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Journal of Pediatric Ophthalmology and... 2021To report the presenting signs of retinoblastoma in a large cohort of patients who underwent orthoptic assessment at presentation.
PURPOSE
To report the presenting signs of retinoblastoma in a large cohort of patients who underwent orthoptic assessment at presentation.
METHODS
A retrospective medical chart review was conducted on 131 patients with retinoblastoma who presented consecutively to a single institution during a 6-year period. The main outcome measure was the presenting sign(s) of the disease.
RESULTS
Of 131 patients with retinoblastoma, 88 presented with unilateral disease and 43 presented with bilateral disease (mean ages: 22.7 and 14.8 months, respectively). Leukocoria was the presenting sign in 56% of patients, leukocoria and strabismus in 18%, strabismus in 13%, inflammation in 8%, and "other" signs in 5%. The fovea was affected by the retinoblastoma tumor or its sequelae in 75% of patients. Patients who presented with strabismus were significantly more likely to have foveal involvement than patients who presented with leukocoria alone ( = .001). Thirty-one percent of patients had strabismus as a component of their presentation; 63% had exotropia, 23% had esotropia, and 14% had variable strabismus. The percentage of patients with strabismus increased to 66% when small angle and variable strabismus were also considered. Patients with inflammation had worse ocular survival ( < .05).
CONCLUSIONS
This study assessed the combination of leukocoria and strabismus as presenting features of retinoblastoma. Foveal involvement is common in patients who have strabismus and may influence decision-making regarding globe salvage. The authors confirmed that exotropia is more common than esotropia in retinoblastoma in the largest cohort to have undergone an orthoptic assessment. .
Topics: Humans; Infant; Pupil Disorders; Retinal Neoplasms; Retinoblastoma; Retrospective Studies; Strabismus
PubMed: 34592118
DOI: 10.3928/01913913-20210614-03 -
Neuro-Signals Nov 2022Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then... (Review)
Review
Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then preservation of the globe and useful vision. With modern treatment protocols and early disease detection success rates can reach up to 100% of disease-free-globe and eye preservation. Treatment of advanced cases remains complex, requiring aggressive chemotherapy or/and external beam radiation. Treatment protocols are extremely diverse and dependent on local resources thus success rates are variable. Here we review narratively current treatment protocols and failure rates based on a PubMed search using keywords of retinoblastoma, retinoblastoma seed, retinoblastoma treatment, enucleation.
Topics: Humans; Infant; Retinoblastoma; Retinal Neoplasms; Eye Enucleation; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36354963
DOI: 10.33594/000000585 -
Asia-Pacific Journal of Ophthalmology... 2024Retinoblastoma stands as a paradigm of success in treating malignancies among pediatric patients. Over recent decades, the approach to managing retinoblastoma has... (Review)
Review
Retinoblastoma stands as a paradigm of success in treating malignancies among pediatric patients. Over recent decades, the approach to managing retinoblastoma has evolved significantly, transitioning from the preservation of patients' lives to the preservation of eyes and vision while minimizing treatment-related complications. Chemotherapy, administered through diverse routes, has solidified its role as the cornerstone of retinoblastoma treatment. In addition to intravenous chemotherapy (IVC), alternative administration routes, including intraarterial (IAC), intravitreal, intracameral, and periocular delivery, have emerged as promising modalities for retinoblastoma management. Numerous studies have demonstrated outstanding outcomes, achieving nearly 100% salvage rates for eyes classified under groups A-C. However, for advanced intraocular retinoblastoma (groups D and E eyes), IAC appears to offer superior local control rates compared to IVC. Intravitreal injection of chemotherapeutic agents, when administered in a controlled and secure manner, holds promise in averting the need for enucleation and radiotherapy in advanced retinoblastoma cases presenting with vitreous seeds. The optimal chemotherapy strategy remains meticulously tailored based on numerous factors. This review provides a comprehensive update on chemotherapy across various routes, encompassing key considerations, dosages, administration methods, treatment outcomes, and potential complications. Furthermore, it explores emerging potential treatments and outlines future directions aimed at enhancing treatment outcomes.
