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Indian Journal of Ophthalmology Nov 2020Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation... (Review)
Review
Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cryotherapy; Eye Enucleation; Humans; Infant; Retinal Neoplasms; Retinoblastoma
PubMed: 33120616
DOI: 10.4103/ijo.IJO_721_20 -
Indian Journal of Pediatrics Dec 2017Retinoblastoma represents 3% of all childhood cancers, and is the most common intraocular malignancy of childhood. It is fatal, if untreated. White eye reflex, also... (Review)
Review
Retinoblastoma represents 3% of all childhood cancers, and is the most common intraocular malignancy of childhood. It is fatal, if untreated. White eye reflex, also known as leukocoria, is the commonest sign, followed by strabismus. The pediatricians have a very important role to play in the diagnosis of this relatively rare, but easily detectable tumor. Early diagnosis yields better results. The management of retinoblastoma has gradually evolved over the past few decades, with an aim to not only preserve life and eye, but also optimize residual vision. The treatment of retinoblastoma is multimodal, with chemotherapy, focal treatment including trans-pupillary thermotherapy, cryotherapy and laser photocoagulation, radiation therapy and surgery, all playing a vital role. Intravenous chemotherapy has been the mainstay of treatment for the past two decades, and still continues to be the most extensively used eye-saving modality of treatment. Periocular and intravitreal chemotherapy have specific indications in the management of retinoblastoma. Intra-arterial chemotherapy has emerged as a promising alternative for advanced and refractory retinoblastoma, both as a primary and secondary therapy. Recent advances in genetics of retinoblastoma have also helped in improving the overall clinical management of this malignancy.
Topics: Combined Modality Therapy; Diagnosis, Differential; Early Detection of Cancer; Humans; Infant, Newborn; Neoplasm Staging; Retinal Neoplasms; Retinoblastoma
PubMed: 28620731
DOI: 10.1007/s12098-017-2395-0 -
The New England Journal of Medicine Jun 2022
Topics: Eye Neoplasms; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 35731655
DOI: 10.1056/NEJMicm2118356 -
Nature Communications Jul 2021Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a...
Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation.
Topics: Adult; Cell Differentiation; Cell Line; Epigenesis, Genetic; Exons; Female; Genome, Human; Germ-Line Mutation; Humans; Imaging, Three-Dimensional; Induced Pluripotent Stem Cells; Organoids; Retina; Retinoblastoma; Retinoblastoma Protein; Stem Cells
PubMed: 34315877
DOI: 10.1038/s41467-021-24781-7 -
Journal of Child Neurology Feb 2016Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the... (Review)
Review
Retinoblastoma is the most common primary intraocular malignancy of childhood. It typically presents with leukocoria or strabismus. In later stages of the disease, the child may exhibit proptosis, buphthalmos, or hypopyon. The pathognomonic molecular aberration is a loss of function mutation in the RB1 gene on chromosome 13q. The degree of tumor involvement within the eye is defined by its group. Grouping was historically done with Reese-Ellsworth System. Recent therapeutic advances have led to the development of a new grouping system, the International Classification of Retinoblastoma (ICRB). In cases of extraocular extension and metastatic disease, the degree of tumor involvement outside of the eye is defined by its stage. Retinoblastoma is staged using the International Retinoblastoma Staging System (IRSS). Children with intraocular retinoblastoma have an excellent overall and ocular survival. In order to avoid the morbidity of enucleation and external beam radiation, treatments for isolated intraocular retinoblastoma have progressively moved toward targeted local modalities. Patients with extraocular involvement, such as those with trilateral retinoblastoma, have a poorer prognosis. The majority of these higher stage patients are now able to be cured with combination chemotherapy.
Topics: Child; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 26023180
DOI: 10.1177/0883073815587943 -
Current Opinion in Ophthalmology Nov 2013Retinoblastoma is the most common malignant intraocular tumor of childhood. Treatment and diagnostic modalities associated to this condition are changing rapidly as our... (Review)
Review
PURPOSE OF REVIEW
Retinoblastoma is the most common malignant intraocular tumor of childhood. Treatment and diagnostic modalities associated to this condition are changing rapidly as our understanding of this condition crystallizes. The purpose of this review is to provide an update of the current understanding of retinoblastoma.
RECENT FINDINGS
Knowledge on tumorigenesis and genomic expression has expanded tremendously with the development of a mouse model for retinoblastoma. Tumor hypoxia has been identified as a significant step in the tumor progression and a novel target for future treatments. Current globe-sparing therapies, including periocular carboplatin, selective ophthalmic artery chemoreduction, intravitreal melphalan, and focal consolidation are being used and investigated actively. Diagnosis and the management of retinoblastoma is also undergoing major advances including wide-field photography, autofluorescence, and high-resolution optical coherence tomography.
