What is the prognosis of retinoblastoma in a two-year-old?

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Elsevier ClinicalKey Clinical Overview

Complications and Prognosis Patients with mosaic alleles have fewer tumors, and tumors are more likely to remain unilateral Orbital and locoregional extension cure rate is 60% to 85% Factors associated with poorer prognosis include: Tumor larger than 3 mm and in close proximity (within 1.5 mm) to the center of the fovea or the margin of the optic disk; associated with worse ocular survival than smaller localized tumors or tumors further from critical ocular structures Tumor at the margin of the transected optic nerve; associated with a very high mortality rate (up to 80%) Extension to the lamina cribrosa; carries a 29% mortality rate, while tumor extension posterior to the lamina cribrosa carries a 42% mortality rate Central nervous system disease; prognosis is dismal despite treatment Extracranial hematogenous metastatic disease; universally fatal despite treatment Subretinal or vitreous seeding; carries a high risk of recurrence

Complications and Prognosis Visual prognosis Group A: almost all eyes are preserved with excellent visual acuity with focal modalities alone Group B: prognosis is good (90%-95%) for eye salvage with combination of systemic chemotherapy and focal treatment; visual outcomes vary from 20/20 to 20/200 depending on vital ocular structure involvement Group C: ocular salvage rate is about 70% to 80% with chemoreduction Group D: (eyes with diffuse dissemination and more advanced disease): ocular salvage rate is less than 50% with use of advanced treatment modalities (eg, external-beam radiation, intravitreal melphalan) Group E: enucleation is usually recommended; poor salvage rate with chemoreduction Overall cure rate for retinoblastoma is greater than 95% with small localized tumors and prompt medical care Bilateral disease is associated with a survival rate at 15 years of approximately 86% Mortality due to metastatic retinoblastoma increases with increasing size of primary tumor; highest risk for metastasis when tumor comprises two-thirds or more of the globe volume or is diffuse infiltrating retinoblastoma More deaths occur in patients with heritable (germline) retinoblastoma from a second primary malignancy than from initial retinoblastoma 5 years after initial diagnosis Patients who are heterozygous for regular-penetrance RB1 variants may have greater risk of subsequent malignancies than patients with incomplete-penetrance variants Patients with mosaic alleles have fewer tumors, and tumors are more likely to remain unilateral Orbital and locoregional extension cure rate is 60% to 85% Factors associated with poorer prognosis include:

Approximately 95% of U.S. children with retinoblastoma are cured with modern treatment. Current efforts using chemotherapy in combination with focal therapy are intended to preserve useful vision and avoid external-beam radiation or enucleation. Unfortunately, the diagnosis of retinoblastoma in many children from resource-poor countries is delayed, resulting in spread of the tumor outside the orbit. The prognosis for children with retinoblastoma that has spread outside the eye is poor. Trilateral retinoblastoma, disease involving both eyes and the pineal region, is almost universally fatal. Children with germlineRB1pathologic genetic variants are at significant risk for development ofsecond malignancies, especially osteosarcoma, as well as soft tissue sarcomas and malignant melanoma. The risk of second malignancies is further increased by the use of radiation therapy. Other radiation-related late adverse effects include cataracts, orbital growth deformities, lacrimal dysfunction, and late retinal vascular injury. Visit Elsevier eBooks+ ateBooks.Health.Elsevier.comfor Bibliography.

Synopsis Most children with extraocular involvement are cured with a more intensive combination of treatment modalities, but overall prognosis is poor; enucleation is usually necessary given more extensive disease at diagnosis Complications include disease-associated events such as loss of affected eye(s) or loss of vision, as well as treatment-associated conditions including secondary malignancies, recurrence, retinal detachment, and cataracts Hereditary retinoblastoma imparts a predisposition to malignancy; one-half of the patients carrying this autosomal dominant defect will develop a second malignancy by age 50 years Offer genetic counseling to all children with a family history of retinoblastoma and all parents of a child with retinoblastoma Patients with retinoblastoma isolated to the orbit have an excellent ocular survival rate with an overall cure rate greater than 95%

Treatment Trilateral retinoblastoma Bilateral retinoblastoma associated with a concomitant primitive neuroectodermal tumor, usually located in the midline pineal gland or suprasellar location Occurs in less than 10% of bilateral cases Discrete malignancy; does not represent a metastasis from the eye tumor May be diagnosed at the same time as eye tumor by reviewing MRI of the brain, before eye tumor develops, or a number of years after diagnosis of eye tumor Typically, more than 20 months elapse between diagnosis of bilateral retinoblastoma and diagnosis of brain tumor Prognosis is poor and accounts for the majority of early retinoblastoma deaths; the mean length of survival after diagnosis is 9.7 to 11.2 months if treated 5-year event-free survival rate is 53% with tumor response to systemic chemotherapy and aggressive treatment (including stem cell transplant) Patients with germline RB1 mutation carry a 5% to 10% chance of developing trilateral retinoblastoma Quadrilateral retinoblastoma Rarely, bilateral retinoblastoma associated with both pineal region and suprasellar intracranial primary primitive neuroectodermal tumors Prognosis is very poor

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Olitsky, Scott E., Marsh, Justin D. (2025). In Nelson Textbook of Pediatrics (pp. 3955). DOI: 10.1016/B978-0-323-88305-4.00670-2

Therapy varies, depending on the size and location of the tumor as well as whether it is unilateral or bilateral. Advanced tumors may be treated by enucleation. Other treatment modalities include the use of external beam irradiation, radiation plaque therapy, laser or cryotherapy, and chemoreduction (systemic chemotherapy) followed by local therapies (i.e., laser therapy, cryotherapy, and brachytherapy). During the last decade, there has been a dramatic shift in the treatment of retinoblastomas. Intraarterial chemotherapy involves delivery of chemotherapeutic agents via the ophthalmic artery and has dramatically reduced the need for enucleation in many cases of retinoblastoma. Nonocular secondary tumors are common in patients with germinal pathogenic variants; they are estimated to occur with an incidence of 1% per years of life. The most common secondary tumor is osteogenic sarcoma of the skull and long bones; the risk is higher in patientstreated with radiation. Other malignancies include lung, brain, soft tissue, and skin. The prognosis for children with retinoblastoma depends on the size and extension of the tumor. When confined to the eye, most tumors can be cured. The prognosis for long-term survival is poor when the tumor has extended into the orbit or along the optic nerve.