Topics: Retinoblastoma; Humans; Retinal Neoplasms; Antineoplastic Agents; Intravitreal Injections
PubMed: 38641204
DOI: 10.1016/j.apjo.2024.100061 -
Molecular Biology of the Cell Dec 2021Few ideas in cancer genetics have been as influential as the "two-hit" theory of tumor suppressors. This idea was introduced in 1971 by Al Knudson in a paper in the...
Few ideas in cancer genetics have been as influential as the "two-hit" theory of tumor suppressors. This idea was introduced in 1971 by Al Knudson in a paper in the Proceedings of the National Academy of Science and forms the basis for our current understanding of the role of mutations in cancer. In this theoretical discussion proposing a genetic basis for retinoblastoma, a childhood cancer of the retina, Knudson posited that these tumors arise from two inactivating mutations, targeting both alleles of a putative tumor suppressor gene. While this work built on earlier proposals that cancers are the result of mutations in more than one gene, it was the first to propose a plausible mechanism by which single genes that are affected by germ-line mutations in heritable cancers could also cause spontaneous, nonheritable tumors when mutated in somatic tissues. Remarkably, Knudson described the existence and properties of a retinoblastoma tumor suppressor gene a full 15 years before the gene was cloned.
Topics: Animals; Genes, Tumor Suppressor; Haploinsufficiency; Humans; Mice; Mutation; Neoplasms; Retinal Neoplasms; Retinoblastoma
PubMed: 34735271
DOI: 10.1091/mbc.E21-08-0407 -
Pediatric Blood & Cancer Nov 2020While there is evidence that parental exposure to medical radiation is associated with increased risk of sporadic bilateral retinoblastoma in offspring, this association...
BACKGROUND
While there is evidence that parental exposure to medical radiation is associated with increased risk of sporadic bilateral retinoblastoma in offspring, this association has not been confirmed. Additionally, the relationship between paternal and maternal exposures and sporadic unilateral retinoblastoma has not been fully investigated.
PROCEDURE
Data were obtained from two large multicenter case-control studies of retinoblastoma. For the paternal analyses, 268 bilateral cases, 155 unilateral cases, and 358 controls were included. For the maternal analyses, 298 bilateral cases, 184 unilateral cases, and 404 controls were included. Logistical regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) to evaluate the associations between parental exposures to medical radiation and sporadic retinoblastoma, while adjusting for potential confounders.
RESULTS
Paternal exposure to medical radiation was not significantly associated with sporadic bilateral retinoblastoma in offspring. However, increasing paternal exposure to gonadal radiation was associated with increased risk of unilateral retinoblastoma (P-trend = .03). Maternal history of upper and lower gastrointestinal (GI) series was associated with bilateral retinoblastoma (OR = 1.9, 95% CI: 1.1-3.2 and OR = 6.9, 95% CI: 2.9-16.4, respectively). However, there was no association between maternal exposure to medical radiation and unilateral retinoblastoma in offspring.
CONCLUSION
Our investigation adds to the evidence that medical radiation exposure in fathers as well as mothers prior to pregnancy may increase the risk of germline alterations leading to the development of retinoblastoma in their offspring. However, our findings could point to a more complex etiological framework for this important pediatric malignancy.
Topics: Adult; Case-Control Studies; Child; Female; Follow-Up Studies; Humans; Male; Maternal Exposure; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Prognosis; Radiation Exposure; Retinal Neoplasms; Retinoblastoma; Risk Factors
PubMed: 32743912
DOI: 10.1002/pbc.28633 -
Healthcare Quarterly (Toronto, Ont.) Apr 2022Peer-to-peer recruitment efforts are important in generating interest and participation of patients as partners in research but difficult to sustain when face-to-face...
