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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 (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.)

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.

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.

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.

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.

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.)

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.)

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.

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.

Background: Retinoblastoma (Rb) is the most common intraocular tumor diagnosed in children in Brazil. However, detailed information is lacking regarding patient clinical demographics. This study aimed to determine the clinical profile of patients with Rb who were treated in a public university hospital in southern Brazil from 1983 to 2012., Methods: Patients' medical records were reviewed to retrospectively identify patients with a principal diagnosis of Rb. Rb was classified as hereditary or non-hereditary. Clinical staging was reviewed by an ophthalmologist. Statistical analysis was performed using SPSS., Results: Of 165 patients with a diagnosis of Rb during this period, 140 were included in the study. Disease was unilateral in 65.0 % of patients, bilateral in 32.9 %, and trilateral in 2.1 %. The mean age at onset of the first sign/symptom was 18.1 month, and 35.7 % of patients were diagnosed during the first year of life. The most common presenting signs were leukocoria (73.6 %) and strabismus (20.7 %). The mean age at diagnosis was 23.5 months, and time to diagnosis was 5.4 months. In patients with clinical features of hereditary Rb, both onset of the first sign/symptom and diagnosis were at an earlier age than in patients without these features (12.3 vs 21.6 months [P = 0.001] and 15.9 vs 28.0 months [P < 0.001], respectively). However, there was no significant difference in overall survival between the two groups. Ocular stage at diagnosis was advanced in 76.5 % (Reese V) and 78.1 % (International Classification D or E). Of patients with unilateral and bilateral disease, 35.2 % and 34.8 %, respectively, had extraocular disease at diagnosis; 10.7 % had metastatic disease at diagnosis. Enucleation was observed in 88.1 % and exenteration in 11.9 % of patients; 93.6 % patients were followed until 2012, and 22.9 % relapsed. Overall survival was 86.4 %., Conclusions: Most Rb diagnoses are still diagnosed in advanced stages of the disease, considerably reducing overall survival time and the rate of eye and vision preservation.

Background: The transcriptional co-activator, TAZ, is an important effector of the Hippo pathway and is critical for the development of human cancers. However, the expression and prognostic significance of TAZ in retinoblastoma is currently unclear., Methods: TAZ expression was examined in 43 retinoblastoma samples by immunohistochemistry. The relationship between TAZ expression and the clinicopathological features of retinoblastoma was also analyzed. Cox regression and Kaplan-Meier survival analyses were used to identify the prognostic factors for retinoblastoma patients. Finally, the effects of TAZ on cell proliferation were explored through lentivirus-mediated downregulation of TAZ in retinoblastoma cells., Results: TAZ was highly expressed in retinoblastoma tissues and was associated with regional lymph node classification (P = 0.013), largest tumor base (P = 0.045), and differentiation (P = 0.019). Moreover, patients with high TAZ expression had shorter overall survival (OS), progression-free survival (PFS), loco-regional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) time than patients with low TAZ expression (P < 0.05). Multivariate analysis showed that high TAZ expression was an important prognostic factor for retinoblastoma patients. In addition, downregulation of TAZ expression significantly suppressed tumor cell proliferation by blocking the transition of the cell cycle from G1 to S phase., Conclusions: Our findings suggest that the high expression of TAZ plays a significant role in retinoblastoma's aggressiveness, and predicts poor prognosis for patients with retinoblastoma.

Background/aim: The aim of this study was to investigate the potential correlation between clinical characteristics and prognosis of patients with retinoblastoma (Rb)., Materials and Methods: This retrospective study included 314 Rb patients. Clinical data including laterality of eyes, sex, age, presenting signs, lag time, and survival were recorded and analyzed., Results: Leukocoria is the most common clinical presentation of Rb. Patients with isolated leukocoria had shorter lag time and exhibited a high survival rate (85%, 5 years). Patients with strabismus and blurred vision, and who were older and had longer lag time, exhibited an excellent survival rate (100% and 92.3%, respectively, 5 years). Patients with exophthalmos had the longest lag time and the lowest survival rate (17.8%, 5 years). The 5-year survival rate of patients with a lag time of 6 months was 84.7%, which was significantly higher than that of patients with a lag time of > 6 months (64.7%)., Conclusion: Leukocoria, strabismus, and blurred vision are mild clinical manifestations of Rb that are associated with better disease prognosis, whereas exophthalmos is an indicator of poor prognosis. Long lag time is a risk factor for the survival of Rb, which can be avoided. Early detection and treatment can greatly improve the survival of Rb patients.