SUMMARY
Progressive advances in the understanding of retinoblastoma pathogenesis continue to lead treatment strategies. Improvements in the diagnosis and management of retinoblastoma are improving morbidity and mortality associated to this condition in the developed nations. However, it is of outmost importance to flatten the international boundaries to offer prompt care to retinoblastoma children in underdeveloped communities.
Topics: Child, Preschool; Humans; Infant; Retinal Neoplasms; Retinoblastoma
PubMed: 24100372
DOI: 10.1097/ICU.0000000000000002 -
Singapore Medical Journal Feb 2012Retinoblastoma is the most common intraocular malignancy in children and one of the very few life-threatening ophthalmic conditions. Genetically, the disease may be... (Review)
Review
Retinoblastoma is the most common intraocular malignancy in children and one of the very few life-threatening ophthalmic conditions. Genetically, the disease may be heritable or non-heritable. It can have unilateral or bilateral involvement and can present either sporadically or with a positive family history. Leukocoria and strabismus are the most common presentations. Diagnosis is made by indirect ophthalmoscopy aided by imaging techniques. Multidisciplinary management is aimed at saving lives, salvaging the globe and maintaining good vision. The use of neoadjuvant chemotherapy and focal treatments, such as cryotherapy, laser photocoagulation, transpupillary thermotherapy, brachytherapy and periocular chemotherapy, form the mainstay of globe preserving treatment in retinoblastoma. In developing countries, retinoblastoma is unfortunately accompanied by a high mortality rate due to delayed diagnosis made at advanced stages of the disease. Early diagnosis and timely management are vital for a good prognosis.
Topics: Child; Humans; Retina; Retinal Neoplasms; Retinoblastoma
PubMed: 22337189
DOI: No ID Found -
Orphanet Journal of Rare Diseases Aug 2006Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of... (Review)
Review
Retinoblastoma is a rare eye tumor of childhood that arises in the retina. It is the most common intraocular malignancy of infancy and childhood; with an incidence of 1/15,000-20,000 live births. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Iris rubeosis, hypopyon, hyphema, buphthalmia, orbital cellulites and exophthalmia may also be observed. Sixty per cent of retinoblastomas are unilateral and most of these forms are not hereditary (median age at diagnosis two years). Retinoblastoma is bilateral in 40% of cases (median age at diagnosis one year). All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma constitutes a cancer predisposition syndrome: a subject constitutionally carrying an RB1 gene mutation has a greater than 90% risk of developing retinoblastoma but is also at increased risk of developing other types of cancers. Diagnosis is made by fundoscopy. Ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may contribute to diagnosis. Management of patients with retinoblastoma must take into account the various aspects of the disease: the visual risk, the possibly hereditary nature of the disease, the life-threatening risk. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. Conservative treatment for at least one eye is possible in most of the bilateral cases. It includes laser alone or combined with chemotherapy, cryotherapy and brachytherapy. The indication for external beam radiotherapy should be restricted to large ocular tumors and diffuse vitreous seeding because of the risk of late effects, including secondary sarcoma. Vital prognosis, related to retinoblastoma alone, is now excellent in patients with unilateral or bilateral forms of retinoblastoma. Long term follow-up and early counseling regarding the risk of second primary tumors and transmission should be offered to retinoblastoma patients.
Topics: Child, Preschool; Diagnosis, Differential; Eye Diseases; Female; Humans; Infant; Pregnancy; Prenatal Diagnosis; Prognosis; Rare Diseases; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Protein
PubMed: 16934146
DOI: 10.1186/1750-1172-1-31 -
Pediatric Annals Jan 1979Retinoblastoma is a radiosensitive malignancy of neuroblastic origin that primarily affects young children. Its relatively low incidence belies its potential importance... (Review)
Review
Retinoblastoma is a radiosensitive malignancy of neuroblastic origin that primarily affects young children. Its relatively low incidence belies its potential importance in the understanding of tumor biology in general. A case is made for referral of all retinoblastoma patients to centers with retinoblastoma protocols.
Topics: Child; Eye Neoplasms; Humans; Mutation; Neoplasm Regression, Spontaneous; Neoplasms, Multiple Primary; Retinoblastoma
PubMed: 372907
DOI: 10.3928/0090-4481-19790101-05 -
Proceedings of the National Academy of... Apr 1971Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events....
Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.
Topics: Child, Preschool; Eye Neoplasms; Female; Functional Laterality; Humans; Infant; Male; Mutation; Retinoblastoma; Retrospective Studies; Statistics as Topic
PubMed: 5279523
DOI: 10.1073/pnas.68.4.820