Familial Retinoblastoma Research Articles

Navigating familial retinoblastoma in Kenya: A mother's journey.

Navigating familial retinoblastoma in Kenya: A mother's journey.

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

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

Late metastasis in bilateral familial retinoblastoma and review of literature

A 5-year-old female with bilateral familial retinoblastoma (Group A, Group C) was treated with systemic chemotherapy and three cycles of intra-arterial chemotherapy. She was being followed closely and had no evidence of intraocular recurrence for 4 years. She developed isolated femoral metastasis 5 years after initial diagnosis and was treated with high-dose chemotherapy and stem cell transplant. This case emphasizes the need for metastatic monitoring for low-grade retinoblastoma and points toward delayed tumor latency.

Investigation of the methylation changes in the promoter region of RB1 gene in retinoblastoma: Unraveling the epigenetic puzzle in retinoblastoma

Retinoblastoma is an infrequent neoplasm that arises during childhood from retinal nerve cells and is attributed to the biallelic inactivation of the RB1 gene. In conjunction with anatomical anomalies, it is widely acknowledged that epigenetic modifications play a significant role in the pathogenesis of cancer. The association between methylation of the RB1 gene promoter and tumor formation has been established; however, there is currently no scholarly evidence to substantiate the claim that it is responsible for the inheritance of retinoblastoma. The initial hypothesis posited for this work was that familial retinoblastoma disease would be similarly observed in cases with RB1 promotor gene methylation, akin to RB1 mutations. The RB1 gene promoter region was subjected to methylation screening using real-time PCR in individuals diagnosed with familial retinoblastoma but lacking RB1 mutations. The study involved a comparison of the germline methylation status of the RB1 gene in the peripheral blood samples of 50 retinoblastoma patients and 52 healthy individuals. The healthy individuals were carefully selected to match the retinoblastoma patients in terms of age, sex, and ethnicity. The data obtained from both groups were subjected to statistical analysis. The study revealed that the methylation level in a cohort of 50 individuals diagnosed with retinoblastoma and 52 healthy control participants was determined to be 36.1% and 33.9%, respectively. As a result, there was no statistically significant disparity observed in RB1 promoter methylation between the patient and control groups (p = 0.126). The methylation of the promoter region of the RB1 gene in familial retinoblastoma does not exert any influence on the hereditary transmission of the disease.

Newly Recognized Genetic Tumor Syndromes of the CNS in the 5th WHO Classification: Imaging Overview with Genetic Updates.

The nervous system is commonly involved in a wide range of genetic tumor-predisposition syndromes. The classification of genetic tumor syndromes has evolved during the past years; however, it has now become clear that these syndromes can be categorized into a relatively small number of major mechanisms, which form the basis of the new 5th edition of the World Health Organization book (beta online version) on genetic tumor syndromes. For the first time, the World Health Organization has also included a separate chapter on genetic tumor syndromes in the latest edition of all the multisystem tumor series, including the 5th edition of CNS tumors. Our understanding of these syndromes has evolved rapidly since the previous edition (4th edition, 2016) with recognition of 8 new syndromes, including the following: Elongator protein complex-medulloblastoma syndrome, BRCA1-associated protein 1 tumor-predisposition syndrome, DICER1 syndrome, familial paraganglioma syndrome, melanoma-astrocytoma syndrome, Carney complex, Fanconi anemia, and familial retinoblastoma. This review provides a description of these new CNS tumor syndromes with a focus on imaging and genetic characteristics.

Clinical analysis of 2790 children with retinoblastoma: a single-center experience in China.

In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17years. The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted. The median age of the participants was 28.3months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62months (95% CI = 67.70-93.54). The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis.

Prenatal Diagnosis of Retinoblastomas: A Scoping Review.

