Retinoblastoma

• contiguous spread thru the choroid/sclera/orbit • extension along optic nerve into the brain • invasion of subarachnoid space/leptomeninges via CSF • hematogenous spread to bone, liver and spleen • lymphatic spread from the conjunctiva
 * **Epidemiolgy:** || Retinoblastoma is the most common intraocular tumor found in children. The frequency of retinoblastoma is one in 14,000 to one in 34,000 live births. The incidence of retinoblastoma is relatively low in the United States, about 300 cases per year. Retinoblastomas can occur in one or both eyes. The right eye is more commonly affected than the left eye. [1] ||
 * **Etiology:** || There are two classifications of the retinoblastomas, hereditary and in nonhereditary. In hereditary retinoblastomas, there is a mutation of chromosome 13, known as RB1 gene. This gene mutation causes retinoblastoma to develop and accounts for about 40% of all cases. The nonhereditary form of retinoblastomas commonly occurs bilaterally and accounts for 60% of all cases.[1] ||
 * **Signs & Symptoms:** || The most common signs of retinoblastoma is leukocoria, an abnormal appearance of the pupil, or cat’s eye reflex, a white pupillary reflex. Another common sign and symptoms is strabismus, a misalignment of the eyes, also known as “cross-eyes”. In advanced cases of retinoblastoma, eye enlargement is also commonly seen. [1] ||
 * **Diagnostic Procedures:** || Diagnostic procedures include a complete history, physical examination including a complete ophthalmologic examination, ultrasound for tumor location and size and a cranial CT scan. ||
 * **Histology:** || The tumor is composed mainly of undifferentiated anaplastic cells that arise from the nuclear layers of the retina. Histology shows similarity to other embryonic tumors such as neuroblastoma including features such as aggregation around blood vessels, necrosis and calcification.[2] ||
 * **Lymph node drainage:** || The affected regional lymph nodes include perauricular, submandibular and cervical lymph nodes. [3] ||
 * **Metastatic spread:** || There are five patterns of spread:[4]

The risk of metastases increases with tumor thickness and size.[4] || This is commonly used for the staging of the disease. ||
 * **Grading:** || There is no distinct grading system for retinoblastoma. However, the new International Classification of Intraocular Retinoblastoma is a logical flow of sequential tumor grading that linearly correlates with the outcome of newer therapeutic modalities. [4]
 * **Staging:** || AJCC Tumor Staging System [4]

T1/p1 T2/pT2 T3/pT3 T3a/pT3a T3b pT3B T3c pT3c T4/pT4 T4a pT4a T4b pT4b N1/pN1 M1

St. Jude’s Tumor Staging System

Stage I: Tumor (unifocal or multifocal) confined to retina a. Occupying one quadrant or less b. Occupying two quadrants or less c. Occupying more than 50% of retinal surface

Stage II: Tumor (unifocal or multifocal) confined to globe a. With vitreous seeding b. Extending to optic nerve head c. Extending to choroids d. Extending to choroids and optic nerve head e. Extending to emissaries

Stage III: Extraocular extension of tumor a. Extending beyond cut end of optic nerve (including subarachnoid extension) b. Extending through sclera into orbital contents c. Extending to choroids and beyond cut end of optic nerve (including subarachnoid extension) d. Extending through sclera into orbital contents and beyond cut end of optic nerve (including subarachnoid extension

Stage IV: Distant metastases a. Extending through optic nerve to brain

<25% of retina >25-50% of retina >50% of retina and/or intraocular beyond retina >50% of retina and/or cells in vitreous Optic disk Optic nerve up to lamina cribrosa Anterior chamber and/or uvea Anterior chamber and/or uvea and/or intrascleral Extraocular Optic nerve Beyond lamina cribrosa, not at resection line Other extraocular Other extraocular and/or at resection line Regional Distant metastases

b. Blood-borne metastases to soft tissue(s) and bone(s) c. Bone marrow metastases ||
 * **Radiation side effects:** || Radiation side effects of retinoblastoma include a high rise of EFFECTS: developing a second malignancy, modified vision, and cosmetic makeup of the face. Due to the high doses used (4000cGy) and the patient age (young) these patients are likely to have a decreased facial growth. As these patients age they will have small orbits and are more narrow through the temples. The patient may also experience blind spots. Radiotherapy may also cause: retinitis, dry eyes, and cataracts. [4] ||
 * **Prognosis:** || Poor prognostic factors include orbital invasion, involvement of the optic nerve, CNS dissemination, and heritable bilateral tumors. Size, growth patterns, and differentiation do not significantly impact prognosis. [4] ||
 * **Treatments:** || Enucleation is reserved for unilateral tumors in which the eye is no longer functional (blind). Radiation is the treatment of choice for less advanced tumors. Lens sparing techniques allow for the preservation of vision. Chemotherapy is useful for the reduction of tumor size. [4]

It is necessary to treat the entire retina to avoid recurrence of tumors. Field setups include single lateral field, a single anterior field, or a combination of lateral and anterior fields. Doses are 40-45 Gy in 1.5-2.0 Gy fractions with radiation alone. Combined with chemotherapy, doses are reduced to 35-40 Gy. [4] || Optic chiasm: 50 Gy Optic nerve: 50 Gy  Retina: 45 Gy [5] || [2] Lanzkowsky, P. //Manual of Pediatric Hematology and Oncology//. 5th ed. Burlington, MA: Academic Press; 2011. [3] Ramasubramanian A. //Retinoblastoma//. New Delhi, India: Jaypee-Highlights Medical Publishers, Inc; 2012. [4] Chao KS, Perez C, Brady L. //Radiation Oncology Management Decisions//. 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002. [5] Use of Normal Tissue Tolerance Doses Into Linear Quadratic Equation to Estimate Normal Tissue Complication Probability. Sanchez Cancer Center. http://www.rooj.com/Radiation%20Tissue%20Tolerance.htm. Accessed June 30, 2012. ||
 * **TD 5/5:** || Lens: 10 Gy
 * **References** || [1] Hoppe TR, Phillips LT, Roach M. //Leibel and Phillips Textbook of Radiation Oncology//. 3rd Edition. Philadelphia, PA: Elsevier; 2010.

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