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Indian Journal of Ophthalmology Jun 2017Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to... (Review)
Review
Orbital extension is a major cause of death in children with retinoblastoma in the developing countries. Delayed detection and inappropriate management contribute to poor outcome. Conventional treatment including primary orbital exenteration or chemotherapy or radiotherapy alone result in mortality as high as 70%. The recent understanding on the role of sequential multimodal therapy with a combination of high-dose chemotherapy, followed by appropriate surgery, radiotherapy, and additional adjuvant chemotherapy has helped dramatically improve life salvage.
Topics: Combined Modality Therapy; Developing Countries; Humans; Morbidity; Retinal Neoplasms; Retinoblastoma; Survival Rate
PubMed: 28643706
DOI: 10.4103/ijo.IJO_352_15 -
Trends in Molecular Medicine Oct 2016Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology.... (Review)
Review
Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology. Retinoblastoma has also emerged as a model for translational research for pediatric solid tumors, which is particularly important as personalized medicine expands in oncology. Research on retinoblastomas has been combined with the exploration of retinal development and retinal degeneration to advance a new model of cell type-specific disease susceptibility termed 'cellular pliancy'. The concept can even be extended to species-specific regeneration. This review discusses the remarkable path of retinoblastoma research and how it has shaped the most current efforts in basic, translational, and clinical research in oncology and beyond.
Topics: Animals; Child; Humans; Precision Medicine; Regenerative Medicine; Retina; Retinal Neoplasms; Retinoblastoma; Translational Research, Biomedical
PubMed: 27567287
DOI: 10.1016/j.molmed.2016.07.010 -
Eye (London, England) Feb 2013Primary cancers of the eye are rare. These include uveal melanoma, a tumor that preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the... (Review)
Review
Primary cancers of the eye are rare. These include uveal melanoma, a tumor that preferentially affects the choroid of light-eyed, fair-skinned Europeans, and the pediatric retinal neoplasm retinoblastoma, which is slightly more common worldwide. Uveal melanoma kills about half of affected patients. Most succumb to hepatic metastases, which are unresponsive to current therapy. Factors indicative of poor prognosis include tumor size, ciliary body involvement, epithelioid cells, extraocular extension, lymphocytic and melanophagic infiltration, mitotic activity, vascular mimicry patterns, and most importantly, the detection of monosomy 3 and class 2 gene expression profile in tumor cells using special tests. Most retinoblastomas are caused by sporadic somatic mutations in the RB1 gene, but about one-third arise in infants with germline mutations. The latter tend to develop earlier, are often bilateral and are transmissible to offspring as an autosomal dominant trait. Retinoblastoma displays varying degrees of differentiation including Homer Wright and Flexner-Wintersteiner rosettes and photoreceptor differentiation (fleurettes). Rosettes are more common in eyes enucleated from very young infants. Tumors composed entirely of fleurettes (retinoma/retinocytoma) are thought to be retinoblastoma precursors, and like retinoblastoma, harbor mutations in both copies of the RB1 gene. Retinoblastoma is a major cancer treatment success story in developed countries where most deaths are caused by secondary tumors in germline mutation carriers. High-risk histopathological features that are an indication for adjuvant chemotherapy include massive uveal invasion and retrolaminar optic nerve invasion. Eye-sparing therapies including brachyradiotherapy and systemic and intra-arterial chemotherapy have reduced the number of eyes with retinoblastoma requiring enucleation in recent years.
Topics: Eye Neoplasms; Humans; Melanoma; Organ Sparing Treatments; Retinal Neoplasms; Retinoblastoma; Uveal Neoplasms
PubMed: 23154492
DOI: 10.1038/eye.2012.237 -
Oncogene Aug 2006The retinoblastoma gene Rb was the first tumor suppressor gene cloned, and it is well known as a negative regulator of the cell cycle through its ability to bind the... (Review)
Review
The retinoblastoma gene Rb was the first tumor suppressor gene cloned, and it is well known as a negative regulator of the cell cycle through its ability to bind the transcription factor E2F and repress transcription of genes required for S phase. Although over 100 other proteins have been reported to interact with Rb, in most cases these interactions are much less well characterized. Therefore, this review will primarily focus on Rb and E2F interactions. In addition to cell cycle regulation, studies of Rb and E2F proteins in animal models have revealed important roles for these proteins in apoptosis and differentiation. Recent screens of Rb/E2F target genes have identified new targets in all these areas. In addition, the mechanisms determining how different subsets of target genes are regulated under different conditions have only begun to be addressed and offer exciting possibilities for future research.
Topics: Animals; Apoptosis; Cell Differentiation; Eye Neoplasms; Gene Expression Regulation, Neoplastic; Genes, Retinoblastoma; Humans; Mammals; Multigene Family; Retinoblastoma
PubMed: 16936737
DOI: 10.1038/sj.onc.1209651 -
Eye (London, England) Apr 2023In this review we discuss several recent concepts regarding retinoblastoma control and its impact. In a cohort of 482 patients with solitary unilateral retinoblastoma... (Review)
Review
In this review we discuss several recent concepts regarding retinoblastoma control and its impact. In a cohort of 482 patients with solitary unilateral retinoblastoma revealed germline mutation in 16% and the likelihood of germline retinoblastoma was greater for younger children (≤1 year versus (vs.) >1 year at presentation) with odds ratio (OR) 2.96 (p = 0.001), and greatest for the youngest infants (≤3 months vs. >3-12 months) (OR 5.52) (p = 0.002). Retinocytoma/retinoma, a benign variant of retinoblastoma, was studied in 78 tumours and demonstrated transformation into retinoblastoma in 9.2% by 5 years and 15.3% by 10 years and 20 years. An international global study on retinoblastoma over 1.5 years revealed 4351 new patients and 85% from low- and middle-income countries, notably with older age at detection and greater risk for metastasis. Management of retinoblastoma in 964 eyes using intravenous chemotherapy showed 20-year globe salvage at 96% in group A, 90% in group B, 90% in group C, 68% in group D, and 32% in group E eyes. The 5-year globe salvage with intra-arterial chemotherapy for 160 eyes (655 infusions) with retinoblastoma showed success in 100% for group B, 80% for group C, 78% for group D, and 55% for group E. The psychological impact of retinoblastoma on the parents revealed depression (73%), anxiety (64%), and/or stress (100%), and on the patient revealed deficits in quality of life issues. Retinoblastoma is a challenging disease and chemotherapy provides reliable tumour control and globe salvage. Continuing efforts to improve quality of life issues is important.
