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Studies are lacking on long-term effects among retinoblastoma patients in low- and middle-income countries. Therefore, we examined cause-specific mortality in a retrospective cohort of retinoblastoma patients treated at Antonio Candido de Camargo Cancer Center (ACCCC), São Paulo, Brazil from 1986 to 2003 and followed up through December 31, 2018. Vital status and cause of death were ascertained from medical records and multiple national databases. We estimated overall and cause-specific survival using the Kaplan-Meier survival method, and estimated standardized mortality ratios (SMRs) and absolute excess risk (AER) of death. This cohort study included 465 retinoblastoma patients (42% hereditary, 58% nonhereditary), with most (77%) patients diagnosed at advanced stages (IV or V). Over an 11-year average follow-up, 80 deaths occurred: 70% due to retinoblastoma, 22% due to subsequent malignant neoplasms (SMNs) and 5% to non-cancer causes. The overall 5-year survival rate was 88% consistent across hereditary and nonhereditary patients (p = .67). Hereditary retinoblastoma patients faced an 86-fold higher risk of SMN-related death compared to the general population (N = 16, SMR = 86.1, 95% CI 52.7-140.5), corresponding to 42.4 excess deaths per 10,000 person-years. This risk remained consistent for those treated with radiotherapy and chemotherapy (N = 10, SMR = 90.3, 95% CI 48.6-167.8) and chemotherapy alone (N = 6, SMR = 80.0, 95% CI 35.9-177.9). Nonhereditary patients had only two SMN-related deaths (SMR = 7.2, 95% CI 1.8-28.7). There was no excess risk of non-cancer-related deaths in either retinoblastoma form. Findings from this cohort with a high proportion of advanced-stage patients and extensive chemotherapy use may help guide policy and healthcare planning, emphasizing the need to enhance early diagnosis and treatment access in less developed countries., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Retinoblastoma is the most common intraocular malignancy in childhood. Despite one-third of cases occurring in Africa, little is known of the outcomes on the continent. This study aims to explore survival and globe salvage outcomes and identify their risk factors across a large cohort of patients from the African continent., Methods: A 3-year prospective, observational study was conducted. Kaplan-Meier survival analysis was used to investigate the risk of globe loss and death from retinoblastoma in Africa. Cox regression was used to identify risk factors associated with these outcomes., Results: A total of 958 patients from 41 African countries and 66 participating centres were enrolled in the study. The survival rate was 78.2% at 1 year and 66.2% at 3 years after diagnosis. Cox regression showed a higher risk of death with the most advanced clinical stage (cT4, HR=6.29 vs cT2, p<0.001). The risk of losing at least one eye after diagnosis was 50% within 4 months and 72.6% within 3 years. Higher risk of enucleation was associated with a higher clinical stage compared with cT1 (cT3, HR=4.11, p=0.001; cT4, HR=3.77, p=0.005)., Conclusion: Nearly one in every four children diagnosed with retinoblastoma in African participating centres succumb to retinoblastoma within 1 year. There is also high morbidity associated with the diagnosis as a large majority of patients require eye removal surgery. The outcome of disease in children with retinoblastoma in Africa is poor compared with other continents and requires prompt intervention by increasing efforts to improve survival and eye salvage outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Retinoblastoma, the most common intraocular malignancy in children, has high fatality rates if untreated. It is crucial to monitor treatment effectiveness and explore factors influencing favorable outcomes. Our study aims to examine how tumor location impacts the response to standard treatments and the achievement of favorable outcomes among retinoblastoma patients, while controlling for other tumor-related factors., Methods: This retrospective study analyzed medical records of retinoblastoma patients from November 2012 to December 2022 enrolled in the retinoblastoma program at the Children's Cancer Center of Lebanon (established in collaboration with St.y Jude Children's Research Hospital, Memphis, TN). Data were extracted from the electronic chart reviews and operative reports of examinations under anesthesia (EUAs), and included patient's demographics, tumor characteristics (size, location), and treatment parameters (treatment type, resolution, recurrence)., Results: The study included 42 patients with retinoblastoma, with a total of 57 eyes and 115 tumors/lesions. The median age at diagnosis was 12 months (range: 2-36 months). Among the patients, 26 (61.9%) were males and 16 (38.1%) were females. A minority of patients (21.4%) presented with unilateral involvement, whereas the majority (78.6%) had bilateral involvement. The locations of retinoblastoma lesions were distributed as follows: optic nerve (4.4%), macula (19.1%), superior (16.5%), inferior (17.4%), nasal (27.8%), and temporal (14.8%). Resolution rate tended to be highest for tumors close to optic nerve and temporal lesions, but no statistical significance was attained (p = .45). Macular lesions tended to have the fastest resolution, but again not significantly (p = .5). Multiple logistic regression revealed that the odds for resolution of tumor was not significantly associated with tumor size (p = .57) or location (p = .52)., Conclusion: Location of retinoblastoma lesions was not directly associated with recurrence-free resolution in our cohort. Further research in large retinoblastoma databases is needed to explore the association of tumor characteristics with recurrence and the need for secondary therapeutic interventions., (© 2024 Wiley Periodicals LLC.)

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

Background: The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown., Methods: We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions., Results: Twelve of 16 patients (n = 75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5 years., Conclusions: CSI (23.4 Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB., (© 2024 Wiley Periodicals LLC.)

