Recent progress in retinoblastoma: Pathogenesis, presentation, diagnosis and management.

Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for survival and preservation of visual acuity hinges upon the disease severity at the time of initial diagnosis. Notably, retinoblastoma has played a crucial role in unraveling the genetic foundations of oncogenesis. The process of tumorigenesis commonly begins with the occurrence of biallelic mutation in the RB1 tumor suppressor gene, which is then followed by a cascade of genetic and epigenetic alterations that correspond to the clinical stage and pathological features of the tumor. The RB1 gene, recognized as a tumor suppressor, encodes the retinoblastoma protein, which plays a vital role in governing cellular replication through interactions with E2F transcription factors and chromatin remodeling proteins. The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

Captains on call: A qualitative investigation of an intervention to support children with retinoblastoma undergoing regular eye examinations.

BACKGROUND: Retinoblastoma is a rare childhood ophthalmic cancer that requires frequent eye examinations under anaesthesia and painful or distressing procedures. This can cause significant anxiety for children and their families. OBJECTIVE: We evaluated a Starlight Children's Foundation programme, 'Captains on Call', at the Queensland Children's Hospital, which aims to provide positive distraction and reduce stress, anxiety and pain during the perioperative journey for children in the retinoblastoma treatment pathway. This study examined the impact of the programme on the perioperative experience of the children and their families, using a qualitative design. METHODS: This study was conducted in a paediatric operating suite at a tertiary-level children's hospital in Australia. We interviewed a parent from 20 families (from a cohort of 40 families, including 44 children), whose children received treatment or screening for retinoblastoma, focusing on the programme's impact on the child and family at various stages during the perioperative journey. We undertook a thematic analysis of transcribed interviews. RESULTS: We identified two themes, each with two sub-themes: (1) the programme positively contributed to the overall treatment journey, by addressing different needs at different times, and helping to reframe a traumatic medical experience, and (2), the programme supported the whole family unit by empowering children through play, and adopting a family systems approach which recognised the impact of cancer treatment on the whole family. CONCLUSION: This study highlights the value of the Captains on Call programme in supporting children with retinoblastoma and their families during perioperative visits. The Captains, particularly as non-medicalised professionals in a healthcare setting, built trust and rapport with the children through play over repeated episodes of care. The interprofessional collaborative approach with a reflective cycle of practice extended it beyond a programme providing simple distraction. Other retinoblastoma services may benefit from implementing a similar approach.

Circulating Tumor DNA Posttreatment Measurements and Clinical Correlates in Retinoblastoma.

Importance: Plasma measurements of RB1 circulating tumor DNA (ctDNA) after completion of treatment may be associated with the development of metastases in patients with retinoblastoma. Objective: To determine if the absence of previously detectable plasma ctDNA is associated with metastasis-free survival in patients with a minimum of 1 year follow-up after treatment of retinoblastoma. Design, Setting, and Participants: This cohort study was conducted from June 2019 to September 2023. Patients with retinoblastoma who had measurable ctDNA levels at diagnosis and had repeated ctDNA measurements after ocular treatment (enucleation or intra-arterial chemotherapy) with a minimum of 1 year of follow-up (mean [SD], 28.2 [10.3] months) were included in the study. Patients were recruited from a single-center, tertiary cancer hospital. Exposure: Memorial Sloan Kettering's New York State-approved gene test, which interrogates 129 known cancer genes (called ACCESS), was performed on plasma samples before and after ocular treatments. All exons of the RB1 gene are included in the test and listed as ctDNA in this article. Main Outcomes and Measures: Plasma ctDNA level before treatment, after completion of ocular treatment, and development or absence of metastases. Results: A total of 24 patients (mean [SD] age, 20.7 [17.1] months; 15 female [62.5%]) were included in the study. None of the 23 patients who had a measurable ctDNA level and then no detectable ctDNA level after completion of ocular treatment developed metastases with a minimum of 1 year of follow-up. One patient had persistent measurable ctDNA after initial treatment and developed metastases. Conclusion and Relevance: Patients with retinoblastoma who had a measurable ctDNA level at diagnosis did not develop metastases if the plasma ctDNA level became unrecordable after ocular treatment; 1 patient who had persistent measurable ctDNA after treatment did develop metastasis.