Topics: Child; Infant; Humans; Retinoblastoma; Retinal Neoplasms; Global Burden of Disease; Quality of Life; Antineoplastic Combined Chemotherapy Protocols; Infusions, Intra-Arterial; Eye Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 35217824
DOI: 10.1038/s41433-022-01980-0 -
JAMA Ophthalmology Jan 2022High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma,...
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.
Topics: Eye Enucleation; Humans; Infant; Neoplasm Invasiveness; Optic Nerve Injuries; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Risk Factors; Surveys and Questionnaires
PubMed: 34762098
DOI: 10.1001/jamaophthalmol.2021.4732 -
Eye (London, England) Jan 2022To determine the association between the parental age gap and the absolute parental age with the risk of retinoblastoma (RB) development in an offspring.
OBJECTIVE
To determine the association between the parental age gap and the absolute parental age with the risk of retinoblastoma (RB) development in an offspring.
METHODS
RB individuals diagnosed between March 2013 and December 2019 in a single tertiary eye care centre were included. We recorded the demographic data, parental age and RB1 gene mutation status in the patient's tumour, blood and the parental blood. We categorised RB1 mutation inheritance as sporadic RB with somatic mutations (only present in tumour), heritable RB with de novo (present in patient's blood) and familial (present in patient and parents' blood) germline mutations. The statistical significance was confirmed by Fisher's exact/Chi-square test.
RESULTS
Out of 259 RB patients, 247 were included in our study. Heritable RB with de novo germline mutations was significantly less common (p value: 0.0387; 95% CI: 0.2676-0.9329) and sporadic RB with somatic mutations was more common (p value: 0.0545; 95% CI: 1.025-3.39), if the parental age gap was <10 years. There were increased odds of a heritable RB with de novo germline mutation with an increase in paternal age and this was more intensified when combined with parental age gap of more than ≥10 years. The heritable RB with de novo germline mutations significantly increased as maternal age progressed, only when it was adjusted to ≥10 years parental age gap (p value: 0.0262; 95% CI: 1.26-17.91).
CONCLUSIONS
An increased parental age gap and increased paternal age are independent risk factors for the development of heritable RB with de novo germline mutation.
Topics: Child; Demography; Humans; Mutation; Parents; Retinal Neoplasms; Retinoblastoma; Retrospective Studies
PubMed: 34799705
DOI: 10.1038/s41433-021-01771-z -
Indian Pediatrics Mar 2004
Topics: Child, Preschool; Corneal Opacity; Female; Humans; Pupil Disorders; Reflex, Abnormal; Reflex, Pupillary; Retinal Neoplasms; Retinoblastoma
PubMed: 15064521
DOI: No ID Found -
Cancer Causes & Control : CCC Sep 2012The etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California...
PURPOSE
The etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children.
METHODS
We identified 609 retinoblastoma cases (420 unilateral, 187 bilateral, and 2 with laterality unknown) from California Cancer Registry records of diagnoses 1988-2007 among children < 6 years of age. We randomly selected 209,051 controls from California birth rolls. The source of most study data was birth certificates. Multivariable logistic regression was used to examine associations between retinoblastoma and perinatal characteristics.
RESULTS
Bilateral retinoblastoma was associated with greater paternal age [for fathers over 35, crude odds ratio (OR) = 1.73, 95 % confidence interval (CI) 1.20, 2.47] and with twin births (OR = 1.93, 95 % CI 0.99, 3.79). Among unilateral cases, we observed an increased risk among children of US-born Hispanic mothers (OR = 1.34, 95 % CI 1.01, 1.77) while a decreased risk was observed for infants born to mothers with less than 9 years of education (OR = 0.70, 95 % CI 0.49, 1.00), a group that consisted primarily of mothers born in Mexico. We observed that maternal infection in pregnancy with any STD (OR = 3.59, 95 % CI 1.58, 8.15) was associated with bilateral retinoblastoma.
CONCLUSIONS
This study supports the findings of previous investigations reporting associations between parental age, HPV infection, and retinoblastoma.
Topics: Adult; California; Child; Educational Status; Female; Humans; Male; Mexican Americans; Odds Ratio; Paternal Age; Pregnancy; Prenatal Exposure Delayed Effects; Retinal Neoplasms; Retinoblastoma; Risk Factors; Socioeconomic Factors; Young Adult
PubMed: 22843021
DOI: 10.1007/s10552-012-0034-7 -
Indian Journal of Ophthalmology Feb 2023
Topics: Humans; Retinoblastoma; Developing Countries; Retinal Neoplasms; Melphalan
PubMed: 36727311
DOI: 10.4103/IJO.IJO_227_23