Differences in Childhood Growth Parameters Between Patients With Somatic and Heritable Retinoblastoma.

Purpose: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb. Methods: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005. Results: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile. Conclusions: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

Risk factors associated with abandonment of care in retinoblastoma: analysis of 692 patients from 10 countries.

BACKGROUND: Rates of care abandonment for retinoblastoma (RB) demonstrate significant geographical variation; however, other variables that place a patient at risk of abandoning care remain unclear. This study aims to identify the risk factors for care abandonment across a multinational set of patients. METHODS: A prospective, observational study of 692 patients from 11 RB centres in 10 countries was conducted from 1 January 2019 to 31 December 2019. Multivariate logistic regression was used to identify risk factors associated with higher rates of care abandonment. RESULTS: Logistic regression showed a higher risk of abandoning care based on country (high-risk countries include Bangladesh (OR=18.1), Pakistan (OR=45.5) and Peru (OR=9.23), p<0.001), female sex (OR=2.39, p=0.013) and advanced clinical stage (OR=4.22, p<0.001). Enucleation as primary treatment was not associated with a higher risk of care abandonment (OR=0.59, p=0.206). CONCLUSION: Country, advanced disease and female sex were all associated with higher rates of abandonment. In this analysis, enucleation as the primary treatment was not associated with abandonment. Further research investigating cultural barriers can enable the building of targeted retention strategies unique to each country.

The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study.

BACKGROUND/OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.

Lacrimal Sac Tumors: A Case Series.

Objective: The aim of the study was to describe the clinical presentation, management strategies, and outcomes in a case series of primary lacrimal sac tumors. Methods: This retrospective study was conducted in Sheikh Fajilatunnessa Mujib Eye Hospital and Training Institute, Bangladesh, from July 1 to December 31, 2020, and included all patients who were evaluated, treated, and followed up for at least 6 months from January 2013 to October 2020. One patient developed a recurrence of the adenocarcinoma of the lacrimal sac after 1 year of primary treatment. Patients' demographic data were analyzed and reviewed from published articles on lacrimal sac tumors. We assessed patients clinically, followed by radiological evaluation. We also analyzed the biopsy technique, treatment modality, and recurrence. An oncologist reviewed all patients to prepare a plan for adjuvant treatment. Results: Ten patients with lacrimal sac tumors were included in this study. Swelling in the medial canthal region was the most common presenting feature (100%), followed by epiphora (60%) and pain (30%). Open biopsy was preferred over fine-needle aspiration biopsy. Incisional biopsy or complete excisional biopsy was performed for all suspected malignancies. Malignant tumors were found in 7 (70%) cases, and benign tumors in 3 (30%) cases. Non-Hodgkin's lymphoma (NHL) (40%) was the most common malignant lacrimal sac tumor. Mucosa-associated lymphoid tissue lymphoma was 75%, and diffuse large B-cell lymphoma was 25% among the cases of NHL. Patients with epithelial malignancy were treated with external beam radiation therapy, while NHL patients were treated with chemotherapy (CHOP regimen). Recurrence was noted in 1 case (10%) of epithelial malignancy after 1 year of treatment. Conclusion: Successful management of lacrimal sac tumors requires a high index of suspicion, as these are fatal tumors, often misdiagnosed as dacryocystitis. Nonepithelial malignancies are more predominant than epithelial malignancies, and hematolymphoid tumors are most frequent.

Clinicopathological Analysis and Surgical Outcome of Eyelid Malignancies: A Study of 332 Cases.