Familial retinoblastoma: variations in clinical presentation and management based on paternal versus maternal inheritance.

BACKGROUND: Several studies have demonstrated the effect of parent-of-origin on retinoblastoma penetrance. The purpose of the current study was to assess differences in clinical presentation of paternally versus maternally inherited retinoblastoma. METHODS: The clinical records of all children with familial retinoblastoma treated on a tertiary Ocular Oncology Service between December 1975 and May 2020 were reviewed retrospectively. RESULTS: A total of 179 patients with familial retinoblastoma were included. Paternal inheritance (PI) was identified in 109 (61%) patients and maternal inheritance (MI) in 70 patients (39%). A comparison (PI vs MI) revealed PI patients were older at presentation (57.2 vs 24.4 months [P = 0.002]) with no difference in patient sex (53% females vs 57% males [P = 0.606]) or number of family members affected (3.2 vs 3.0 family members [P = 0.255]). PI patients had more advanced classification according to the International Classification of Retinoblastoma (ICRB) (group E: 31% vs 8% [P = 0.012)] and greater largest tumor in basal diameter (9.0 vs 6.2 mm [P = 0.040]) and thickness (5.6 vs 4.0 mm [P = 0.038]); they were also less likely to be located in the macula (40% vs 60% [P = 0.004]). There was no difference in tumor laterality (69% vs 64% bilaterality [P = 0.530]). PI patients required enucleation more frequently (34% vs 14% [P = 0.007]). There was no difference in need for plaque radiotherapy (P = 0.86) or chemotherapy (P = 0.85). One PI patient developed metastatic retinoblastoma, and there were no retinoblastoma-related deaths. CONCLUSIONS: Patients with paternally inherited retinoblastoma presented at an older age, with larger, more peripheral tumors and more advanced ICRB group, and were more likely to require enucleation compared to those with maternally inherited retinoblastoma.

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.

Association of Neighborhood Opportunity With Severity of Retinoblastoma at Presentation.

PURPOSE: To examine the relationship between the Child Opportunity Index (COI) and severity of retinoblastoma at presentation. DESIGN: Cross-sectional study. METHODS: Children (age <18 years) treated for retinoblastoma at a tertiary care center between January 2000 and May 2023 were included. Residential census tract was used to determine the overall and domain-specific COI score for each child. Collected variables included age, sex, race/ethnicity, insurance type, and the International Classification of Retinoblastoma (ICRB) Group at initial examination. The primary outcome was Group D or E retinoblastoma at presentation. Mixed effects regression models were used to estimate the association of COI scores with disease severity at presentation. RESULTS: This study included 125 children (51.2% male). Median age at diagnosis was 13 months (IQR, 5-24 months). One hundred nine (87.2%) children presented with Group D or E retinoblastoma and 33 (26.4%) resided in low or very low opportunity neighborhoods. Children residing in neighborhoods with low overall COI scores (OR, 1.62; 95% CI, 1.01-2.58; P = .044) and low education COI scores (OR, 1.77; 95% CI, 1.13-2.79; P = .013) were at increased odds of presenting with ICRB Group D or E retinoblastoma after adjusting for individual-level socioeconomic factors. CONCLUSION: Children residing in low opportunity neighborhoods-particularly low education opportunity-more often presented with advanced stage retinoblastoma than children residing in neighborhoods with higher opportunity scores. Efforts to improve preventative vision care and access to eye specialty care for children residing in low-resource areas are needed to reduce existing disparities in retinoblastoma.

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.

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.

The Potential of Aqueous Humor Sampling in Diagnosis, Prognosis, and Treatment of Retinoblastoma.

