Newly Diagnosed With Retinoblastoma

Retinoblastoma is a cancer of the retina. The retina is the light-sensing layer at the back of the eye. This is a disease of very young children. Two-thirds of cases are found before age 2. It makes up about 3 percent of cancers in children under 15.

The numbers are small. In the United States the estimated annual incidence is about 3 cases per million children under 20. Narrowed to ages 0 to 4, it is 18.4 cases per million. That rarity is why care belongs at a center that sees these tumors regularly.

The most common first sign is leukocoria. That means a white reflection in the pupil instead of the usual red. It is often first spotted in a flash photograph. A squint, also called strabismus, is the other common first sign.

About 25 to 30 percent of retinoblastoma is heritable and 70 to 75 percent is not. The distinction changes almost everything that follows.

Retinoblastoma is driven by loss of both working copies of the RB1 gene. In heritable disease, the child was born with one faulty copy in every cell. It then takes only one more event in one retinal cell to start a tumor. That is why heritable cases show up earlier, in both eyes, and with more than one tumor.

One point surprises many families. Children with disease in both eyes almost all have the heritable form. Yet only about 25 percent have a parent who had it. Most heritable cases are new mutations. A clean family history does not rule this out.

Testing for RB1 in the child, and then in relatives, is standard. NCI publishes a table of risk to relatives. Take a person who had disease in both eyes. Their child has a 50 percent pretest risk of carrying the mutant gene copy. A sibling of that person has a 2.5 percent risk. General population risk works out to roughly 1 in 15,000 live births.

Ask for a genetic counselor referral in the first weeks, not later. It determines whether siblings need eye exams under anesthesia.

Retinoblastoma inside the eye is usually diagnosed without a biopsy. Taking tissue risks spreading tumor cells. Instead the child has an exam under anesthesia. The pupil is fully dilated and the eye wall is pressed in to see the far edges. Imaging supports it. That is what sets the diagnosis and the group.

The International Classification of Retinoblastoma sorts each eye from A to E:

• Group A: small tumors, all 3 mm or smaller, confined to the retina, more than 3 mm from the fovea and 1.5 mm from the optic disc.
• Group B: other discrete tumors confined to the retina, including those closer to the optic nerve or fovea, with subretinal fluid less than 3 mm from the tumor and no seeding.
• Group C: discrete tumors with minimal seeding. Subretinal fluid involving up to a quarter of the retina, local fine vitreous seeding near the tumor, and subretinal seeding under 3 mm from it.
• Group D: diffuse disease with significant vitreous or subretinal seeding, possibly with total retinal detachment.
• Group E: the most advanced category.

Each eye gets its own group. A child can be group B in one eye and group D in the other, with different treatment for each.

Systemic chemotherapy shrinks tumors first. It is often called chemoreduction. A common combination is vincristine, carboplatin, and etoposide, over six cycles. Local treatment such as laser or freezing then finishes the tumors off.

Intra-arterial chemotherapy is also called ophthalmic artery chemosurgery. A thin catheter is threaded up to the artery feeding the eye. The drug goes in there. Melphalan is the main agent, sometimes with topotecan or carboplatin. Used first, it saves the eye at high rates. Used after other treatment has failed, the rates are consistently lower.

Enucleation means removing the eye. It is still the right answer for advanced disease in one eye, especially when the other eye is healthy. It is not a failure of care. In one large series, 30 percent of removed eyes showed high-risk features on pathology. Those findings then guided extra chemotherapy.

Ask which treatments are being offered for each eye separately, and what the estimated chance of saving each eye is.

Trilateral retinoblastoma. In 5 to 15 percent of children with heritable disease, a separate tumor grows in the midline of the brain. It usually appears between 20 and 36 months of age. Before routine brain scans and chemoreduction, this caused more than half of retinoblastoma deaths in the first decade after diagnosis. Routine brain imaging can find most cases within 2 years of the first diagnosis. Ask what the imaging schedule is.

Second cancers. Children with heritable retinoblastoma carry a lifelong raised risk of new, separate cancers. The most common is osteosarcoma, a bone cancer. Next come soft tissue sarcoma and melanoma. This extra risk lasts into later decades and applies to those with disease in both eyes. It shapes choices about radiation, which raises the risk further. It also means follow-up does not end in childhood.

• Ask for the group letter for each eye, written down.
• Ask when the RB1 genetic test was sent and when results are due.
• Ask whether siblings and parents need eye examinations, and who books them.
• Ask which center will do the treatment, and how many retinoblastoma cases they treat a year.
• Ask what vision is realistically expected in each eye under the proposed plan.
• Ask what the imaging schedule is for the brain and how long it continues.

• Call 911 or go to an emergency department if your child has a seizure, becomes hard to rouse, or cannot be settled and is vomiting hard, especially first thing in the morning. Those point at pressure inside the head rather than at the eye.
• Call your child's team the same day if an eye becomes red, painful, or looks pushed forward, or the eye's position shifts suddenly. Also call for a temperature of 100.4°F (38°C) or higher during chemotherapy, which needs checking within hours, not overnight.
• Call your child's team within a day or two if you notice a white pupil in the other eye, a change in how the treated eye looks in photographs, a new head tilt, or unsteadiness on their feet.

Retinoblastoma, Childhood Cancer Survivorship, Genetic Testing for Cancer Risk, and Chemotherapy.

• https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq
• https://www.cancer.gov/types/retinoblastoma/patient/retinoblastoma-treatment-pdq