Objective: To assess the impact of evolving criteria for group E retinoblastoma on ocular survival outcomes., Design: A retrospective observational study., Methods: Single-institution consecutive case series of patients with advanced intraocular retinoblastoma (groups D and E) were classified based on International Intraocular Retinoblastoma Classification (IIRC) and International Classification of Retinoblastoma (ICRB) criteria. The main outcomes measured were ocular survival, frequency of histopathologic risk factors (HRF), and the need for adjuvant therapy., Results: A total of 332 eyes of 298 patients were classified into group D (150, 45%) and E eyes (182, 55%) based on IIRC criteria. ICRB classification resulted in upstaging of 57 group D eyes (17%) to group E. Eyes that were upstaged to group E from D in the ICRB classification (E1) differed significantly, with a greater proportion undergoing primary enucleation (17 of 57, 30%) than those that were not (10 of 93, 11%) (p = 0.003). Similar significant differences were observed between group E2 and E3 eyes (p < 0.0001). Ocular survival according to Kaplan-Meier estimates at 12 months of 79%, 59%, 49%, and 1% differed significantly between all groups (ICRB D, E1, E2, and E3, respectively)., Conclusion: Proposed new subgrouping of group E eyes into E1, E2, and E3 based on clinical criteria is based upon natural history of tumor progression and is predictive of ocular survival. Preservation of the existing lower boundaries for group E by ICRB and IIRC offers the possibility of reanalyzing existing published data., Competing Interests: Footnotes and Disclosure Supported Support provided by The Operation Eyesight Universal Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India. The funders had no role in preparing, reviewing, or approving the manuscript. No conflicting relationship exists for any author., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Retinoblastoma, a curable childhood cancer, has been identified as a tracer cancer in the WHO Global Initiative for Childhood Cancer. To document the outcomes of children with retinoblastoma in South Africa, treated as per the first prospective standard national treatment guidelines for childhood cancer in South Africa., Patients and Methods: All children diagnosed with retinoblastoma between 2012 and 2016 in five South African pediatric oncology units were treated with a standard treatment on the basis of the International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries guidelines for high-income settings. Treatment included focal therapy with/without chemotherapy, or enucleation with/without chemotherapy, and orbital radiotherapy, depending on enucleated eye histology. The end point was survival at 24 months, using Kaplan-Meier curves with log-rank (Mantel-Cox) and chi-square (χ2) tests with respective P values reported., Results: A total of 178 children were included in the study; 68% presented with unilateral disease. The median age was 27 months (range 0-118 months) with a male:female ratio of 1:0.75. The overall survival was 79% at 24 months with significant association with stage at diagnosis ( P < .001) and older age over 2 years as opposed to younger than 2 years ( P < .001). Causes of death were disease progression/relapses in 90% (34 of 38) and unknown in 2% (1 of 38), whereas treatment abandonment was 1.7% (3 of 178)., Conclusion: Efficacy with national treatment guidelines was confirmed, and feasibility of implementing standard national childhood cancer treatment guidelines was documented, involving multidisciplinary teams in South Africa. Outcome was significantly associated with stage at diagnosis and age.

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., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making., Methods: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA)., Results: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance., Conclusion: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients' prognoses., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Purpose: To analyze the safety and efficacy of Pars Plana Vitrectomy (PPV) as a treatment for retinoblastoma patients and to evaluate the feasibility., Methods and Patients: We collected 342 eyes who had PPV after systemic chemotherapy in our retrospective study, then analyze the 5-year overall survival and 5-year event-free survival rate, recurrence rate, and metastasis rate. The above data were used to evaluate the feasibility of PPV in the treatment of retinoblastoma., Results: The mean value of follow-up time was 62.9 months from PPV. Of all 342 eyes, 18% eyes underwent enucleation of the eyeball. Excluding Non-PPV related deaths eyes, the 5-year overall survival rates and event-free survival were 95% and 80%; the tumor recurrence rate and metastasis rate were approximately 26% and 1.2%, respectively; the mortality was 3.9%. And the incidence of high-risk pathological factors of enucleated eyes after PPV was 32%., Conclusion: Our results suggest that Pars Plana Vitrectomy as a new approach to preserve the eyeball of RB children is feasible, especially for those patients who cannot be completely controlled by systemic chemotherapy or the tumors with vitreous seeds. Although the outcomes in our study are very optimistic, we also recommend an experienced eye surgeon to perform the operation and strictly control the indications for PPV surgery. And enough systemic chemotherapy is very important before and after surgery., Level of Evidence: Treatment study (Retrospective comparative study), III., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage., Design: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China., Participants: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016., Methods: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses., Main Outcome Measures: Overall survival and final eye preservation., Results: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis., Conclusions: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma., Methods: We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma., Results: Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7-74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%)., Conclusions: Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

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

Background: Although survival rates for retinoblastoma (RB) are over 95% in high-income countries, its high mortality rate in low and middle-income countries remains a great concern. Few studies investigated treatment outcome and factors contributing to RB survival in these latter settings. Aims of this study are to determine treatment outcome of Indonesian children diagnosed with RB and to explore factors predictive of treatment outcome. Methods: This study was a retrospective medical records review combined with an illustrative case report. Children newly diagnosed with RB between January 2011 and December 2016 at a tertiary care referral hospital in Indonesia were included. A home visit was conducted to perform an in-depth interview with a mother of two children affected by RB. Results: Of all 61 children with RB, 39% abandoned treatment, 21% died, 20% had progressive or relapsed disease and 20% event-free survival. Progressive or relapsed disease was more common in older (≥ 2 years at diagnosis, 29%) than young (<2 years at diagnosis, 0%) children (P=0.012). Event-free survival estimate at 5 years was higher in young (42%) than older (6%) children (P=0.045). Odds-ratio for event-free survival was 6.9 (95% CI: 1.747 – 27.328, P=0.006) for young versus older children. Other clinical and socio-demographic characteristics had no significant correlation with treatment outcome or event-free survival. The case report elucidated conditions and obstacles that Indonesian families face when their children are diagnosed with RB. Conclusion: Survival of children with RB in Indonesia is much lower compared to high-income and many other low and middle-income countries. Abandonment of treatment is the most common cause of treatment failure. Older age at diagnosis is associated with more progressive or relapsed disease and worse survival. Interventions to improve general public and health-care providers’ awareness, early detection and treatment adherence are required.

Background: Survival of children with cancer in resource-limited regions is very poor compared to better-resourced regions. Retinoblastoma (RB) is a childhood cancer that is commonly reported in many regions of Africa. RB may be safely and effectively treated by non-specialists, which could facilitate more widespread availability of treatment in under-resourced areas., Methods: A ten-year consecutive series of children with RB treated at Ruharo Eye Centre between December 2009 and November 2019 was prospectively followed up. Chemoreduction followed by surgery is the standard approach to therapy. Costs of therapy and also of travel and food are borne by the program which is unaffordable to most families and necessitates donors. Survival by stage of RB and number of eyes affected was described using Kaplan-Meier plots. Visual acuity was assessed for all children with bilateral disease and the retention of sight during follow-up assessed., Results: Among 665 children with RB, 18.2 % (121 children) presented with metastatic (Stage 4) RB with only two of these children surviving >24 months. Five-year survival was 60.2 % among all children with RB rising to 93.3 % and 87.2 % for children with unilateral and bilateral Stage 1 disease, respectively. Among 184 children with bilateral disease, 130 (70.7 %) retained some level of sight following primary treatment with 91 of those (49.5 % of all bilateral children) retaining vision up to their death or to the end of follow-up., Conclusion: Many children in Uganda present with advanced RB and curative treatment is not possible in this setting. Children diagnosed and treated early have good prospects of survival. Retention of sight among many bilaterally affected children is achievable, facilitating access to normal education. Therefore, the strategic priorities for improving survival are changing community perceptions so that children with eye problems are brought without delay, and widening access to modern treatment by using genereal health workers with standard drugs, backed by financial, social and peer support., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To summarize the clinical features and survival of Chinese patients with trilateral retinoblastoma (TRb), which may help guide early diagnosis and more effective treatments., Design: Retrospective case series., Methods: Clinical records of patients with TRb were reviewed to identify clinical characteristics and outcomes. TRb was diagnosed mainly based on imaging findings of an enlarged solid pineal or sellar mass. Mutation screening was performed using peripheral blood leucocyte DNA from 3 patients., Results: Fourteen patients with TRb were identified from among 3,789 patients with retinoblastoma (0.4%). Thirteen patients had bilateral retinoblastoma and 1 patient had unilateral disease. The follow-up results revealed that 2 patients survived, 3 patients were lost to follow-up, and 9 patients died. The mean overall survival was 9.8 months (95% confidence interval: 2.3-17.2), and the 2-year survival rate was 18.8% (95% confidence interval: 2.9-45.1) based on Kaplan-Meier estimates. Cox regression multivariate analysis showed metastasis at TRb diagnosis was an independent variable of overall survival (hazard ratio: 15.8; 95% confidence interval: 0.24-5.29; P = .032). Three germline mutations in the RB1 gene were detected via next-generation sequencing., Conclusions: TRb is a rare intracranial mid-line neuroblastic disease. Increased awareness of this disease could guide early detection, which has been associated with improved outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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

