Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: a survey by the European Retinoblastoma group (EURbG)

Introduction: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond natural limits of the eye may lead to metastatic disease which is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. Method: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma group (EURbG) network. Extended information were gathered via personal Email communication. Results: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. Conclusion: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Histopathological Features of Group E Retinoblastoma Eyes after Upfront Enucleation

Purpose: To study histopathological features of eyes with intraocular Group E retinoblastoma primarily treated by enucleation at a tertiary care centre in Karachi, Pakistan. Study Design: Retrospective histopathological study. Place and Duration of Study: Department of Ophthalmology, Patel Hospital, Karachi, January 2012 to August 2019. Methods: Seventy five eyes of children diagnosed with Group E retinoblastoma, on clinical examination, examination under general anaesthesia along with MRI and then enucleated were examined histopathologically after being primarily enucleated. Histological features were enlisted for the presence of choroidal invasion, extent of optic nerve invasion, anterior chamber involvement, scleral and extra-scleral invasion along with tumour differentiation. Demographic variables (age at presentation, gender, laterality of the disease, median follow-up) and the histopathological features of tumour along with high risk features were assessed using SPSS version 24. Results: Out of 75 eyes, 48 (64%) eyes showed high risk histopathological features including post lamina cribrosa involvement, choroidal invasion, scleral involvement, anterior chamber involvement (angle, iris, ciliary body). All high risk features were significantly more in the poorly differentiated group of tumours. All patients showing high risk features were given post enucleation systemic chemotherapy accordingly. Conclusion: By identifying the histopathological pattern and high risk features, we can decrease the chances of metastasis, recurrence, mortality and morbidity of these children which pose an overwhelming physical, psychological, social and financial burden on our society as a whole. Further large, multi-centre prospective studies can provide with a better understanding about the high risk features and histopathological patterns of retinoblastoma in our region. Key Words: Retinoblastoma, Enucleation, Chemotherapy.

The Impact of Eye Size in Retinoblastoma

Background: The typical imaged findings of retinoblastoma are an intraocular tumor with intratumoral calcification. Normal eye size is a supported finding of retinoblastoma. In practice, more than just a few cases had an altered eye size. Objective: To evaluate the effect of eye size in retinoblastoma. Materials and Methods: The present study included 47 patients with 54 diseased eyes. Twenty-seven patients underwent enucleation with histopathological results. The axial lengths (AL) and equatorial diameters (ED) were measured in both diseased and normal eyes. The imaging characteristics, tumor volume, and histopathological findings were recorded and analyzed. Results: The results showed no statistically significant differences between AL, ED, and calculated eye volumes (EV) between diseased and normal eyes. Anterior chamber depths were statistically shallower in retinoblastoma eyes (p<0.001). EV was weakly associated with tumor volumes. Large eye size was significantly related to choroidal invasion, massive choroidal invasion, scleral invasion, and optic nerve invasion in pathology (p=0.04, 0.03, 0.02, and 0.04, respectively). Conclusion: There were no statistically significant differences of eye size parameters in the eyes with retinoblastoma when compared to the normal eyes. Large eye size and large tumor volume are significantly related to invasive histopathological results. Keywords: Retinoblastoma, Intraocular tumor, Eye size, Tumor volume, Histopathology, Neoplasm invasion

Epidemiology and clinical features of retinoblastoma

Introduction: Retinoblastoma (RB) is a prototype of heritable cancers. It is more common in the lower socioeconomic strata. Delayed presentation significantly reduces the overall outcome. We have analyzed the epidemiological and clinical data of children who were diagnosed with RB between the years 2009 and 2014. Aim: RB being a disease of the poor, delayed presentation is common due to lack of awareness. We have analyzed the epidemiological profile of our patients and tried to establish the link between delayed presentation and the presence of high-risk features. High-risk features are associated with higher chance of metastasis and poor rates of vision salvage in RB. Methodology: Data were collected in a retrospective manner from the patient case files retrieved from the Medical Records Department, Kidwai cancer Institute. The data were analyzed using Excel and SPSS software (IBM Corp. released 2016, IBM SPSS statistics software for Mac OS, version 24, IBM Corp., Armonk, NY). Results: A total of 53 patients were diagnosed with RB in the years 2009–2014. There was a male predominance with 1.2:1 incidence. Bilateral RB was present in 21 cases. The mean age of children with bilateral RB was 2.1 years, against 1.5 years in unilateral cases. High-risk features such as optic nerve invasion, choroidal invasion, intracranial extension, and orbital involvement were found in 12, 6, 5, and 5 eyes, respectively. Bone marrow involvement was detected in 5% and lung metastasis in 2%. Intracranial involvement was found in 10.4% and cerebrospinal fluid positivity in 15%. Children with high-risk features had a significant delay in presentation in comparison to those without high-risk features (P = 0.035). Conclusion: Incidence of metastatic disease and delayed presentation is still high in developing countries. Routine eye examination during vaccination visits can ensure early diagnosis and appropriate referral in many of these children.

Clinicopathological Findings of Retinoblastoma: A 10-Year Experience from a Tertiary Hospital in Kampala, Uganda

Background. Retinoblastoma (RB) is one of the most common cancers occurring in young children in sub-Saharan Africa. The incidence rate reported in the literature is 9,000 new cases per year, which corresponds to 1 in 15,000 births. This study aimed at analyzing the clinicopathological findings in children with RB in Uganda. Purpose. The purpose of this study was to describe and analyze the clinicopathological findings in the patients with RB. Design. This was a cross-sectional analytical study involving 234 eyeball surgical specimens from 214 patients with RB diagnosed between January 2006 and December 2015. Results. The mean age of the patients was 27.8 months (SD = 21.413, range: 1–132 months). More than half of the cases, 50.9%, presented with leucokoria. Invasion of choroid, sclera, anterior chamber, and optic nerve was found in 26.5% (n = 58), 51.2% (n = 88), 26.2% (n = 45), and 29.2% (n = 49), respectively. Twenty-six percent (n = 56) of the cases with intraocular tumour were at stage I and all patients with metastasis 4.7% (n = 11) had stage IV. The correlation between postlaminar optic nerve invasion and massive choroidal invasion was statistically significant (P=0.002). Also, there was a statistical significance difference between metastasis and postlaminar invasion (P=0.004). Conclusion. The majority of children with RB in Uganda present clinically with leucokoria, and their parents or guardians seek medical intervention at a later stage. Moreover, there was a noticeably significant lag period for the patients to begin treatment after the diagnosis was done.

Metastases and death rates after primary enucleation of unilateral retinoblastoma in the USA 2007–2017

Background/aimsEnucleation 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.MethodsRetrospective 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.ResultsAmong 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.ConclusionsPrimary 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.

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features

Purpose: To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. Methods: A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Results: Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Conclusions and relevance: Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.