The objective of this review is to explore the prenatal diagnosis of retinoblastoma and the recommended screening practices. An electronic literature search on prenatal diagnosis of retinoblastoma was conducted on the PubMed database. Publications within the last 20 years that matched the inclusion criteria were selected. The literature search included the following keywords: retinoblastoma, prenatal, diagnosis, screening, and associated synonyms to increase search sensitivity. Nine studies were included for investigation and extracted to identify prenatal diagnostic and screening techniques for retinoblastoma, their associated impact, and the target population that should receive prenatal screening for retinoblastoma. Familial retinoblastoma has an autosomal inheritance pattern and 90% penetrance. Therefore, future parents with a family history of retinoblastoma are strongly advised to get tested for retinoblastoma (Rb) gene mutations; if one of the parents is positive for a mutated allele of the RB1 gene, there is a 45% chance that their child will inherit a mutated allele of the retinoblastoma gene, rendering the allele non-functional in all of the cells of the individual and predisposing the child to a higher risk of developing retinoblastoma as well as other secondary cancers. Thus, prenatal screening and diagnosis of retinoblastoma is crucial for early diagnosis and optimal treatment. Prenatal testing for retinoblastoma in high-risk families is important for everyone in the family. For the parents, prenatal screening has been shown to improve their family planning decisions and psychological well-being as they can mentally prepare beforehand and make informed decisions. More importantly, these practices have shown to yield better treatment and vision outcomes in the newborn.

Retinoblastoma outcomes: a global perspective

Retinoblastoma outcomes: a global perspective

Recurrence and new tumor development after frontline intravenous chemotherapy for retinoblastoma: Risk factors and treatment results.

To evaluate the risk factors leading to recurrence and new tumor (NT) development in patients with retinoblastoma after intravenous chemotherapy (IVC) and to review the treatment outcomes. The records of 166 retinoblastoma cases (having 246 affected eyes) who underwent six-cycle IVC (vincristine, etoposide, and carboplatin) as primary treatment between October 1999 and August 2020 were reviewed retrospectively. The mean ages at presentation were 9.0 (median: 8.0) and 9.2 (median: 8.5) months in cases with recurrence and NTs respectively. Recurrence was detected in 40 (16.3%) eyes, NTs in 29 (11.8%), and both recurrence/NTs in 24 (9.8%). The mean time elapsed till recurrence and NT was 10.7 months. Multivariable analysis showed that the factors predictive of recurrence were largest tumor base diameter (LTBD) >12 mm (p = 0.039) and presence of subretinal seeds at diagnosis (p = 0.043). Multivariable risk factors for the development of NTs were bilateral familial retinoblastoma (p = 0.001) and presence of subretinal seeds at diagnosis (p = 0.010). Mean follow-up was 80.1 (median: 72.5) months. By Kaplan-Meier analysis, the 1-, 3-, and 6-year recurrence and NT rates were 21.2%, 28.1%, and 28.7% and 14.9%, 22.6%, and 23.9% respectively. The most common treatment methods used for recurrent and/or NTs included cryotherapy, transpupillary thermotherapy, and intra-arterial chemotherapy. Enucleation was eventually required in 24/93 (25.8%) eyes. No patient developed metastasis. Development of recurrence and/or NT after IVC was noted in 38% of all retinoblastoma eyes. Bilateral familial disease, LTBD >12 mm, and presence of subretinal seeds at baseline were risk factors for recurrence and NTs in this study.

Fundus Examination of 23,861 Newborns by Digital Imaging in Ningbo.

Purpose To perform fundus examinations of full-term and premature infants to identify common congenital ocular diseases and determine the incidence and additional risk factors in Ningbo, China. Methods Fundus examinations were performed on newborns between January 2017 and July 2020 in Ningbo using a RetCam3 or PanoCam LT wide-field digital imaging system. The neonates' birth weight, gestational age, gender, delivery mode, oxygen intake, and other conditions were recorded. We compared the incidence of ocular abnormalities in both full-term newborns and premature infants. Results There were 23,861 newborns in this study comprising 12,605 (52.8%) male and 11,256 (47.2%) female infants, 20,938 full-term babies, and 2,923 premature babies. The average gestational age was 37.9 ± 5.6 weeks, and the average birth weight was 3,189 ± 417 g. Overall, we found ocular abnormalities in 6,645 (27.8%). The most common abnormality in full-term newborns was retinal hemorrhage (RH), which we found in 3,827 (18.3%) cases. Other diseases identified included familial exudative vitreoretinopathy (FEVR), retinoblastoma (RB), and congenital cataracts. The delivery method had a significant impact on the incidence of neonatal RH (P < 0.001). Retinopathy of prematurity (ROP) was observed in 617 newborns accounting for 21.1% of all screened premature infants. Logistic analysis showed that gestational age and birth weight were important risk factors for ROP (P < 0.001). For treatable diseases, such as ROP, FEVR, congenital cataract, glaucoma, and RB, early identification allows for active treatment or referral to a specialized hospital for further treatment. Conclusion Early examination and prompt treatment of ocular disorders in newborns are important to avoid lifelong visual impairment. Eye examinations should be performed during the neonatal period and at regular follow-up visits.