Aims: To determine the incidence of retinoblastoma (Rb) and subsequent survival in the Finnish population during five decades., Methods: This retrospective observational cohort study comprised all patients with Rb born in Finland during 1964 - 2014 and diagnosed in 2018 (birth cohort analysis) or diagnosed in 1964 - 2014 (standard annual analysis), identified from the Finnish Cancer Registry and the national referral centre. We report age-adjusted incidences and survival according to cause of death., Results: Of children born in 1964 - 2014, 205 developed Rb, whereas 204 Rbs were diagnosed during these years; 196 belonged to both cohorts. Altogether 80 (38%) of the 213 children had heritable Rb and 19 (9%) had familial disease. The sex ratio was 1.34, suggesting male preponderance. Birth cohort analysis showed a median incidence of 6.2 per 100 000 live births (1:16 130) and less variability as compared with standard annual analysis (12.1, 6.5 and 4.4 per million children 0 - 4, 0 - 9 and 0 - 14 years of age, respectively). The incidence of heritable Rb increased with time, reflecting the increase in familial tumours. Five-year mortality rates from Rb were 6.2% and 7.6% for non-heritable and heritable diseases, respectively, and 35-year mortality rates from second malignancies were 0% and 14.3%, respectively. Family history predicted improved survival, whereas the period of diagnosis did not., Conclusion: The incidence of familial Rb has increased, along with improvement in survival in Finland in 1964-2014, whereas the overall incidence of Rb was stable. Long-term risk of dying of second malignancies after heritable Rb was in line with other countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB)., Design: International, multicenter, registry-based retrospective case series., Participants: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents., Methods: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied., Main Outcome Measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait., Results: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease., Conclusions: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Vitreous concentrations of regulatory cytokines were assessed using a cytometric beads assay and association with clinical data was examined. IL-35 and soluble IL-2 receptor α levels were significantly higher in patients with VRL and NIU than those in the control group. The 5-year overall survival (OS) rates for the group with high intravitreal IL-35 was significantly poorer than those for the group with low intravitreal IL-35, who were diagnosed with VRL at the onset (P = 0.024, log-rank test). The 5-year OS rates with intravitreal IL-35 levels above and below the median were 40.0% and 83.3%, respectively. Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset.

Background: The WHO Global Initiative for Childhood Cancer aims to increase survival to at least 60% for all children with cancer globally, with initial focus on six common curable cancer types. Frequent causes of treatment failure in low income countries (LICs) are treatment abandonment and death during treatment. Here, we report on the outcome at the end of treatment of patients with newly diagnosed common and curable cancer types, admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi., Procedure: Outcome at end of treatment was documented and analyzed retrospectively for all children with a working diagnosis of a common and curable cancer type (ALL, Hodgkin disease, Wilms tumor, retinoblastoma, and Burkitt lymphoma) admitted over a 2-year period. Patients with a misdiagnosis were excluded. Outcomes were categorized as alive without evidence of disease, treatment abandonment, death during treatment, or persistent disease., Results: We included 264 patients. Seven patients with a misdiagnosis were excluded. At the end of treatment, 53% (139 of 264) of patients were alive without evidence of disease, 19% (49 of 264) had abandoned treatment, 23% (61 of 264) had died during treatment, and 6% (15 of 264) had persistent disease., Conclusion: Survival of children with common and curable cancers is (significantly) below 50%. Almost half (42%) of the patients either abandoned treatment or died during treatment. Strategies to enable parents to complete treatment of their child and improved supportive care are needed. Such interventions may need to be given priority to improve the currently poor survival., (© 2020 Wiley Periodicals, Inc.)

Purpose: The aim of this study was to identify clinical factors predictive of time to central nervous system (CNS) lymphoma or death in patients with vitreoretinal lymphoma (VRL)., Design: Retrospective cohort study., Methods: Patients with VRL (n = 95 patients) from Januray 1, 1984 to July 30, 2018 were identified at a single ocular oncology center and records were retrospectively reviewed. Outcomes included Kaplan-Meier estimated time to CNS lymphoma and death., Results: There were 95 patients with VRL diagnosed at mean age 67 years, of which 70 patients had follow-up with the ocular oncology service. Mean time to CNS lymphoma in patients with isolated VRL was 56 months and did not differ by age, sex, bilateral ocular involvement, retinal infiltration, subretinal pigment epithelial (sub-RPE) infiltration, or treatment with prophylactic systemic chemotherapy (P > 0.05). Mean time to death was 66 months and did not differ when comparing those with CNS lymphoma diagnosed before VRL versus after VRL versus no CNS lymphoma at any time (67 vs 60 vs 64 months, P > 0.05). Presence of sub-RPE infiltration was associated with shorter mean time to death (46 vs 76 months, P = 0.04, odds ratio 1.9). Older patient age was associated with increased risk of death (odds ratio 1.0, P = 0.02). The mean time to death did not differ by sex, bilateral ocular involvement, retinal infiltration, timing of CNS or systemic lymphoma, or treatment with prophylactic systemic chemotherapy (P > 0.05)., Conclusions: Patients with VRL presenting with sub-RPE infiltration could have shorter mean survival time. Further studies are required to confirm these findings and determine whether sub-RPE infiltration is associated with more aggressive CNS lymphoma.

Background: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM)., Methods: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016)., Results: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030)., Conclusions: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM.