Background: Retinoblastoma (RB) is rare, albeit the most common primary intraocular malignancy among children. To elucidate the true incidence, trend and survival, we studied incidences and trends of retinoblastoma in a large population with long-term follow-up using data from 3 population-based cancer registries., Objective: To describe the incidence, trends and survival of RB between 1990 and 2009 in Khon Kaen, Songkhla and Chiang Mai, Thailand., Materials and Methods: We sourced the data from the cancer registries in Khon Kaen, Songkhla and Chiang Mai on children with retinoblastoma, diagnosed between 1990 and 2009. Retinoblastoma was defined as per the International Classification of Disease for Oncology version 3 using the code 9510/3. Incidence was analyzed using the standard method with the criteria of the International Association of Cancer Registries. The Kaplan-Meier method was applied to calculate cumulative survival. Trends were calculated using the log rank test., Results: We identified 75 cases of children between 0 and 15 years of age diagnosed with RB (Khon Kaen 31, Chiang Mai 20, Songkhla 24). Males and females were equally affected. The most common age group was 0-4 years. The morphological verification of the disease was 90.7%. The respective ASR in Khon Kaen, Chiang Mai and Songkhla was 4.4, 4.0 and 4.6 per million; for which the overall ASR for all 3 areas was 4.3 per million. The respective trend in incidence was 4, 2.8, 5.8 and 5.4 during 1990-4, 1995-9, 2000-4 and 2005-9. Overall, incidence trended gradually upward by 2% annually. The respective survival rate in Khon Kaen, Chiang Mai and Songkhla was 50, 40 and 75% (differences not significantly different at p=0.14) and the overall survival for all centers was 60%., Conclusions: Over the last two decades, the incidence and overall survival of retinoblastoma has increased. The ASRs and survival in Thailand were less than those in resource-rich countries.

CD117 (C-kit) is thought to play an important role in tumourigenesis. There are limited data in the literature concerning C-kit expression in retinoblastoma. To date, no immunohistochemical studies have been performed to assess the possible association of C-kit with vascular endothelial growth factor (VEGF) in retinoblastoma. This study was designed to investigate C-kit and VEGF immunoexpression in retinoblastoma, their relationship with prognostic parameters as well as the correlation between them. A prospective immunohistochemical study was conducted on 56 retinoblastoma cases. Patients who had received preoperative chemotherapy were excluded. Positive C-kit and VEGF immunoreactivity was observed in 48.2% and 76.8% of retinoblastoma cases respectively. No C-kit immunostaining was seen in the adjacent uninvolved retina. However, VEGF expression was detected within its vasculature. Retinoblastomas with combined pattern of tumour growth revealed a highly significant positive C-kit expression (P = 0.002) compared to cases with endophytic or exophytic growths. Also, positive C-kit expression was statistically higher in cases with optic nerve invasion (P = 0.001) and choroidal invasion (P ≤ 0.01) compared to negative cases. A highly significant positive VEGF expression was detected in cases with optic nerve invasion (P = 0.013) compared to negative cases. Moreover, a highly significant positive correlation was detected between C-kit and VEGF expression (P = 0.006). C-kit is a feature of more aggressive retinoblastomas, with increased expression in tumours spreading beyond the retina. Moreover, VEGF is vastly expressed in retinoblastoma and is associated with optic nerve invasion. Both C-kit and VEGF may represent potential therapeutic targets for retinoblastomas.