Peer-to-peer recruitment efforts are important in generating interest and participation of patients as partners in research but difficult to sustain when face-to-face interactions are limited. The Retinoblastoma Research and You! booklet, co-developed by patients, researchers and health professionals, serves as a guide for patient engagement in research while retaining an element of personalization. The Retinoblastoma Research and You! booklet was developed through two virtual workshops to iterate and finalize the booklet design and content. The booklet outlines how individual patients' lived experiences and skills can influence retinoblastoma research and highlights real-world examples of patient-partnered research activities at different stages of the research process.
Topics: Health Personnel; Humans; Pamphlets; Patient Participation; Retinal Neoplasms; Retinoblastoma
PubMed: 35467513
DOI: 10.12927/hcq.2022.26772 -
Ophthalmic Genetics Oct 2021: Retinoblastoma is the most common intraocular cancer in children in which above 90% of bilateral cases and 10-25% of unilateral cases have germline mutations. We...
: Retinoblastoma is the most common intraocular cancer in children in which above 90% of bilateral cases and 10-25% of unilateral cases have germline mutations. We summarized the spectrum of germline mutations and the clinical manifestations of unilateral retinoblastomas to guide clinical treatments.: Two hundred and sixty-three unrelated patients with unilateral retinoblastoma and their parents were included between February 2014 and August 2020. Next-generation sequencing and Sanger sequencing analysis of the core promoter region and exons 1-27 including flanking intronic regions of the gene were performed. If a germline mutation was identified in a retinoblastoma patient, the parental blood sample was requested to test for the identified mutation.: germline mutations were identified in 39/263 (14.8%) unilateral retinoblastoma patients and 11 (28.2%) had a missense mutation, 10 (25.6%) had nonsense mutations, 2 (5.1%) had frameshifts, 1 (2.6%) had synonymous mutation, and 7 (17.9%) had a large deletion, 2 (5.1%) had splice site mutations, 6 (15.4%) had variant of uncertain significance. Moreover, 27 (69.2%) of 39 patients identified mutations were predicted to have pathogenic mutation. The median age at diagnosis of patients with identified pathogenic mutations was 16.9 months and the patients with the wild-type allele was 21.1 months ( = .323). The rate of germline mutations is 14.8% in our cohort of unilateral retinoblastomas. The high incidence of germline mutations indicates that genetic testing and counseling for families of unilateral retinoblastoma patients would be beneficial.
Topics: Asian People; Child; Child, Preschool; China; DNA Mutational Analysis; Exons; Female; Genes, Retinoblastoma; Genetic Testing; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Introns; Male; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Binding Proteins; Ubiquitin-Protein Ligases
PubMed: 34190019
DOI: 10.1080/13816810.2021.1946703 -
Pediatric Blood & Cancer Feb 2023Retinoblastoma is the most common intraocular childhood cancer and is typically diagnosed in young children. With increasing number of survivors and improved medical...
BACKGROUND
Retinoblastoma is the most common intraocular childhood cancer and is typically diagnosed in young children. With increasing number of survivors and improved medical outcomes, long-term psychosocial impacts need to be explored. Thus, the current study sought to assess functioning in school-aged survivors of retinoblastoma.
PROCEDURE
Sixty-nine survivors of retinoblastoma underwent a one-time evaluation of psychosocial functioning. Survivors (M = 10.89 years, SD = 1.07 years; 49.3% male; 56.5% unilateral disease) and parents completed measures of quality of life (QoL; PedsQL) and emotional, behavioral, and social functioning (PROMIS [patient-reported outcome measurement information system] Pediatric Profile, BASC-2 parent report). Demographic and medical variables were also obtained.
RESULTS
On the whole, both survivors and caregivers indicated QoL and behavioral and emotional health within the typical range of functioning. Survivors reported better physical QoL compared to both parent report and a national healthy comparison sample, whereas caregivers reported that survivors experienced lower social, school, and physical QoL than a healthy comparison. Regarding behavioral and emotional health, survivors indicated more anxiety than a nationally representative sample. Parents of female survivors endorsed lower adaptive scores than parents of male survivors.
