Retinoblastoma is a tumor of the eye that typically occurs in children less than 6 years old. The tumor starts in the retina, which is the back of the eye, behind the pupil. In some children both eyes are affected. Retinoblastoma can run in families, and so it is important that parents, siblings, and offspring of a patient with retinoblastoma be evaluated by an ophthalmologist. Some patients with retinoblastoma involving both eyes also have a tumor in their pineal gland deep within their brain. Patients who survive bilateral retinoblastoma as a child are at risk for additional cancers, including osteosarcoma, as they get older.

Retinoblastoma Symptoms

Signs or symptoms concerning for Retinoblastoma include:

• a white pupil (can also be caused by Toxocara infection, oxygen exposure as a premature infant, cataract, or retinal detachment)
• worsening vision over weeks to months
• development of misaligned eyes over weeks to months
• change in pupil size

Retinoblastoma Diagnostic Testing and Surgery

After a careful history and physical examination, we typically obtain:?

• MRI of the eyes and brain
• an eye exam under anesthesia by the opthalmologist (biopsy of the tumor is not necessary if it has the classic appearance of a retinoblastoma)
• blood tests to measure blood counts and liver and kidney function
• baseline hearing and kidney tests if chemotherapy is being considered
• consultation with a surgeon for central line placement if chemotherapy will be used
• additional tests for tumor spread (spinal tap, bone marrow evaluation, CT scan of chest and abdomen) are usually not needed, unless the tumor has grown outside the eye
• radiation therapy consult in case this modality is needed

Retinoblastoma Staging

Based on the results of opthalmologist examination, a clinical group will be assigned to each eye:

• Group A:tumor 3 mm or smaller and confined to the retina but not near the optic disc or fovea (the central area of the retina)
• Group B: all other tumors still confined to the retina
• Group C: tumor starts in the retina but has spread locally to produce fluid under the retina or small tumor seeds in the fluid of the eyeball?
• Group D: tumor has spread throughout the retina and eyeball, but not to the lens
• Group E: tumor reaches the lens or pupil muscles, may cause glaucoma, may infiltrate the wall of the eyeball

If there is spread outside the eye, then a Stage is assigned:

• Stage 2-patients who had eye removal (enucleation) and tumor was found at the cut edge of the optic nerve or infiltrating the sclera (outer layer of eyeball)
• Stage 3-tumor spread outside the eye to the orbit or nearby lymph nodes
• Stage 4a-spread distantly (bone marrow, lymph nodes, bone, liver), but not brain
• Stage 4b-spread distantly includes the spinal fluid or brain

Retinoblastoma Therapy

Therapy is based on whether the tumor involves one or both eyes and on the Stage. Patients are given the opportunity to enroll on Children's Oncology Group therapy protocols or may choose to be treated off protocol with standard of care therapy.

Unilateral, one-sided tumors that have not spread outside the eye:

• If the opthalmologist feels that useful vision cannot be obtained, then removal of the eye (enucleation) is recommended
• If the tumor(s) are small enough, the opthalmologist may offer local therapies such as laser therapy or cryotherapy (freezing the tumor) or eye conjunctiva injections with chemotherapy (Subtenon) in an effort to save the eye
• If the tumor(s) are too large for local therapies alone, then although removal of the eye has been the standard therapy, we will offer use of chemotherapy (with carboplatin and vincristine, with or without etoposide) combined with local therapies in an effort to save the eye. There is a small risk that this chemotherapy will cause a second cancer or damage the hearing or kidneys.
• If these therapies are not successful, or if parents prefer to avoid chemotherapy, then enucleation is performed (radiation is avoided due to its risks of causing cancer or bone growth abnormalities)

Bilateral tumors that have not spread outside the eye:

For any eye for which useful vision cannot be salvaged then enucleation will be needed chemotherapy and local control measures described above are offered if these therapies are not successful, then radiation therapy is offered to try to save vision.

Spread outside the eye:

Chemotherapy will be offered, potentially combined with an autologous stem cell transplant to allow use of higher doses

Prognosis

Useful vision is obtained using local control or chemotherapy without radiation in approximately 91% of Group A, 84% of Group B, 60% of Group C, and 30% of Group D eyes. Addition of radiation has the potential to save a subset of Group E eyes.

About 90% of Stage 2 and 40% of Stage 3 patients are cured with chemotherapy. 40% of Stage 4 patients have achieved prolong remission in initial studies using stem cell transplant.

Therapy for Relapse

• Patients with unilateral tumors that recur after local therapies are candidates for chemotherapy, with enucleation another option.
• Patients with bilateral tumors that recur within the eye are candidates for radiation therapy, with enucleation another option.
• Patients that recur outside the eye are candidates for chemotherapy, including higher doses with stem cell transplantation.

Long-term Evaluation

Patients are followed for recurrence by the opthalmologist with frequent examinations under anesthesia and by history and physical examinations.? MRI of the eyes and brain will be done periodically. Hearing tests, blood counts, and liver and kidney function will be followed if chemotherapy was given.