Background: More invasive retinoblastoma, characterized by increased morbidity and mortality, with lower rates of eye salvage and higher rates of extraocular dissemination, seems more prevalent in resource-poor countries. The relationship of diagnostic delay (lag time) and sociodemographic factors on the extent of disease at diagnosis has not been examined separately for unilateral and bilateral retinoblastoma., Methods: At diagnosis, consenting parents of 179 Mexican children with retinoblastoma were interviewed about initial symptoms and household demographic characteristics. Clinical presentation was classified using St. Jude's, International Staging System (ISS), and International Intraocular Retinoblastoma Classification (IIRC) criteria. Lag time (delay between noting symptoms and diagnosis) and sociodemographic factors were examined as predictors for higher stage at diagnosis and overall survival (OS)., Results: In bilateral disease, lag time predicts stage at diagnosis using St. Jude's, and ISS criteria (P < 0.005 in multivariate regression), and OS (P < 0.05, Cox hazards), but not extent of intraocular disease (by IIRC). In unilateral disease, lag time predicts neither extent of disease (using ISS, St Jude's, and IIRC), nor OS. Indicators of prenatal poverty, including lower maternal education and the presence of dirt flooring in the home, predict more advanced disease by IIRC for bilateral retinoblastoma, and for unilateral by ISS, and St Jude's (P < 0.001) as well as OS (P < 0.05)., Conclusion: These results suggest unilateral and bilateral retinoblastoma differs in factors governing progression and extraretinal extension, possibly reflecting underlying biologic heterogeneity., Impact: This demonstrates differing effect of social factors on extent of intra- and extraocular disease depending on laterality with implications for screening strategies., (©2014 AACR.)

Background: Retinoblastoma is a rare type of cancer that usually develops in early childhood. If left untreated it can cause blindness and even death. The aim of this study is to determine sociodemographic and clinical features of retinoblastoma patients and also to determine the treatment pattern and outcome in Malaysia., Materials and Methods: Data for this study were retrieved from the Retinoblastoma Registry of the National Eye Database (NED) in Malaysia. Hospital Kuala Lumpur, Hospital Umum Kuching, Sarawak and Hospital Queen Elizabeth, Kota Kinabalu were the major source data providers for this study. Data collected in the registry cover demography, clinical presentation, modes of treatment, outcomes and complications., Results: The study group consisted of 119 patients (162 eyes) diagnosed with retinoblastoma between 2004 and 2012. There were 68 male (57.1%) and 51 (42.9%) female. The median age at presentation was 22 months. A majority of patients were Malays (54.6%), followed by Chinese (18, 5%), Indians (8.4%), and indigenous races (15.9%). Seventy six (63.8%) patients had unilateral involvement whereas 43 patients had bilateral disease (36.1%). It was found that most children presented with leukocoria (110 patients), followed by strabismus (19), and protopsis (12). Among the 76 with unilateral involvement (76 eyes), enucleation was performed for a majority (79%). More than half of these patients had extraocular extension. Of the 40 who received chemotherapy, 95% were given drugs systemically. Furthermore, in 43 patients with bilateral involvement (86 eyes), 35 (41%) eyes were enucleated and 17 (49%) showed extraocular extension. Seventy-two percent of these patients received systemic chemotherapy. The patients were followed up 1 year after diagnosis, whereby 66 were found to be alive and 4 dead. Sixteen patients defaulted treatment and were lost to follow-up, whereas follow-up data were not available in 33 patients., Conclusions: Patients with retinoblastoma in this middle-income Asian setting are presenting at late stages. As a result, a high proportion of patients warrant aggressive management such as enucleation. We also showed that a high number of patients default follow-up. Therefore, reduction in refusal or delay to initial treatment, and follow-up should be emphasized in order to improve the survival rates of retinoblastoma in this part of the world.