At What Age Could Screening for Familial Retinoblastoma Be Discontinued? A Systematic Review.

Simple SummaryOffspring of patients with heritable retinoblastoma have a high risk of developing retinoblastoma themselves. Ophthalmological screening from birth in at-risk children ensures early detection and increases survival. As not every at-risk child develops retinoblastoma it should be determined until what age familial retinoblastoma can occur, so that ophthalmological screening could safely be stopped at that age. Extended screening beyond this age would result in unnecessary patient burden and costs. By systematically searching the medical literature for latest age at diagnosis in this population, we ascertained that among adequately screened patients the oldest age at diagnosis is 48 months. Therefore, screening for familial retinoblastoma can safely be stopped at four years of age.The aim of this systematic review is to assess the latest age at diagnosis for detection of familial retinoblastoma in order to evaluate at what age screening of at-risk children could be discontinued. Extended screening beyond this age would result in unnecessary patient burden and costs. However, discontinuing screening prematurely would have the adverse effect of missing tumors. We performed a literature search (PubMed, Embase, CINAHL and the Cochrane Library) up until February of 2021 and systematically included studies where patients had a family history of retinoblastoma, a known age at diagnosis, and who were ophthalmologically screened for retinoblastoma from birth. A total of 176 familial retinoblastoma patients from 17 studies were included in this review. Based on 48 months of age being the latest age of diagnosis, ophthalmological screening for familial retinoblastoma could safely be discontinued at age four years.

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BackgroundThe travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed...

Retinoblastoma – Lessons Learned about Patterns of Care and Contributory Factors from 5 Years’ Experience in a Tertiary Care Center in Eastern India

Objectives: Retinoblastoma is the most common intraocular malignancy afflicting children worldwide. Even though there are enough data about the epidemiology of retinoblastoma in western population, there are only few reports from developing countries like India. In this retrospective study, we aimed to describe the epidemiological patterns, survival characteristics and prognostic factors of retinoblastoma.&#x0D; Materials and Methods: From medical records, we retrospectively analyzed the data of 68 children diagnosed in our hospital between January 2013 and December 2017 as having retinoblastoma. Data on sex, religion, laterality, age at diagnosis, presenting signs, family history, lag time for treatment, cause of such lag time and spread of tumor, treatment mode, and survival time were collected.&#x0D; Results: The median age of onset was 22 ± 19.73 months (range 2-92 months).The median patient age of onset of the unilateral cases was 23 ± 20.6 months, and that of the bilateral cases was 21 ±16.2 months. The median overall survival was 28.1±2.2 months. For unilateral cases, it was 30.1±2.5 months and for bilateral cases it was 19.7±2.9 months. The overall progression free survival (PFS) was 22.2±2.3 months. For unilateral cases, it was 24.18±2.7 months and for bilateral cases it was 13.9±2.9 months.&#x0D; 4 cases of familial retinoblastoma were reported. Among the 13 bilateral cases, 3 were found to have pinealoblastoma too. On Cox regression analysis, age of onset below 36 months, diagnostic delay of less than 5 months and delay of treatment initiation (after diagnosis) less than 2 months were found to have significant effect on OS. The former two were found to have significant effect on PFS but not the latter (p&lt;0.05 and HR&gt;1).&#x0D; Conclusions: Almost 81% of patients presented at an advanced stage of the disease, the reason being accounted by diagnostic and therapeutic delay by virtue of a number of causes, the major one being eluded by apparently nonviolent yet ineffective alternative medicine practices. In spite of following the institutional protocols which are at par to the international guidelines, analysis shows much poorer survival in this study compared to those of developed countries. The cause might be such late presentation of the cases in already advanced stages of the disease.

RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients (2,074 Eyes).

To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India. Retrospective study of 1,457 patients with RB (2,074 eyes). The mean age at presentation of RB was 29 months (median, 24 months; range, <1-370 months). There were 812 (56%) men and 645 (44%) women with unilateral presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment-included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively. The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.