Purpose: To compare the clinical presentation and outcomes of retinoblastoma (RB) based on age at presentation., Methods: Retrospective comparative study of 1940 eyes of 1450 children with RB., Results: Presentation of RB with enlarged eyeball and eyelid swelling (2% and < 1% in ≤ 1 year, 4% and 2% in > 1-2 years, 7% and 2% in > 2-3 years, and 12% and 4% in > 3 years; p < 0.0001 and p = 0.05, respectively) is more common with increasing age. Based on the 8th edition of American Joint Committee Classification, T1 is more common in children younger than 1 year (27%), while T4 is more common in children > 3 years of age (20%) (p < 0.0001). Kaplan-Meier (KM) estimate at 1 and 5 years for globe salvage was 64% and 58% in children ≤ 1 year of age versus 30% and 20% in children > 3 years, respectively [Hazard ratio (HR) = 2.48; p < 0.0001], and KM estimate at 1 and 5 years for life salvage was 99% and 97% in children ≤ 1 year of age versus 89% and 78% in children older than 3 years, respectively (HR = 7.65; p < 0.0001)., Conclusion: Uncommon clinical features of RB including enlarged eyeball and eyelid swelling are more common with increasing age. Younger age at presentation with RB is associated with better prognosis including higher chances of life and globe salvage.

Purpose: Treatment abandonment because of enucleation refusal is a limitation of improving outcomes for children with retinoblastoma in countries with limited resources. Furthermore, many children present with buphthalmos and a high risk of globe rupture during enucleation. To address these unique circumstances, the AHOPCA II protocol introduced neoadjuvant chemotherapy with delayed enucleation., Patients and Methods: Patients with advanced unilateral intraocular disease (International Retinoblastoma Staging System [IRSS] stage I) were considered for upfront enucleation. Those with diffuse invasion of the choroid, postlaminar optic nerve, and/or anterior chamber invasion received six cycles of adjuvant chemotherapy (vincristine, carboplatin, and etoposide). Patients with buphthalmos and those with a perceived risk for enucleation refusal and/or abandonment were given two to three cycles of chemotherapy before scheduled enucleation followed by adjuvant chemotherapy to complete six cycles, regardless of pathology., Results: A total of 161 patients had unilateral IRSS stage I disease; 102 underwent upfront enucleation, and 59 had delayed enucleation. The estimated 5-year abandonment-sensitive event-free and overall survival rates for the group were 0.81 ± 0.03 and 0.86 ± 0.03, respectively. The 5-year estimated abandonment-sensitive event-free survival rates for patients undergoing upfront and delayed enucleation were 0.89 ± 0.03 and 0.68 ± 0.06, respectively ( P = .001). Compared with AHOPCA I, abandonment for patients with IRSS stage I retinoblastoma decreased from 16% to 4%., Conclusion: AHOPCA describes the results of advanced intraocular retinoblastoma treated with neoadjuvant chemotherapy. In eyes with buphthalmos and patients with risk of abandonment, neoadjuvant chemotherapy can be effective when followed by enucleation and adjuvant chemotherapy. Our study suggests that this approach can save patients with buphthalmos from ocular rupture and might reduce refusal of enucleation and abandonment.

Purpose: To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences., Patients and Methods: Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS)., Results: Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99)., Conclusion: Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.

Background/aims: Enucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on the current incidence of metastases and metastatic deaths in unilateral retinoblastoma from US centres., Methods: Retrospective chart review at five tertiary retinoblastoma centres in the USA for unilateral retinoblastoma patients treated with primary enucleation, 2007-2017, with > 1 year of follow-up or treatment failure., Results: Among 228 patients (228 eyes), there were nine metastases (3.9%) and four deaths (1.7%). The Kaplan-Meier estimate at 5 years for metastasis-free survival was 96% (95% CI, 94% to 99 %), and for overall survival was 98% (95% CI 96% to 100%). All metastases were evident within 12 months. Histopathology revealed higher risk pathology (postlaminar optic nerve and/or massive choroidal invasion) in 62 of 228 eyes (27%). Of these higher risk eyes, 39 received adjuvant chemotherapy. There were four subsequent metastases in this higher risk pathology with adjuvant chemotherapy group, with three deaths. Of the nine overall with metastases, seven (78%) showed higher risk pathology. All metastatic patients were classified as Reese-Ellsworth V and International Classification of Retinoblastoma Groups D or E. Initial metastases presented as orbital invasion in seven of nine cases., Conclusions: Primary enucleation for unilateral retinoblastoma results in a low rate of metastatic death, but is still associated with a 3.9% chance of metastases within a year of enucleation. Most but not all patients who developed metastases had higher risk histopathological findings., Competing Interests: Competing interests: No authors have any interests relevant to this study to disclose. Interests outside of the submitted work: JEL, JHF, CLS, MDY, JLB, KK, AKM, PRS and DHA have nothing to disclose. IJD reports other from Apexigen, personal fees from Bayer, grants and personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Eisai, personal fees from Ipsen, personal fees from Pfizer, grants from Genentech, outside the submitted work. AHS reports personal fees from Castle Biosciences, Inc, outside the submitted work. ABD reports grants from Research to Prevent Blindness, grants from Knights Templar Eye Foundation, grants from Alcon Research Institute, grants from Spectrum Pharmaceuticals, outside the submitted work., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3 months of age., Methods: This single-center retrospective study included 39 infants (42 eyes) aged ≤3 months who were diagnosed with unilateral or bilateral advanced intraocular retinoblastoma (group D and E eyes) and received IAC as primary or secondary treatment between June 2012 and February 2017. Based on each patient's therapeutic history and response to chemotherapeutic drugs, melphalan, topotecan, and/or carboplatin were used for IAC. The main outcomes included the technical success rate for IAC, survival rates, and adverse events., Results: In total, 29 and 13 eyes received IAC as primary and secondary treatments, respectively. Catheterization was successful in 136 of 137 procedures. All eyes in the secondary IAC group had previously received intravenous chemotherapy. The mean number of IAC sessions for each eye was 3 (range, 2-6). The 2-year ocular survival rates were 80.7% (95% confidence interval [CI], 58.9-91.7) in the primary IAC group and 91.7% (95% CI, 53.9-98.8) in the secondary IAC group. During the follow-up period, 1 patient with unilateral disease (group E) developed extraocular disease and died. The 2-year recurrence-free survival rates in the primary and secondary IAC groups were 71.9% (95% CI, 49.4-85.7) and 75.0% (95% CI, 40.8-91.2), respectively. During each catheterization procedure, the main complications included eyelid erythema (2.4%), fundus hemorrhage (11.9%), myelosuppression (7.7%), transient vomiting and hair loss (2.6%), and transient pancytopenia (2.6%). Prolonged complications included phthisis bulbi (19.0%), vision loss (19.0%), poor vision (9.5%), and cataract (2.4%). There was no case of stroke, neurological impairment, secondary malignant tumor, or metastasis., Conclusions: Our findings suggest that IAC, whether primary or secondary, is effective and fairly safe for the management of advanced retinoblastoma in infants aged < 3 months. However, adverse events related to intra-arterial injection and the visual outcomes cannot be neglected and require further investigation.