Retinoblastoma (RB) is a rare malignant tumor that arises in the developing retina in one or both eyes of children. Pathogenic variants of the RB1 tumor suppressor gene drive the majority of germline and sporadic RB tumors. Considering the risk of tumor spread, the biopsy of RB tumor tissue is contraindicated. Advancement of chemotherapy has led to preservation of more eye globes. However, this has reduced access to tumor material from enucleation specimens. Recently, liquid biopsy of aqueous humor (AH) has advanced the RB tumor- or eye-specific genetic analysis. In particular, nucleic acid analysis of AH demonstrates the genomic copy number profiles and RB1 pathogenic variants akin to that of enucleated RB eye tissue. This advance reduces the previous limitation that genetic assessment of the primary tumor could be done only after enucleation of the eye. Additionally, nucleic acid evaluation of AH allows the exploration of the genomic landscape of RB tumors at diagnosis and during and after treatment. This review explores how AH sampling and AH nucleic acid analysis in RB patients assist in diagnosis, prognosis, and comprehending the pathophysiology of RB, which will ultimately benefit individualized treatment decisions to carefully manage this ocular cancer in children.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

Risk factors for cataract in retinoblastoma management.

AIMS: To investigate the risk factors for cataract following eye-preserving therapies for retinoblastoma. METHODS: This retrospective, single-centre cohort study included patients diagnosed with retinoblastoma receiving eye-preserving therapies between January 2017 and June 2021. Cataract by the end of the follow-up was the main outcome. RESULTS: Cataract was found in 31 of 184 (16.8%) included eyes during a mean follow-up of 27.6 months. The cataract and control groups were similar regarding patients' laterality, sex and disease stage. Eyes in the cataract group were more likely to present with endophytic retinoblastoma (p=0.02) and greater intraocular pressure (p=0.001). Competing risk regression analysis (univariate Fine-Gray model) showed that the growth pattern (p=0.01), intraocular pressure (p=0.01), number of intra-arterial chemotherapy (IAC) cycles (p=0.001), melphalan dose per IAC cycle (p=0.001) and number of intravitreous chemotherapy (IvitC) cycles (p=0.001) were associated with cataract occurrence. Multivariate analysis included higher intraocular pressure (p=0.003), a higher melphalan dose per IAC cycle (p=0.001) and an increasing number of IvitC cycles (p=0.04) as independent risk factors for cataract. CONCLUSIONS: Repeated IAC and/or IvitC with melphalan were the most common eye-preserving therapies that induced cataract formation. The toxic effect of melphalan was an essential factor in cataract development, as indicated by the association of cataract occurrence with the melphalan dose.

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.

Conservative treatment using laser diode and systemic chemotherapy for early-stage bilateral retinoblastoma: A 14-year prospective cohort study.

BACKGROUND: Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long-term follow-up is scarce, especially in low-resource countries. AIMS: This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low-resource settings. METHODS AND RESULTS: A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three-agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4-20) months, 34 eyes were in group B (68%). The median follow-up time was 60 (60-84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan-Meier analysis found the overall globe-salvage rate at 5 years of 91.9% (95% CI: 80.1%-97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%-90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p = .007, AOR = 8.098, 95% CI: 1.79-36.53) which also shows less enucleation than a type 3 scar (p = .002, AOR = 0.06, 95% CI: 0.01-0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded. CONCLUSION: Conservative treatment of early-stage RB is safe and effective. Long-term, thorough follow-ups of patients post-treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.

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.

Does vitreous haemorrhage and calcification lead to increased risk of enucleation in advanced retinoblastoma?