Submillimeter retinoblastoma monitoring following transpupillary thermotherapy using hand-held optical coherence tomography

BackgroundPrecise, submillimeter visualization of retinal microstructures is useful for treatment monitoring of retinoblastoma. Herein, we report the use of hand-held optical coherence tomography (HH-OCT) to document a nearly-invisible retinoblastoma and monitor tumor response to transpupillary thermotherapy (TTT).Case presentationA 3-week-old boy was diagnosed with unilateral familial retinoblastoma in the left eye, classified as group B, and treated with intravenous chemoreduction. At 13-month follow-up, the tumor in the left eye was regressed, and evaluation of the right eye revealed a microscopic, nearly invisible tumor measuring 372 µm in thickness and 1.51 mm in basal dimension. The tumor was confirmed on HH-OCT and the diagnosis was changed to bilateral familial retinoblastoma. The new tumor was subsequently treated with TTT and after 1 month, the tumor regressed to an optically dense scar 166 µm in thickness by HH-OCT. Five months after TTT, the scar was clinically flat and measured 73 µm.ConclusionsHH-OCT has assumed a significant role in the monitoring of retinoblastoma in children. In this case, imaging with HH-OCT allowed precise localization of the tumor and submillimeter monitoring of treatment response following TTT.

Parafoveolar retinoblastoma regression with foveal preservation following intra-arterial chemotherapy documented on hand-held optical coherence tomography in a newborn

BackgroundOptical coherence tomography (OCT) has become an invaluable tool in retinoblastoma management, providing submillimeter visualization of tumor control following treatment. Herein, we document OCT-detection of a subtle tumor recurrence, allowing early intervention and achieving foveal microanatomy preservation.Case presentationA 3-week-old girl was diagnosed with bilateral familial retinoblastoma, classified as group D in the right eye (OD) and group B in the left eye (OS), and treated with intravenous chemoreduction. At 6-months follow-up, the right eye was under control, but the left eye revealed a subtle juxtafoveal tumor recurrence, documented on handheld OCT (HH-OCT) and measuring 2750 µm in diameter and 792 µm in thickness. Treatment with intraarterial chemotherapy (IAC) using 1 cycle of melphalan 5 mg was performed and complete tumor control was achieved, leaving a flat, concave scar 663 µm from the intact foveola and measuring 2750 µm in diameter and 120 µm in thickness. Foveal microanatomy OS was preserved on HH-OCT. The findings remained stable at 2 years following IAC.ConclusionsHH-OCT is an important tool in retinoblastoma management. In this case, HH-OCT allowed for early detection of retinoblastoma recurrence, before foveal invasion. Following treatment with IAC, complete tumor regression was noted and foveal microanatomy remained intact.

Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye

BackgroundChemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including...

Detection of Minimally Visible Recurrent Retinoblastoma by Hand-held Spectral-Domain Optical Coherence Tomography.

A 2-month-old male infant with bilateral familial retinoblastoma was treated with intravenous chemotherapy and focal adjuvant therapy. At 5 months of follow-up, fundus examination and ultrasonography disclosed no recurrence; however, hand-held spectral-domain optical coherence tomography (SD-OCT) demonstrated subclinical recurrence within a previous regression scar. Subsequent treatment led to flat scar. Hand-held SD-OCT can be a useful tool for detection of subclinical recurrent retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2017;54:e6-e8.].

Abstract IA02: The discovery of the hereditary colorectal cancer genes: A historical perspective

Abstract IA02: The discovery of the hereditary colorectal cancer genes: A historical perspective

Familial Retinoblastoma: Raised Awareness Improves Early Diagnosis and Outcome

Purpose. To study the impact of awareness of retinoblastoma in the affected families on the management and outcome of familial retinoblastoma patients. Methods and Materials. This is a retrospective, clinical case series of 44 patients with familial retinoblastoma. Collected data included patient's demographics, laterality, family history, age at diagnosis, presenting signs, treatment modalities, tumor stage, eye salvage rate, metastasis, and mortality. Results. Out of 200 retinoblastoma patients in our registry, 44 (22%) patients were familial, 18 were probands, and 26 were second, third, or fourth affected family members. There were 76 affected eyes: 31 eyes of probands and 45 eyes of the other affected family members. Among probands, all patients (100%) had at least one eye enucleated: 58% (18 eyes) of the affected eyes were enucleated and 32% (10 eyes) of the affected eyes were radiated. On the other hand, among the nonprobands, only 20% had one eye enucleated, and only 4 eyes (9%) received radiation. The eye salvage rate was significantly higher in the nonprobands than in the probands in this series (p = 0.00206). Patients diagnosed by screening (38%) had excellent visual outcome, and both eyes were salvaged. Conclusion. Awareness of families of the possibility of retinoblastoma and adequate screening led to a significantly higher rate of eye salvage in patients with familial retinoblastoma.