In this retrospective study of patients with overt orbital retinoblastoma, we evaluated minimally disseminated disease (MDD) in bone marrow and cerebrospinal fluid (CSF) using CRX and/or GD2 synthase as markers. Ten patients were evaluated-five (50%) at diagnosis and five upon relapse. MDD was detected in four cases (one in the bone marrow, two in the CSF, and in one case in both sites). All patients received chemotherapy and four received orbital radiotherapy. Seven patients relapsed or progressed and all of them died. Three patients remain in complete remission. There was no apparent correlation between MDD and the outcome., (© 2019 Wiley Periodicals, Inc.)

Primary vitreoretinal lymphoma (PVRL) is a subset of primary CNS lymphoma that presents as isolated ocular disease without brain involvement. Although ocular radiotherapy (RT) is an effective treatment for PVRL, the optimal treatment is uncertain. PVRL may later involve the brain in 56%-85% of patients. We report on 12 PVRL patients treated with a combination of bilateral RT and a systemic chemotherapy (CT) regimen containing high-dose methotrexate (M). Ten received RT (30-40 Gy) followed by CT, one received RT, and one was treated with intravitreal M; all achieved a complete response (CR). Three patients had tumor recurrence in the brain and received CT and one patient relapsed in the eye with a second recurrence in the brain. Three patients achieved CR-2 remain alive and one died of dementia. One died from recurrent CNS disease. With a median follow of 68 months (range, 17-154 months), median progression-free and overall survival have not been reached. Bilateral RT followed by M-based CT is an effective treatment for reducing CNS progression and prolonging survival., (© 2019 Wiley Periodicals, Inc.)

Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively. Among primary and concurrent VRL, median failure free survival (FFS), CNS relapse-free survival (CNS-RFS) and overall survival (OS) were: 1.8, 4.9, and 4.1 years, respectively; among PVRL, median FFS, CNS-RFS, and OS were: 2.6 year, Not Reached and 9.3 year, respectively. No CNS relapse occurred beyond 4 years in PVRL. Median OS for patients diagnosed between 1990 and 1999 vs between 2000 and 2018 was 1.5 vs 9.4 years, respectively (P = .0002). OS was significantly higher in PVRL, as compared with concurrent VRL (P = .04). Previous immunosuppression and poor performance status were predictive of worse outcome. In PVRL, a combined systemic and intraocular therapy showed higher FFS (P = .002) and CNS-RFS (P = .003), but no differences in OS. Among 18 secondary VRL, at a median follow-up of 1.1 year after vitreoretinal relapse, median FFS and OS were 0.3 and 1.3 years. An improvement in survival of VRL has been observed over the decades. PVRL should undergo combined systemic and intraocular chemotherapy to prevent CNS progression., (© 2018 Wiley Periodicals, Inc.)

Cancers occurring in children in Africa are often underdiagnosed, or at best diagnosed late. As a result, survival is poor, even for cancers considered 'curable'. With limited population-level data, understanding the actual burden and survival from childhood cancers in Africa is difficult. In this study, we aimed at providing survival estimates for the most common types of cancers affecting children aged 0-14 years, in three population-based Eastern African registries; Harare, Zimbabwe (Kaposi sarcoma, Wilms tumour (WT), non-Hodgkin lymphoma (NHL), retinoblastoma, and acute lymphocytic leukaemia (ALL)), Kampala, Uganda (Burkitt lymphoma, Kaposi sarcoma, WT, and retinoblastoma), and Nairobi, Kenya (ALL, retinoblastoma, WT, Burkitt lymphoma, and Hodgkin lymphoma). We included cases diagnosed within the years 1998-2009 and followed up till the end of 2011. We estimated the observed and relative survival at 1, 3, and 5 years after diagnosis. We studied 627 individual patient records. Median follow-up ranged from 2.2 months for children with Kaposi sarcoma in Harare to 30.2 months for children with ALL in Nairobi. The proportion of children lost to follow-up was highest in the first year after diagnosis. In Harare and Kampala, the 5-year relative survival was <46% for all cancer types. The 5-year relative survival was best for children in Nairobi, though with wider confidence intervals. Survival from childhood cancers in Africa is still poor, even for cancers with good prognosis and potential for cure. Supporting cancer detection, treatment, and registration activities could help improve survival chances for children with cancers in Africa., (© 2018 UICC.)

Purpose: To assess the effectiveness of intra-arterial chemotherapy (IAC), intravenous chemotherapy (IVC), and their combination in the management of group D retinoblastoma., Methods: This was a retrospective, interventional, comparative, and non-randomized clinical study, including all eyes with primarily treated group D retinoblastoma managed in a single institution from February 2010 to July 2016. Patient demographics, treatment modality (primary enucleation, intravenous chemotherapy, intra-arterial chemotherapy alone or intravenous, and intra-arterial chemotherapy), additional need for consolidation treatments or intravitreal melphalan (IVM) injections, and follow-up time were recorded. The main outcome measure was ocular survival rate after various treatment modalities., Results: Of 87 eyes of 83 consecutive cases, 9 eyes (10.3%) were primarily enucleated, 37 (42.6%) eyes received IVC, 30 (34.5%) eyes had IAC, and 11 (12.6%) eyes were treated with IVC followed by IAC. After a mean 81.1 ± 75.2 weeks of follow-up, enucleation rates were 56.8% in the IVC group, 23.3% in the IAC group, and 36.6% in the IVC + IAC group (p = 0.021). There was no significant difference of ocular survival estimates among these 3 groups at 2 or 5 years (p = 0.998, p = 0.986). With logistic regression analysis, age; gender; disease laterality; administration of IVM, TTT, or cryotherapy; mean dose of IVM; follow-up time; and number of IAC or IVC cycles were not significantly related to the enucleation rate (p > 0.05 for all variables)., Conclusions: Our experience showed that in group D patients, primary IAC achieved ocular survival in 76.7% of eyes, and less need for local consolidation treatments, whereas following primary IVC ocular survival was 43.2%.

Background: Vitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of large comparative clinical series. Combination of intravitreal and systemic chemotherapy is recommended in many reports. The aim of our retrospective study was to compare the survival rate and prognosis of patients with vitreoretinal lymphoma with and without CNS involvement., Methods: Twenty patients with vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare survival rates, we included 53 patients diagnosed with primary CNS lymphoma without vitreoretinal involvement between the years 2002and2011 from our haemato-oncology department., Results: The 5-year survival rate was estimated 71% in patients with vitreoretinal lymphoma in our observation. Significantly longer 5-year overall survival (P˂0.01) was observed in patients with vitreoretinal lymphoma compared with patients with primary CNS lymphoma without vitreoretinal involvement. Progression-free survival was almost equal in both groups of patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363). The relapse of lymphoma was frequent (50%-60%) with the median time to first relapse of 31 months. Combined treatment (local and systemic) in patients without CNS involvement significantly prolonged progression-free survival in our study (P˂0.05)., Conclusion: Combined treatment of primary vitreoretinal lymphoma significantly delays the relapse of lymphoma compared with local therapy alone. Intraocular involvement brings significant positive prognostic value when overall survival is compared., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To report the cosmetic outcome and late effects of enucleation and/or irradiation for retinoblastoma and to evaluate the role of orbital implants., Methods: Patients (age >4 years) enucleated and/or irradiated for retinoblastoma, visiting the hospital for routine follow-up (April 2013 to May 2015), were included in our cross-sectional study. Data were obtained via clinical records, questionnaires, physical measurements and standardized photographs. Two independent observers scored the cosmetic features: upper eyelid position, lower eyelid position, volume deficiency, and prosthesis motility and overall cosmetic appearance., Results: A total of 195 patients participated. Ptosis was seen in 45 (28.3%) patients, lower lid sagging in 45 (28.3%). Both complications were associated with the orbital implant; ptosis being more common with increasing implant size (5.6% without implant, 16.7% with small implant, 37.1% with medium implant and 76.9% with large implant) and lower lid sagging being more common in patients without implant (20% with implant versus 37.5% without). Volume loss of the superior sulcus was seen in 107 sockets (66.9%), most frequent in additionally irradiated patients (χ 2 (2) = 42.7, p < 0.001) and in patients without implant (χ 2 (2) = 11.92, p = 0.003). Prosthesis motility was better in patients with orbital implant, regardless of the size., Conclusion: Minor late and potentially treatable effects were seen in patients with implant. Larger sized implants were associated with a higher incidence of ptosis; implant size did not affect subjective outcome with respect to volume or prosthetic motility. Treatment with EBRT had a less favourable outcome., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The feasibility and results of intraarterial chemotherapy, also termed ophthalmic artery chemosurgery (OAC), for retinoblastoma in less developed countries have seldom been reported., Procedure: A retrospective evaluation of a program of OAC in Argentina from 2010 to 2015., Results: Ninety-seven eyes from 81 patients (61 bilateral) were analyzed. In 35 eyes, OAC was given as primary therapy and in 62 it was used for the treatment of tumors with partial response or those relapsing after systemic chemoreduction with focal therapy or external-beam radiotherapy. Twenty-two primarily treated eyes had group D and 13 groups B/C. A total of 400 procedures were carried out. Chemotherapy used included combinations of melphalan, carboplatin, and topotecan. There was no mortality associated with OAC. Toxicity included fever and neutropenia in five (1.25%), hypotension and bradycardia during anesthesia in two and femoral thrombosis in one, eyelid edema in nine, and neutropenia or thrombocytopenia in 28 cycles. With a median follow-up of 48.7 months (range 12-79), the 3-year probability of event-free survival (pEFS) (enucleation and/or radiotherapy were considered events) was comparable for patients who received first-line therapy and those treated at relapse (0.65 vs. 0.63, P = 0.5). In the former, the pEFS was 0.91 and 0.43 for groups B/C and D, respectively (P = 0.01). Two patients died of extraocular dissemination after refusal of enucleation., Conclusions: OAC was feasible with low toxicity. pEFS improved in all groups compared to the previous experience with systemic chemotherapy reducing the use of radiotherapy. The overall mortality associated with OAC is comparable to our previous experience with systemic chemoreduction., (© 2018 Wiley Periodicals, Inc.)

Background: Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015., Procedure: The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French-African Paediatric Oncology Group., Results: Eighty-eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months-5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event-free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8-81.2%) and 59% (95% CI 47.9-69.5%), respectively, with a median follow-up of 3.7 years (0.1-5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource-limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival., (© 2018 Wiley Periodicals, Inc.)

Importance: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management., Objective: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria., Design, Setting, and Participants: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017., Interventions: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles., Main Outcomes and Measures: Probability of event-free survival (extraocular relapse and death from any cause were considered events)., Results: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death)., Conclusions and Relevance: Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.

Purpose: To report associations between disease- and treatment-related variables and rates of recurrence-free survival and ocular survival in eyes treated with ophthalmic artery chemosurgery (OAC) for retinoblastoma., Design: Pre-post study., Subjects: All eyes treated with OAC for retinoblastoma at Memorial Sloan Kettering Cancer Center between May 2006 and February 2017., Methods: This retrospective review included 452 retinoblastoma eyes treated with OAC. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS), progression-free survival (PFS) and ocular survival (OcS), and Cox regression was used to estimate hazard ratios. Eyes treated in the pre-intravitreous chemotherapy era were analyzed separately from eyes treated in the intravitreal era., Main Outcome Measures: Recurrence-free survival, ocular survival, associations with risk of recurrence., Results: Disease and treatment characteristics were recorded over a median 23.6 month follow-up. One-year OcS, PFS and RFS were 96% (95% CI 93-99%), 88% (95% CI 88-94%) and 74% (95% CI 67-81%) in the pre-intravitreal era and 96% (95% CI 94-99%), 93% (95% CI 89-96%) and 78% (95% CI 72-83%) in the intravitreal era, respectively. Presence of vitreous seeds was associated with increased risk of recurrence in the pre-intravitreal era but not in the intravitreal era. Longer time interval between OAC sessions was associated with increased risk of recurrence and majority OAC access via the ophthalmic artery was associated with decreased risk of recurrence in both eras., Conclusions: Approximately a quarter of eyes initially treated with ophthalmic artery chemosurgery develop recurrent disease, with the majority of recurrences within the first year following completion of OAC. Despite this, these eyes have a very good chance of salvage. In eyes with vitreous seeds at presentation, intravitreal injections are useful in minimizing future vitreous recurrence. Eyes that receive the majority of drug infusions via non-ophthalmic artery routes or greater interval between OAC are more likely to recur and might warrant closer monitoring., Competing Interests: The authors have declared that no competing interests exist.