Introduction: Retinoblastoma is a malignant tumor of the embryonic neural retina. It is the most common intraocular tumor of childhood. It is a disease of early childhood with 80% cases diagnosed before the age of 4 years. The median age at diagnosis is 2 years. Bilateral cases are diagnosed earlier (median at 12 months and unilateral median age at 24 months). The incidence of retinoblastoma is approximately 1 in 15000-18000 live births in developed countries. The aim of the research is to study the clinical pathological features, treatment and survival of children with retinoblastoma over ten years., Methods: A retrospective hospital based study was conducted from March 1998 to February 2008. Gender, age, clinical presentation, pathology reports, treatment, follow-up and outcome were recorded at time of diagnosis., Results: A total of 42 children with retinoblastoma (85.7 % unilateral, 14.3% bilateral), with 50% having optic nerve involvement were studied. The most common presenting signs were extraoccular (28.6%), proptosis (23.8%), leukoria (23.8%), phthisis bulbi (16.7%), and strabismus (7.1%). The age at presentation ranged from 6-120 months with mean age of 46.6 months. The male to female ratio was 1.1:1.Two-thirds presented between 2-5 yrs, followed by 12-24 months (23.8%). Majority of children had poorly differentiated retinoblastoma (62 %), followed by well differentiated (28.6%), and moderately differentiated (9.5%). CEV based protocol used to treat, and over-all 10 yrs survival was 23.8 %, death 19 %, and lost to follow-up or left against medical advice 57.2%., Conclusions: Despite severe resource limitation, pediatric oncology unit has been successfully treating retinoblastoma with the success rate of 23.8%.

Purpose: To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma., Methods:   From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes)., Results: Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively., Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To identify constitutional alterations of the retinoblastoma 1 gene (RB1) in two cohorts of Brazilian patients with retinoblastoma and to analyze genotype-phenotype associations., Methods: Molecular screening was carried out by direct sequencing of the 27 RB1 exons and flanking regions in blood DNA of 71 patients with retinoblastoma and 4 relatives with retinoma, and with multiplex ligation-dependent probe amplification (MLPA) in 21 patients. The presumed impact of nucleotide substitutions on the structure of the retinoblastoma protein (pRB) was predicted by Polymorphism Phenotyping-2 (PolyPhen-2). Kaplan-Meier and log-rank test were used for estimating 60-month survival rates., Results: One hundred two nucleotide substitutions were detected, 92 substitutions in 59 patients with retinoblastoma and 10 substitutions in 4 individuals with retinoma. Eight substitutions were novel. The majority of substitutions were intronic (86.2%). More than one substitution was present in 37.3% of patients. Twenty-one duplications and 11 deletions were found in 12 patients; some of which with both types of alterations. Duplications/deletions were found in four patients lacking constitutional alterations when analyzed by sequencing, and in eight patients carrying one or more polymorphic intronic substitutions. The global 60-month survival rate in patients was 91.8% (Confidence Interval95% = 85.0 - 99.1). Significant, lower survival rates were found in extraocular presentation (81.0%) versus intraocular tumors (P = 0.014), first enucleation after 1 month following diagnosis (80.9%) versus earlier first enucleation (P = 0.020), and relapse (100.0%) versus absence of relapse (P = 0.0005)., Conclusions: Fifteen substitutions (4 intronic and 11 exonic) were identified as probably or likely pathogenic. Four of these 11 exonic substitutions were novel. Survival rates, however, were not affected by presence of these probably or likely pathogenic alterations, most of which not found in patients with retinoblastoma from other Latin American countries. These differences might be related to the different ethnic composition of the Latin American cohorts. Portuguese Abstract.

Context: Advanced cases of retinoblastoma are treated with chemoreduction followed by enucleation. Further adjuvant therapy is recommended in patients with known pathologic risk factors (PRFs)., Objectives: To determine the PRFs in enucleated specimens after chemoreduction and their association for adverse events of recurrence, metastasis, or death., Design: This was a retrospective study of 77 enucleation specimens from patients treated between January 2000 and September 2008 with prior chemoreduction that were accessioned in the pathology department of a tertiary referral cancer center with an average follow-up of 24 months. Various PRFs were noted and their association with the development of an adverse event was recorded., Results: Of 77 patients, (male to female ratio, 51∶26), the incidence of overall PRF was 51.9%, and retrolaminar optic nerve invasion (32.5%), optic nerve cut margin (12.9%), massive choroidal invasion (26%), scleral invasion (23.4%), vitreous seedings (44.2%), and anterior segment invasion (20.8%). Undifferentiated tumor (>60%) was seen in 60.3% of cases (41 of 68 patients with differentiation available). Adverse event occurred in 18 of 72 patients with available follow-up (25%). Retrolaminar optic nerve invasion, optic nerve cut margin involvement, and scleral invasion were independent prognostic factors predicting the occurrence of an adverse event. Undifferentiated tumor (>60%) was a significant risk factor in univariate analysis, which is the unique feature in this study., Conclusions: Classic PRF with the addition of a predominant presence from the undifferentiated component were associated with adverse outcomes in retinoblastoma treated with anterior chemotherapy. The latter may represent chemoresistant clones and more intensive adjuvant chemotherapy may be warranted in these patients.