PURPOSE: To explore whether varying degrees of vitreous haemorrhage (VH) and calcification act as risk factors for enucleation in patients with advanced retinoblastoma (RB). METHODS: Advanced RB was defined by the international classification of RB (Philadelphia version). Basic information for retinoblastoma patients diagnosed as groups D and E in our hospital between January 2017 and June 2022 was reviewed by logistics regression models. Additionally, a correlation analysis was performed, excluding variables with a VIF (variance inflation factor) >10 from the multivariate analysis. RESULTS: A total of 223 eyes diagnosed with RB were included in assessing VH and calcification; of these, 101 (45.3%) eyes experienced VH, and 182 (76.2%) eyes were found to have calcification within the tumour through computed tomography (CT) or B-scan ultrasonography. Ninety-two eyes (41.3%) were enucleated, of which 67 (72.8%) had VH and 68 (73.9%) calcification, both of which were significantly relevant to enucleation (p < 0.001*). Other clinical risk factors, such as corneal edema, anterior chamber haemorrhage, high intraocular pressure during treatment and iris neovascularization, correlated significantly with enucleation (p < 0.001*). Multivariate analysis included IIRC (intraocular international retinoblastoma classification), VH, calcification and high intraocular pressure during treatment as independent risk factors for enucleation. CONCLUSIONS: Despite identifying different potential risk factors for RB, there remains significant controversy concerning which patients require enucleation, and the degree of VH varies. Such eyes need to be evaluated carefully, and management with appropriate adjuvant therapy may improve the outcome of these patients.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. METHODS: Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. RESULTS: Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. CONCLUSION: In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

A multi-institutional feasibility study of intra-arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1).

BACKGROUND: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies. OBJECTIVE: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma. METHODS: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions. Eligible patients older than six months of age were enrolled. The feasibility of delivering three injections of melphalan into the ophthalmic artery every 28 days was assessed. RESULTS: Nine institutions participated in this trial. Fourteen patients were enrolled, two of whom were unevaluable for feasibility. Four patients experienced a feasibility failure. In two patients, the ophthalmic artery could not be accessed for the second IA injection, in one the artery could not be accessed for the first injection, and one patient experienced grade 4 hypotension during the procedure. CONCLUSION: Delivery of prescribed therapy within the context of this study did not meet the feasibility goals of the study with only a 67% feasibility success rate. These results should caution centers that plan to initiate this treatment and suggest investment in training to achieve technical expertise or referral to centers with expertise.

PATIENT-RELATED FACTORS AND CLINICAL MANAGEMENT OUTCOMES OF RETINOBLASTOMA IN CALABAR, NIGERIA.

Background: Retinoblastoma is curable in industrialized countries. However, it is associated with mortality in resource-poor nations due to disparities and poor access to eye care. Aim was to determine the relationships between patient-related factors and clinical outcomes of Retinoblastoma management in a tertiary hospital in Nigeria. Materials and methods: This was a retrospective study of all children who were diagnosed and treated for Retinoblastoma from January 2017 through December 2022. Information obtained from their records included biosocioeconomic data, symptoms, lag time from initial symptoms, staging, treatment and outcome (dead or alive). Results: Fifty-three patients, aged 6 to 88 months on first hospital presentation were recruited. There were 29(54.7%) females and 20(37.7%) patients died. Parental low socioeconomic class, rural residence and poor nutrition occurred more in those that survived, though not significantly (p>0.05). Median(interquartile) age at diagnosis [24(18-36) months, p=0.005] and lag time [13(6-20) months, p=0.274] were low in the survived group. Bilateral Retinoblastoma (20.8%,p=0.002), brain metastasis (22.6%,p<0.001), IRSS IV (18.9%,p=0.01) and relapse (34%,p<0.001) occurred more among the patients that died. The overall survival (OS) was 22(11.77-32.23) months with 1-year OS of 63%. Treatment with only chemotherapy [HR 4.76(95%CI:1.726-13.128)], incomplete chemotherapy [HR 5.61(95%CI:1.271-24.741)], relapse [HR 5.98(95%CI:1.376-25.983)] and eye surgery after 3 chemotherapy cycles [HR 8.22(95%CI:1.087-62.239)] were predictors of mortality. Conclusion: Early presentation of retinoblastoma especially of advanced and bilateral disease may lead to improved survival if chemotherapy and eye surgery are appropriately performed. Routine screening and immediate referral of retinoblastoma particularly in rural areas are recommended.