CONCLUSIONS
Results indicated that survivors of retinoblastoma reported QoL and behavioral and emotional health within normal limits, although parents appear to perceive greater impairment across several assessed domains. Understanding both survivor and parent reports remains important for this population. Future research should explore psychosocial functioning of these survivors as they transition to adolescence and early adulthood, given the increased independence and behavioral and emotional concerns during these developmental periods.
Topics: Adolescent; Humans; Male; Child; Female; Child, Preschool; Adult; Retinoblastoma; Quality of Life; Survivors; Health Status; Retinal Neoplasms; Surveys and Questionnaires
PubMed: 36385462
DOI: 10.1002/pbc.29983 -
Advances in Biological Regulation May 2023Small cell lung cancer (SCLC) often exhibits Rb deficiency, TRβ and p130 deletion, and SKP2 amplification, suggesting TRβ inactivation and SKP2 activation. It is... (Review)
Review
Targeted pharmacologic inhibition of S-phase kinase-associated protein 2 (SKP2) mediated cell cycle regulation in lung and other RB-Related cancers: A brief review of current status and future prospects.
Small cell lung cancer (SCLC) often exhibits Rb deficiency, TRβ and p130 deletion, and SKP2 amplification, suggesting TRβ inactivation and SKP2 activation. It is reported that SKP2 targeted therapy is effective in some cancers in vitro and in vivo, but it is not reported for the treatment of SCLC and retinoblastoma. SKP2 is the synthetic lethal gene in SCLC and retinoblastoma, so SKP2 can be used for targeted therapy in SCLC and retinoblastoma. RB1 knockout mice develop several kinds of tumors, but Rb1 and SKP2 double knockout mice are healthy, suggesting that SKP2 targeted therapy may have significant effects on Rb deficient cancers with less side effects, and if successful in SCLC and retinoblastoma in vitro and in animal model, such compounds may be promising for the clinical treatment of SCLC, retinoblastoma, and variety of Rb deficient cancers. Previously our studies showed that retinoblastomas exhibit retinal cone precursor properties and depend on cone-specific thyroid hormone receptor β2 (TRβ2) and SKP2 signaling. In this study, we sought to suppress SCLC and retinoblastoma cell growth by SKP2 inhibitors as a prelude to targeted therapy in vitro and in vivo. We knocked down TRβ2 and SKP2 or over-expressed p27 in SCLC and retinoblastoma cell lines to investigate SKP2 and p27 signaling alterations. The SCLC cell lines H209 as well as retinoblastoma cell lines Y79, WERI, and RB177 were treated with SKP2 inhibitor C1 at different concentrations, following which Western blotting, Immunostaining, and cell cycle kinetics studies were performed to study SKP2 and p27 expression ubiquitination, to determine impact on cell cycle regulation and growth inhibition. TRβ2 knockdown in Y79, RB177 and H209 caused SKP2 downregulation and degradation, p27 up-regulation, and S phase arrest, whereas, SKP2 knockdown or p27 over-expression caused p27 accumulation and G1-S phase arrest. In the cell lines Y79, WERI, RB177, and H209 treatment with C1 caused SKP2 ubiquitination and degradation, p27 de-ubiquitination and accumulation, and cell growth arrest. SKP2 inhibitor C1 significantly suppressed retinoblastoma as well as SCLC cell growth by SKP2 degradation and p27 accumulation. In vivo study also showed inhibition of tumor growth with C1 treatment. Potential limitations of the success of such a therapeutic approach and its translational application in human primary tumors, and alternative approaches to overcome such limitations are briefly discussed for the treatment of retinoblastoma, SCLC and other RB-related cancers.
Topics: Mice; Animals; Humans; Retinoblastoma; S-Phase Kinase-Associated Proteins; Retinoblastoma Protein; Cell Line, Tumor; Cell Cycle; Mice, Knockout; Retinal Neoplasms; Lung
PubMed: 37004354
DOI: 10.1016/j.jbior.2023.100964 -
Journal of Pediatric Ophthalmology and... 2021
Topics: Eye Neoplasms; Humans; Infant; Retinal Neoplasms; Retinoblastoma
PubMed: 34851786
DOI: 10.3928/01913913-20211012-01