Objective: Little is known about the incidence of secondary neoplasms among survivors of retinoblastoma in Japan. The objective of our study was to analyze the cumulative incidence rate of secondary neoplasms following retinoblastoma and to investigate the risk factors of developing secondary neoplasms., Methods: We conducted a retrospective cohort study of 754 retinoblastoma patients who visited the National Cancer Center Hospital in Tokyo between 1964 and 2007. The cumulative incidence rate curves were drawn using the competing risk method and compared with the Gray's test. Using competing risk regression analysis, multivariate analysis estimated the subdistribution hazard ratio of factors related to the development of secondary neoplasms., Results: The median length of follow-up was 108 months (0-594 months). Twenty-one (2.8%) patients developed 23 secondary neoplasms in total. The cumulative incidence rates of secondary neoplasms after retinoblastoma treatment were 2.4% at 10 years after diagnosis, 4.3% at 20 years, 6.4% at 30 years and 19.1% at 40 years. Ten patients (1.3%) died and 723 (95.9%) were alive without developing secondary neoplasms. The subdistribution hazard ratios of hereditary retinoblastoma and external beam irradiation were 4.85 (95% confidence interval = 0.74-31.85) and 4.76 (95% confidence interval = 0.69-33.09), respectively., Conclusions: We demonstrated the cumulative incidence rate of secondary neoplasms following retinoblastoma in Japan. The subdistribution hazards ratios of hereditary retinoblastoma and external beam irradiation were high but not significant because of statistical power. The long-term follow-up of retinoblastoma survivors is warranted to understand secondary neoplasm risk.

Purpose: To determine the therapeutic effect of oncolytic adenovirus H101 on retinoblastoma in vitro and in vivo., Methods: The expression of coxsackievirus-adenovirus receptor (CAR) in human retinoblastoma cell line HXO-RB(44) was determined by RT-PCR, Western blot, immunofluorescence, and immunocytochemistry staining. Appropriate multiplicity of infection was determined using flow cytometry in retinoblastoma cells with green fluorescent protein-expressing adenovirus (AdGFP). The viability of HXO-RB(44) cells treated with H101 or AdGFP was measured using a cell counting kit-8-based procedure. Viral proliferation in vitro was measured by end point dilution titration and real-time PCR. Cell cycle and apoptotic activity of HXO-RB(44) were analyzed by flow cytometry. NOD-SCID mice bearing retinoblastoma xenografts were treated with intratumoral injection of H101, AdGFP, or PBS. Tumor volume and survival time were recorded. Immunohistochemistry for adenoviral fiber protein and Western blot for adenoviral Hexon protein of retinoblastoma xenografts were performed to evaluate H101 virus replication in vivo., Results: HXO-RB(44) cells expressed CAR and were sensitive to adenoviral infection. HXO-RB(44) cells treated with H101 had reduced cell viability compared with AdGFP-treated cells (P < 0.01). Abundant replication of H101 in HXO-RB(44) cells resulted in G(2)/M-phase arrest and finally tumor cell lysis, but the apoptosis pathway was not activated. Tumor-bearing mice treated with H101 had reduced tumor burdens and prolonged survival times compared with PBS and AdGFP controls (both P < 0.01). Immunohistochemical and Western blot examination revealed widespread replication of H101 within the tumor., Conclusions: These results suggest that H101 effectively inhibits the growth of retinoblastoma cells in vitro and in mice and may serve as a novel therapy for retinoblastoma.