BACKGROUND: Eyelid tumours are common in our ophthalmic practice. Malignancy cases account only for one-fourth of all eyelid tumours. The most aggressive eyelid malignancy is sebaceous gland carcinoma, but its occurrences are rare in western countries. We found sebaceous gland carcinoma is as common as basal cell carcinoma in our clinical practices. Hence, it is essential to build awareness about the more aggressive eyelid malignancies to reduce morbidity and mortality. AIM: To assess the relative frequency of eyelid malignancies in the Bangladesh population, state their clinical features and outcome of management strategies and build awareness about the more aggressive eyelid malignancies to reduce morbidity and mortality. METHODS: This was a retrospective case series study of 332 patients in Bangladesh. This study analyzed all the recorded data of the histologically proven primary eyelid malignancies and followed them up for at least six months from 2014 to 2019 (6 years). All patients were managed by surgical excision with tumor-free margins verified on histopathology, either the frozen section or excision biopsy with 2-3 mm microscopic view of normal tissue followed by eyelid reconstruction. Computer-based statistical software SPSS was used for the analysis, and an appropriate test of significance (chi-square) was used for the statistical analysis. RESULTS: Sebaceous gland carcinoma (SGC) was the highest in occurrence, at 42%, followed by 38% basal cell carcinoma (BCC), 18% squamous cell carcinoma (SqCC), and 02% malignant melanoma (MM). The mean age at presentation of SGC, BCC, SqCC, and MM were 57.41 years, 62.56 years, 64.73 years, and 59.28 years, respectively. Female (59%) was slightly more preponderance over the male (41%) for SGC than other malignancies. Pigmentation was associated with malignant melanoma (100%) and BCC (81%). Statistically, a significant difference was found between eyelid malignancies, including location, size, pigmentation, recurrence, and invasiveness. The recurrence rate was low lower in the patients who underwent frozen section biopsy (3%) for margin clearance than those who underwent excision biopsy (21.5%) in the follow-up time. Conjunctival map biopsy (8%) was performed as an essential tool for excluding the pagetoid spread of SGC. A new reconstruction method named triangular-shaped musculocutaneous tail flap was performed in 33 (11%) patients to reconstruct the moderate eyelid defect following local resection. CONCLUSION: Sebaceous gland carcinoma (SGC) was the highest occurrence found to be the highest occurrence among all eyelid malignancies in Bangladesh. SGC is more aggressive and the recurrence rate was higher than BCC and SqCC.

Defining High-risk Retinoblastoma: A Multicenter Global Survey.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

The Effects of Breastfeeding on Retinoblastoma Development: Results from an International Multicenter Retinoblastoma Survey.

The protective effects of breastfeeding on various childhood malignancies have been established but an association has not yet been determined for retinoblastoma (RB). We aimed to further investigate the role of breastfeeding in the severity of nonhereditary RB development, assessing relationship to (1) age at diagnosis, (2) ocular prognosis, measured by International Intraocular RB Classification (IIRC) or Intraocular Classification of RB (ICRB) group and success of eye salvage, and (3) extraocular involvement. Analyses were performed on a global dataset subgroup of 344 RB patients whose legal guardian(s) consented to answer a neonatal questionnaire. Patients with undetermined or mixed feeding history, family history of RB, or sporadic bilateral RB were excluded. There was no statistically significant difference between breastfed and formula-fed groups in (1) age at diagnosis (p = 0.20), (2) ocular prognosis measures of IIRC/ICRB group (p = 0.62) and success of eye salvage (p = 0.16), or (3) extraocular involvement shown by International Retinoblastoma Staging System (IRSS) at presentation (p = 0.74), lymph node involvement (p = 0.20), and distant metastases (p = 0.37). This study suggests that breastfeeding neither impacts the sporadic development nor is associated with a decrease in the severity of nonhereditary RB as measured by age at diagnosis, stage of disease, ocular prognosis, and extraocular spread. A further exploration into the impact of diet on children who develop RB is warranted.

Lag Time between Onset of First Symptom and Treatment of Retinoblastoma: An International Collaborative Study of 692 Patients from 10 Countries.

BACKGROUND: The relationship between lag time and outcomes in retinoblastoma (RB) is unclear. In this study, we aimed to study the effect of lag time between onset of symptoms and diagnosis of retinoblastoma (RB) in countries based on their national-income and analyse its effect on the outcomes. METHODS: We performed a prospective study of 692 patients from 11 RB centres in 10 countries from 1 January 2019 to 31 December 2019. RESULTS: The following factors were significantly different among different countries based on national-income level: age at diagnosis of RB (p = 0.001), distance from home to nearest primary healthcare centre (p = 0.03) and mean lag time between detection of first symptom to visit to RB treatment centre (p = 0.0007). After adjusting for country income, increased lag time between onset of symptoms and diagnosis of RB was associated with higher chances of an advanced tumour at presentation (p < 0.001), higher chances of high-risk histopathology features (p = 0.003), regional lymph node metastasis (p < 0.001), systemic metastasis (p < 0.001) and death (p < 0.001). CONCLUSIONS: There is a significant difference in the lag time between onset of signs and symptoms and referral to an RB treatment centre among countries based on national income resulting in significant differences in the presenting features and clinical outcomes.