Purpose: In retinoblastoma, adjuvant chemotherapy after enucleation is given in eyes with histopathological high-risk features (HRFs) to reduced mortality. Anterior chamber seeds (AC seeds) on histopathological evaluation are a contentious finding. This study attempts to determine the effect of AC seeds on the survival rate., Methods: This is a retrospective case record review. Eyes were divided into four groups: those with neither AC seeds nor HRFs, those with only HRFs, those with only AC seeds, and those with both HRFs and AC seeds. The groups were compared for demographic and clinical features and survival curves were plotted for each., Results: For the 212 eyes included in the study, mean age was 30.5 ± 36.8 months. Children with only AC seeds were significantly older (75.3 ± 94.6 months) (P = 0.004). Chemotherapy was administered in 81 (38.2%) of 212 eyes; 16 (13.7%) of 117 eyes without HRF and in 65 (68.4%) of 95 eyes with HRFs (P < 0.001). The survival rate at 1, 3, and 5 years was the highest for the group with only AC seeds, although the difference was not statistically significant., Conclusions: We conclude that AC seeds do not, by themselves, constitute an independent risk factor for metastasis. These children need not be treated with immediate adjuvant chemotherapy, but, instead, can be followed with regular screening for metastasis. However, AC seeds are seen in only a small proportion of enucleated eyes. A larger study would better validate our study results.

Background: Retinoblastoma poses a substantial burden in developing countries. We conducted this study to assess the effect of implementing a multidisciplinary approach and standardized protocols for treating pediatric patients with retinoblastoma at the Children's Cancer Hospital Egypt (CCHE)., Materials and Methods: In January 2011, the CCHE implemented standardized protocols for the diagnosis, treatment, and reporting of retinoblastoma cases. The hospital also introduced a new retinoblastoma management algorithm and data analysis system. In this study, we compared the pathologic features, tumor invasiveness, reporting, and survival of 276 pediatric patients who underwent enucleations of 290 eyes before or after the implementation of the retinoblastoma protocols., Results: Time to enucleation (indicating time needed for decision taking) decreased significantly within the neoadjuvant chemotherapy group for intraocular disease after January 2011 (68.7 ± 48 weeks vs. 47.3 ± 28.3 weeks; p < 0.05). Mean optic nerve stump length increased from 5.6 mm in the earlier period to 7.2 mm in the later period (p = 0.004). The overall quality of pathology reporting also improved during the later period. The probability of 3-year survival was significantly higher for patients during the later period (94.2% vs. 79.2%; p = 0.018)., Conclusions: The implementation of standardized protocols and a multidisciplinary approach improved reporting; discrepancies in disease classification and the amount of missing data were reduced; and quality measures and prognostic capabilities of the team were substantially improved. Such established data-driven practice supports faster decision making to enucleate diseased eyes and save patients' lives through providing measurable indicators.

Objective: To summarize the clinical features, treatment and prognosis of retinoblastoma (RB) patients in distant metastasis stage. Methods: Retrospective case series study. Clinical data of 24 cases (30 eyes) with diagnosis of distant metastasis stage RB were collected in pediatrics department of Beijing Tongren Hospital affiliated with Capital Medical University, from September 2005 to December 2013. In these cases, including 11 male cases and 13 female cases, the treatment age ranged from 7 months to 9 years with the median of 26 months. There were 18 unilateral cases (12 cases of right eye and 6 cases of left eye) and 6 bilateral cases. All cases were treated with surgery, chemotherapy and radiotherapy. The adverse reaction, blood routine and biochemical routine were monitored dynamically and regularly during treatment. The clinical manifestations and auxiliary examination were combined to evaluate the therapeutic effect. Determining the prognosis with death and survival, the survival curve and the median survival time were calculated by the product limit method. Results: The results of pathologic examination of 13 cases showed 11 cases of optic nerve involvement, 6 cases of optic nerve and choroid involvement, 1 case of post laminar involvement, 1 case of cornea and conjunctiva involvement. The most common metastatic site was central nerve system (CNS) (23 cases), followed by orbital involvement (10 cases). Other metastatic sites included bone (9 cases), bone marrow (1 case), pleura (1 case) and lymph node (1 case). 23 patients with CNS metastasis underwent systemic chemotherapy and intrathecal injection. The toxicity and side effects of radiotherapy and chemotherapy were evaluated and classified as grade I-II. Those adverse effects were tolerated by all cases. Followed up to December 31, 2015, all patients with CNS metastasis died and the median survival time was 6 months. Only 1 patient without CNS metastasis disease-free survived for 64 months. Conclusions: The most common metastasis site of RB was CNS. The overall prognosis of RB with distant metastasis was poor, in spite of given combined treatment mainly including surgery, chemotherapy and radiotherapy. But the prognosis of RB patients without CNS metastasis in distant metastasis stage was better than with CNS metastasis. (Chin J Ophthalmol, 2017, 53: 121-126) .

Background: Surgical removal of one or both eyes has been the most common way to treat children with retinoblastoma worldwide for more than 100 years. Ophthalmic artery chemosurgery (OAC) was introduced 10 years ago and it has been used as an alternative to enucleation for eyes with advanced retinoblastoma. The purpose of this report is to analyze our 9-year experience treating advanced retinoblastoma eyes with OAC., Materials and Methods: Single-arm retrospective study from a single center of 226 eyes with eyes of retinoblastoma patients with advanced intraocular disease defined as both Reese-Ellsworth (RE) "Va" or "Vb" and International Classification Retinoblastoma (ICRb) group "D" or "E" (COG Classification). Ocular survival, patient survival, second cancers, and electroretinography (ERG) were assessed., Results: Ocular survival at five years for these advanced eyes was 70.2% (95% confidence interval, 57.3%-79.8%). When eyes were divided into groups either by RE classification or ICRb, no significant differences in ocular survival were seen. Ocular survival was significantly better in naïve compared to non-naïve eyes (80.2% vs 58.4%, p = 0.041). The ERG distribution was very similar before and after OAC treatment for the patient population that did not receive intravitreal chemotherapy. Three patients (1.5%) have developed metastatic retinoblastoma (previously reported) and were successfully treated (no deaths)., Conclusion: Using OAC for advanced eyes (the majority of such eyes have been enucleated in the past) enables 70% 5-year ocular survival. Treated eyes have a similar ERG distribution before and after treatment. No patient has died of metastatic retinoblastoma.