Purpose: To describe the incidence and survival rate of patients with retinoblastoma in Taiwan over a 25-year period, from 1979 to 2003., Methods: Cases of retinoblastoma have been reported to the Taiwan National Cancer Registry (TNCR) since 1979. Retinoblastoma data from 1979 to 2003 were retrieved from the TNCR databank for analysis of both the incidence and survival rate. Trends in the incidence rate were estimated by calculating the annual percentage change (APC)., Results: From 1979 to 2003, a total of 380 patients (182 [47.9%] females) with retinoblastoma were identified. Of the 380 cases, 359 patients (94.5%) were diagnosed before 5 years of age. The average annual age-standardized incidence rate was 4.45 per million in children under 10 years of age and 8.58 per million in children under 5 years of age. There was a significant increasing trend in the incidence rate over the study period with an APC of 2.3% (P=0.035). Before the implementation of Taiwan's National Health Insurance (NHI) Program in 1995, the mean age at diagnosis was 4.8+/-13.3 years and the 5-year survival rate was 74.7%. After implementation of the NIH Program, the mean age at diagnosis decreased to 1.6+/-2.1 years (P<0.001) and the 5-year survival rate increased to 84.7% (P=0.063)., Conclusions: We report the first population-based study on retinoblastoma in Taiwan. There was a significant increasing trend in the incidence rate from 1979 to 2003. Since the implementation of Taiwan's NHI, the mean diagnostic age decreased.

Background: Subsequent malignant neoplasms are a major cause of premature death in survivors of hereditary retinoblastoma. Radiotherapy further increases the risk of death. Mortality information is limited among long-term survivors who were irradiated for hereditary retinoblastoma., Methods: We examined cause-specific mortality among 1854 retinoblastoma survivors who were diagnosed from January 1, 1914, through December 31, 1996, at two US institutions. Standardized mortality ratios (SMRs) were calculated by use of US mortality data to estimate expected numbers of deaths. The relative rates (RRs) of mortality due to subsequent malignant neoplasms associated with multiple risk factors were evaluated with Poisson regression models. Cumulative mortality from subsequent malignant neoplasms was calculated by treating other causes of death as competing risks., Results: A total of 151 deaths due to subsequent malignant neoplasms occurred among 1092 hereditary retinoblastoma survivors (SMR = 35, 95% confidence interval [CI] = 30 to 41) compared with 12 deaths among 762 nonhereditary retinoblastoma survivors (SMR = 2.5, 95% CI = 1.3 to 4.4). In this extended follow-up of retinoblastoma survivors, we found no evidence of excess mortality from non-neoplastic causes compared with the general population. However, excess mortality from subsequent malignant neoplasms (particularly sarcomas, melanomas, and cancers of the brain and other parts of the nervous system) among hereditary retinoblastoma survivors extended beyond 40 years after retinoblastoma diagnosis. The additional 13 years of follow-up since our last mortality study revealed a previously unreported increased risk of death due to cancers of the corpus uteri (primarily sarcomas) and confirmed the previously reported elevated risk of death from lung cancer among hereditary retinoblastoma survivors. Among hereditary and nonhereditary retinoblastoma survivors, the relative rates of mortality from subsequent malignant neoplasm were higher in those who had been treated with radiotherapy than in those who had not. Cumulative mortality from subsequent malignant neoplasms at 50 years after retinoblastoma diagnosis was 25.5% (95% CI = 20.8% to 30.2%) for hereditary retinoblastoma survivors and 1.0% (95% CI = 0.2% to 1.8%) for nonhereditary retinoblastoma survivors., Conclusions: The temporal patterns of site-specific excess risks of subsequent malignant neoplasms in retinoblastoma survivors should inform screening programs designed for the early detection and treatment of subsequent malignant neoplasms.

