroblastoma (82.4% vs 56.2%, P = .005), and carcinomas (72.9% vs 65.4%, P = .04) after 2002. The 5-year survival rate of all patients during the entire period was 74.4%. The survival rate significantly increased for non-Hodgkin lymphoma (63.7% vs 91.8%, P < .0001), neuroblastoma (46.8% vs 70.5%, P = .025), and renal tumors (70% vs 92.3%, P = .013) after 2002. CONCLUSIONS: The increase in patients diagnosed at a localized/low-risk stage and the increase in survival of some types of cancer over years is promising. The national health care reform, enabling patients to easily access free health services, increased awareness, improvement in oncological treatment, and supportive care may have contributed to the progress achieved, and may be a model for other developing countries.

Hope level and associated factors among parents of retinoblastoma patients during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The 2019 coronavirus disease (COVID-19) is a global public health emergency. So far, only a limited number of studies have investigated the impact of the COVID-19 pneumonia pandemic on the mental health of parents having children with cancer. This study investigated the hope, and relevant influencing factors (depression, anxiety, demographic data) among parents whose children had retinoblastoma (RB) during the COVID-19 pandemic. METHODS: A cross-sectional survey and a convenient sampling survey were conducted on 317 parents of RB children admitted to the Ninth People's Hospital affiliated with Shanghai Jiao Tong University, School of Medicine, and Qilu Children's Hospital of Shandong University. The survey tools included Demographic Questionnaire, Herth Hope Index (HHI), The Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaires (PHQ)-2. RESULTS: The hope level score of the parents of RB patients was (35.36 ± 4.42), which was at the medium level. The highest dimension of hope score was inner positive readiness and expectancy (12.07 ± 1.57), and the lowest dimension was interconnectedness with self and others (11.50 ± 1.64). The incidence rate of depression and anxiety was 29.97% (95/317) and 41.32% (131/317), respectively. Monoculus or binoculus disease, sleep status, health status, and depression /anxiety had statistically significant effects on the parental hope level (p < 0.05). Multiple linear regression analysis revealed that time since diagnosis, education level, treatment type and depression were independent influencing factors (p < 0.05), accounting for 22.60% of the variation in hope level. CONCLUSION: During the COVID-19 pandemic, medical staff should formulate targeted intervention measures according to different characteristics of ocular disease, time since diagnosis, treatment type, parental educational level and emotional state in order to improve the level of parental hope.

Knowledge and awareness of the general population and healthcare providers about retinoblastoma: It is time to know the glow.

Retinoblastoma is the most frequent primary intraocular tumour in childhood. Early detection of retinoblastoma is the key to successful management with a higher chance of survival. This study aims to assess the knowledge of the general population and healthcare providers about retinoblastoma in term of presentation, risk factors, timing for diagnosis, and complications. A cross-sectional study using an online survey was conducted in three Arab countries (Jordan, Saudi Arabia, and Iraq) between 28 August and 16 September 2020. The questionnaire tool was constructed based on an extensive literature review to explore the study's aim and objectives. Logistic regression was used to identify predictors of better knowledge about retinoblastoma. A total of 3676 participants were involved in the study (Jordan = 2654, Saudi Arabia = 604, and Iraq = 418). The average retinoblastoma knowledge score for the whole study population was 6.25 (SD = 4.12) out of 21, representing 29.8% (out of the maximum possible total score). Participants aged above 50 years old, married individuals, those with a secondary education level, those who work as professionals in industry, those who have more than four children, and those who reported that they were not in direct contact with a large number of children were less likely to be knowledgeable about retinoblastoma presentation, risk factors, the timing for diagnosis, and complications (P < .05). Early detection is the cornerstone for decreasing morbidity and mortality among children with retinoblastoma. However, the awareness and knowledge about retinoblastoma are very limited in our study population. Efforts should be directed at increasing awareness of both the general population and healthcare providers regarding retinoblastoma. Policymakers are responsible for improving knowledge and awareness about retinoblastoma to facilitate early detection of the disease by conducting awareness campaigns in addition to improve screening skills of healthcare providers and providing them with proper screening and diagnostic tools.

HPV infections in retinoblastoma: a systematic review.

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma. METHODS: For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening. RESULTS: Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks. CONCLUSION: The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.

Clinical outcomes and prognosis of Thai retinoblastoma patients.

BACKGROUND: Retinoblastoma (RB) outcomes in Thailand are unfavorable compared to those of developed countries. This study aims to determine whether the clinical outcomes of patients with RB significantly improved after the implementation of new therapeutic approaches and which clinical factors affect survival and globe-saving outcomes. METHODS: The medical records of patients newly diagnosed with RB and treated at Siriraj Hospital between January 2005 and December 2018 were reviewed retrospectively. Clinical data, treatments, and outcomes were collected and analyzed. RESULTS: In 194 eyes (144 patients), leukocoria was the most common presenting feature (76.8%); 129 (66.5%) eyes were staged in group E of the International Classification of Intraocular Retinoblastoma. Of the 149 enucleated eyes, 35 had high-risk histopathological features, mostly choroidal invasion; 45 eyes (23.2%) could be salvaged. The 5-year overall survival rate was 90.3%, an improvement compared to the previous study. The 5-year enucleation-free survival rates of Groups A and B, C, D and E were 100%, 83.1%, 36.7% and 16.6% respectively. Factors associated with a lower survival rate were interval from symptom onset to diagnosis >3 months (hazard ratio (HR): 5.8: 95% confidence interval (CI): 1.637, 20.579) and buphthalmos (HR: 12.57: 95% CI: 3.936, 40.153). Factors associated with high-risk features were secondary glaucoma (HR: 11.016: 95% CI: 1.24, 98.10) and pseudohypopyon (HR: 14.110: 95% CI: 2.16, 92.05). CONCLUSIONS: Survival rates and globe-saving rates appear to have improved; however, advanced-stage presentation remains the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.

Variability in retinoblastoma genome stability is driven by age and not heritability.

Retinoblastoma (RB) is a childhood intraocular cancer initiated by biallelic inactivation of the RB tumor suppressor gene (RB1-/- ). RB can be hereditary (germline RB1 pathogenic allele is present) or non-hereditary. Somatic copy number alterations (SCNAs) contribute to subsequent tumorigenesis. Previous studies of only enucleated RB eyes have reported associations between heritability status and the prevalence of SCNAs. Herein, we use an aqueous humor (AH) liquid biopsy to investigate RB genomic profiles in the context of germline RB1 status, age, and International Intraocular Retinoblastoma Classification (IIRC) clinical grouping for both enucleated and salvaged eyes. Between 2014 and 2019, AH was sampled from a total of 54 eyes of 50 patients. Germline RB1 status was determined from clinical blood testing, and cell-free DNA from AH was analyzed for SCNAs. Of the 50 patients, 23 (46.0%; 27 eyes) had hereditary RB, and 27 (54.0%, 27 eyes) had non-hereditary RB. Median age at diagnosis was comparable between hereditary (13 ± 10 months) and non-hereditary (13 ± 8 months) eyes (P = 0.818). There was no significant difference in the prevalence or number of SCNAs based on (1) hereditary status (P > 0.56) or (2) IIRC grouping (P > 0.47). There was, however, a significant correlation between patient age at diagnosis, and (1) number of total SCNAs (r[52] = 0.672, P < 0.00001) and (2) number of highly-recurrent RB SCNAs (r[52] = 0.616, P < 0.00001). This evidence does not support the theory that specific molecular or genomic subtypes exist between hereditary and non-hereditary RB; rather, the prevalence of genomic alterations in RB eyes is strongly related to patient age at diagnosis.

Risk factors for recurrent retinoblastoma after intravenous chemotherapy.

PURPOSE: To analyze the risk factors and estimate the risk period for tumor recurrence in intraocular retinoblastoma (RB). METHODS: Retrospective study of 60 RB patients. RESULTS: The mean age at presentation with RB was 16 months (median 11 months; range 1-84 months). Tumor was unilateral in 13 (22%) and bilateral in 47 (78%) patients. Of 83 eyes with intraocular RB, group B (n = 27; 33%) tumors were more common based on International Classification of Intraocular Retinoblastoma. All cases received intravenous chemotherapy as a primary treatment. Over a mean follow-up period of 57 months (median 38 months; range 12-185 months) post-primary treatment, 44 (73%) patients developed tumor recurrence. The mean interval between the completion of primary treatment and first tumor recurrence was 5 months (median 3 months; range 1-24 months). The total duration of treatment for complete tumor control including treatment of tumor recurrences was 20 months (median 19 months; 2-58 months). By multivariate analysis, the factors predictive of tumor recurrence were multiple tumors (p = 0.008) and retinal detachment (p = 0.003) at presentation. Kaplan-Meier estimate of tumor recurrence at 6 months, 1 year, 3 years, and 5 years was 20%, 31%, 68%, and 73%, respectively. There was no tumor recurrence beyond 5 years since primary treatment. CONCLUSION: Multiple tumors and retinal detachment at presentation are risk factors for tumor recurrence in RB. Close follow-up is mandatory for at least 5 years since the initiation of treatment for RB.

Recommendations for Long-Term Follow-up of Adults with Heritable Retinoblastoma.

PURPOSE: To generate recommendations for long-term follow-up of adult survivors of heritable retinoblastoma. DESIGN: We convened a meeting of providers from retinoblastoma centers around the world to review the state of the science and to evaluate the published evidence. PARTICIPANTS: Retinoblastoma is a rare childhood cancer of the retina. Approximately 40% of retinoblastoma cases are heritable, resulting from a germline mutation in RB1. Dramatic improvements in treatment and supportive care have resulted in a growing adult survivor population. However, survivors of heritable retinoblastoma have a significantly increased risk of subsequent malignant neoplasms, particularly bone and soft tissue sarcomas, uterine leiomyosarcoma, melanomas, and radiotherapy-related central nervous system tumors, which are associated with excess morbidity and mortality. Despite these risks, no surveillance recommendations for this population currently are in place, and surveillance practices vary widely by center. METHODS: Following the Institute of Medicine procedure for clinical practice guideline development, a PubMed, EMBASE, and Web of Science search was performed, resulting in 139 articles; after abstract and full-text review, 37 articles underwent detailed data abstraction to quantify risk and evidence regarding surveillance, if available. During an in-person meeting, evidence was presented and discussed, resulting in consensus recommendations. MAIN OUTCOME MEASURES: Diagnosis and mortality from subsequent neoplasm. RESULTS: Although evidence for risk of subsequent neoplasm, especially sarcoma and melanoma, was significant, evidence supporting routine testing of asymptomatic survivors was not identified. Skin examination for melanoma and prompt evaluation of signs and symptoms of head and neck disease were determined to be prudent. CONCLUSIONS: This review of the literature confirmed some of the common second cancers in retinoblastoma survivors but found little evidence for a benefit from currently available surveillance for these malignancies. Future research should incorporate international partners, patients, and family members.