Importance: Fatal metastatic relapse may occur in children with retinoblastoma and high-risk pathologic features (HRPFs). Minimal dissemination (MD) may be an additional tool for risk estimation. The use of cone-rod homeobox (CRX) transcription factor messenger RNA for MD evaluation in metastatic retinoblastoma was previously reported, but no data in nonmetastatic cases with HRPFs are available., Objectives: To evaluate whether MD is detectable in patients with nonmetastatic retinoblastoma and to assess its prognostic effect on disease-free survival (DFS)., Design, Setting, and Participants: This single-institution cohort study of patients with nonmetastatic retinoblastoma and HRPFs used prospectively defined inclusion criteria and a sampling strategy to procure bone marrow (BM) and cerebrospinal fluid (CSF) samples from May 1, 2007, through October 31, 2013. Median follow-up was 38 months (range, 8-89 months). Survival analysis was closed in December 2015, and no further updates were made after that point., Interventions: The study evaluated CRX messenger RNA by quantitative polymerase chain reaction in BM and CSF at diagnosis and follow-up. In 14 patients, GD2 synthase was used instead of CRX for CSF evaluation. Patients were treated under uniform guidelines., Main Outcomes and Measures: Metastatic relapse., Results: The study included 96 children (median age at study inclusion, 26 months; range, 1-168 months; 46 male [47.9%]; 50 female [52.1%]) with nonmetastatic retinoblastoma and HRPFs (isolated massive choroidal invasion in 14, postlaminar optic nerve invasion in 51 [26 with concomitant massive choroidal and 13 with scleral invasion], 12 with scleral invasion without postlaminar optic nerve invasion, and 7 with tumor at the resection margin of the optic nerve) were evaluated at the time of primary or secondary enucleation. Minimal dissemination was detected in 9 patients (7 BM samples and 2 CSF samples) and was associated with extension beyond the resection margin of the optic nerve and scleral involvement, but only the former was independently associated (adjusted odds ratio, 57.0; 95% CI, 4.8-678.2; P = .001). In addition, MD occurred in 8 of the 43 International Intraocular Retinoblastoma Classification group E eyes with glaucoma (18.6%) and in 8 of 80 (10%) and 1 of 16 children (6.3%) who underwent primary or secondary enucleation, respectively. Children with MD had a 3-year DFS of 0.78 compared with 0.98 in those without MD (95% CI for the difference in DFS, 0.17-0.23; P = .004)., Conclusions and Relevance: These findings identified a high-risk population of children with retinoblastoma and HRPFs with MD. Because the number of events was small, these results, which suggest that children with International Intraocular Retinoblastoma Classification group E retinoblastoma and glaucoma have a higher risk of MD at diagnosis, should not be considered definitive at this time.

Purpose: To compare the clinical effects of different cycles of carboplatin, etoposide, and vincristine (CEV) regimens of adjuvant chemotherapy in postenucleation high-risk patients with IRSS Stage I retinoblastoma (RB)., Methods: A retrospective analysis of 53 RB patients hospitalized in the Zhongshan Ophthalmic Center of Sun Yat-sen University was performed. All patients had unilateral involvement, received enucleation treatment, were diagnosed as RB by pathology, and had high-risk pathological factors. Patients either refused postoperative chemotherapy or received three or six cycles of CEV regimen chemotherapy. The clinical information, treatment, and results of patients in all groups were compared., Results: A total of 19 cases refused postenucleation chemotherapy, 18 cases received three cycles, and 16 cases received six cycles of the CEV regimen chemotherapy. The 5-year disease-free survival rate and the overall survival (OS) rate in the chemotherapy group were higher than those in the non-chemotherapy group (97.1% vs. 63.2%, p = 0.001) and were not different between the three-cycle chemotherapy group and the six-cycle chemotherapy group (94.4% vs. 100%, p = 0.35)., Conclusion: After eye enucleation for patients with high-risk unilateral RB, the CEV regimen chemotherapy was associated with a higher survival rate. The three-cycle CEV regimen adjuvant chemotherapy was effective and is expected to replace the six-cycle CEV regimen chemotherapy.

Purpose: Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma., Patients and Methods: Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma., Results: The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect., Conclusion: The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed., (© 2016 by American Society of Clinical Oncology.)

Purpose of Review: Retinoblastoma is the most common primary ocular malignancy in children. Although currently retinoblastoma has an excellent survival rate in developed countries, hereditary retinoblastoma survivors as well as those with a history of radiation therapy as children are at an increased risk for second primary tumors (SPTs), and specifically, for orbital sarcomas. Despite the known increased risk for SPTs in retinoblastoma survivors and the associated morbidity and mortality, no screening or treatment guidelines exist., Recent Findings: Understanding of retinoblastoma tumorigenesis and genomic expression has expanded significantly, and treatment has evolved with a shift away from radiotherapy. Until the last two decades, however, radiation was the therapy of choice for patients with bilateral disease. Because both hereditary retinoblastoma and radiation are independent risk factors for the development of SPTs such as sarcomas and these SPTs are often fatal, appropriate surveillance for retinoblastoma survivors is crucial., Summary: As a result of the excellent survival rates for retinoblastoma patients, it is important to: recognize the risk of sarcoma, particularly in patients with hereditary retinoblastoma and/or prior radiation therapy; establish a screening protocol, such as the one proposed, to maximize early detection; and discuss and develop treatment guidelines for high-risk patients. Future directions of research for these patients will involve the development of molecularly targeted agents and the use of proton radiotherapy.

Objective: Report on the 7-year experience with bilateral ophthalmic artery chemosurgery (OAC-Tandem therapy) for bilateral retinoblastoma., Design: Retrospective, single institution study., Subjects: 120 eyes of 60 children with bilateral retinoblastoma treated since March 2008., Methods: Retrospective review of all children treated at Memorial Sloan Kettering with bilateral ophthalmic artery chemosurgery (Melphalan, Carboplatin, Topotecan, Methotrexate) delivered in the same initial session to both naïve and previously treated eyes., Main Outcome Measures: Ocular survival, metastatic disease, patient survival from metastases, second cancers, systemic adverse effects, need for transfusion of blood products, electroretinogram before and after treatment., Results: 116 eyes were salvaged (4 eyes were enucleated: 3 because of progressive disease, 1 family choice). Kaplan Meier ocular survival was 99.2% at one year, 96.9% at 2 and 3 years and 94.9% for years 4 through 7. There were no cases of metastatic disease or metastatic deaths with a mean follow-up of 3.01 years. Two children developed second cancers (both pineoblastoma) and one of them died. Transfusion of blood products was required in 3 cases (4 transfusions), 1.9%. Two children developed fever/neutropenia requiring hospitalization (0.95%). ERGs were improved in 21.6% and unchanged after treatment in 52.5% of cases (increase or decrease of less than 25μV)., Conclusions: Bilateral ophthalmic artery chemosurgery is a safe and effective technique for managing bilateral retinoblastoma-even when eyes are advanced bilaterally, and if both eyes have progressed after systemic chemotherapy. Ocular survival was excellent (94.9% at 8 years), there were no cases of of metastatic disease and no deaths from metastatic disease, but children remain at risk for second cancers. In 21.6% of cases ERG function improved. Despite using chemotherapy in both eyes in the same session, systemic toxicity was low.