Purpose: Chemotherapy resistance is a problem in the treatment of advanced retinoblastoma (RB). Since basic fibroblast growth factor (bFGF) is a survival factor for neural precursor cells, bFGF was evaluated as a growth and chemoresistance factor in RB., Methods: bFGF expression was analyzed in the LH-betaTag transgenic mouse model of RB and human RB cell lines by immunofluorescence, RT-PCR, and Western blot. Proliferation and apoptosis (TUNEL) assays were performed., Results: bFGF levels significantly increased during tumorigenesis in transgenic RB, as a function of tumor status (P = 0.005). PCR and confocal microscopy confirmed that the human cell lines and primary tumors expressed bFGF. bFGF was localized to vascular and tumor cells and rarely to glial cells. Exogenous 18-kDa bFGF induced proliferation in two RB cell lines (WERI and Y79). Western blot analysis demonstrated 34-, 22-, and 18-kDa isoforms in transgenic RB and both cell lines. In TUNEL assays, chemoresistance to carboplatin-induced apoptosis was observed in the Y79 line, which expressed a higher ratio of high (34 kDa)- to low-molecular-weight bFGF isoforms, compared with the WERI line. Similar to other bFGF tumor studies, exogenous low-molecular-weight (18 kDa) bFGF (1 ng) significantly enhanced carboplatin-induced apoptosis in the more chemosensitive WERI, but not the chemoresistant Y79 line., Conclusions: RB tumors produce significant amounts of bFGF, and the differential production and response to isoforms of bFGF may have implications for invasive tumor growth and chemoresistance.

Context: Retinoblastoma is the most common malignant intraocular tumor in children. It has been shown that adjuvant therapy following enucleation in patients with high-risk histopathologic features significantly decreases the mortality. We describe the association of extensive necrosis of tumor and intraocular structures with 2 of the major risk factors: optic nerve invasion and choroidal invasion. This may alert the pathologist who makes the observation of extensive necrosis to carefully search for histologic features associated with adverse outcome., Objective: To determine whether extensively necrotic retinoblastoma is associated with high-risk histologic prognostic factors for metastatic disease and patient survival., Design: Retrospective case series. Forty-three eyes of 43 patients with retinoblastoma who underwent enucleation between 1990 and 2001 were evaluated. Medical records, histopathology specimens, pathology reports, and clinical photographs were reviewed. Tumors were designated as exhibiting extensive necrosis if more than 95% of tumor cells and intraocular tissues were necrotic. The main outcome measure was the association of extensive tumor necrosis with 3 high-risk histopathologic features: extraocular extension, optic nerve invasion, or choroidal invasion. Metastatic disease, patient survival, and associations with pathologic findings were also analyzed., Results: Optic nerve head invasion (P < .001), post-lamina-cribrosal invasion (P < .001), and choroidal invasion by tumor (P = .004) were observed more frequently in eyes with extensive necrosis compared with eyes without extensive necrosis. Two of the 11 patients with extensively necrotic intraocular retinoblastoma died from metastatic disease (P = .06). None of the 32 patients without extensive necrosis developed metastatic disease or died., Conclusions: Extensive ocular tissue and tumor necrosis is associated with histologic high-risk prognostic factors for tumor metastasis and mortality.

A significant risk of lung cancer was identified among hereditary, but not nonhereditary, retinoblastoma (Rb) patients. Tobacco use was investigated to determine whether differences in smoking prevalence might explain the lung cancer excess and to characterize smoking patterns in adult survivors of Rb. Subjects were 441 hereditary and 395 nonhereditary 1-year survivors of Rb, age >or=18 years, who responded to a telephone survey about current health behavior, including tobacco use. Response rates were 76% for hereditary and 73% for nonhereditary survivors. We compared patterns and predictors of current tobacco use among hereditary and nonhereditary survivors with other childhood cancer survivor studies and the U.S. population. Hereditary Rb survivors currently smoke cigarettes significantly less frequently than nonhereditary survivors (16. 8% versus 24.3%), although among current smokers, age at smoking initiation (17 years old) and average cigarettes (1.5 packs) smoked daily are similar. Predictors of current and ever cigarette smoking include nonhereditary Rb, older age, being female, less education, and use of other tobacco products. Rb survivors smoke cigarettes significantly less than the U.S. population (rate ratio, 0.63; 95% confidence interval, 0.5-0.8 for males; rate ratio, 0.75; 95% confidence interval, 0.6-0.9 for females), but Rb survivors have comparable smoking rates with other childhood cancer survivors. Smoking did not account for the increased risk of lung cancer among hereditary Rb patients, and this may point to an enhanced sensitivity to the carcinogenic effects of tobacco. Adult survivors of Rb should be encouraged to stop smoking.

Background: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico., Methods: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained., Results: The authors analysed 500 cases; age range was 0-182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up., Conclusions: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB.