Treatment of Intraocular Retinoblastoma

Systemic Chemotherapy

For intraocular retinoblastoma, chemotherapy is used in a neoadjuvant setting, often in combination with local ophthalmic therapies, where its purpose is to decrease tumor size and volume to allow the successful utilization of local ophthalmic therapies. In this setting, it is often referred to as chemoreduction. Systemic chemotherapy can also be used in combination with enucleation, where one eye is enucleated and chemotherapy is delivered to treat tumors in the remaining eye. Chemotherapy regimens generally include vincristine, etoposide, and carboplatin (Table 23-4).

External Beam Radiotherapy

Standard of care for intraocular retinoblastoma for many years has included external beam radiotherapy with doses of 40-45 Gy. This resulted in a number of late effects and increased risk of second malignancies both in and out of the field of radiotherapy. Newer methods of delivering radiotherapy with more conformal fields are being used at present, so that the normal structures receive less scatter and thus the risk for

Table 23-4. Adjuvant Chemotherapy Protocol for Intraocular Retinoblastoma"

Six cycles of the following are given every 28 days:

Vincristine 0.05 mg/kg (1.5 mg/m2 if >age 3 years) on day 1 Carboplatin 18.6 mg/kg (360 mg/m2 if >age 3 years) on day 1 Etoposide 5 mg/kg (150 mg/m2 if >age 3 years) on days 1 and 2

"Ongoing protocols are evaluating the utility of higher doses of carboplatin and etoposide for patients with group C or D disease. Ongoing protocols for patients with group B disease are evaluating the elimination of etoposide from this regimen. There are other protocols that include cyclosporin A aimed at decreasing drug resistance.

adverse long-term outcomes will be less. Conformal radiotherapy, stereotactic radiotherapy, proton beam radiotherapy, and intensity-modulated radiation therapy all use technology that minimizes doses to nontarget structures. In addition, there are current protocols testing doses of 23-36 Gy with encouraging results. Increased risk of secondary malignancy is reduced when radiation is given after 1 year of age to children with retinoblastoma. The use of systemic neoadjuvant chemotherapy may allow delay of external beam radiotherapy to until after 1 year of age.

Local Ophthalmic Therapies

Local therapy is used to eradicate local disease after reduction of the tumor volume by chemotherapy and may include cryotherapy, green laser, infrared laser, and/or radioactive plaque. The goal of local therapy is to achieve a type I regression pattern with calcification or type IV with flat chorioretinal scars, or avascular, linear, white gliosis.

Cryoablation

Cryotherapy can be utilized after chemotherapy for ablating tumor remnants/recurrences up to 3 mm in height that are located at or anterior to the equator. It is recommended that no more than four different sites be frozen in one eye at a single session. There is less likelihood of creating vitreous seeds with cryotherapy if a tumor has been previously treated with chemotherapy. Extensive cryotherapy has been associated with significant persistent retinal detachment, particularly if the retina was originally detached prior to chemotherapy. Retinal breaks can be caused by cryotherapy.

Green Laser Photoablation

Green laser (argon or 532-nm frequency-doubled YAG) photoablation can be used to directly coagulate tumors up to 8 mm in thickness, especially posterior to the equator following chemotherapy. The tumor is outlined with burns half on and half off the retina. There should be a 30% spot overlap. After outlining the tumor, the entire tumor should be covered with 30% overlapping spots. Complete coverage is considered "one laser treatment." Each numbered lesion should receive a minimum of three complete "laser treatments" with only one "complete laser treatment" given at each session. Laser-induced hemorrhage has been associated with vitreous seeding. Inadequate dilation of the pupil can cause laser burns to the iris.

Infrared Laser Photoablation

Infrared laser photoablation can be selected to treat tumors up to 8 mm in thickness that have an intact retinal pigment epithelium following chemoreduction. The use of excessive power may result in hemorrhage or vitreous dissemination of tumor, but starting with low power and gradually increasing avoids these problems.

Episcleral Plaque Radiotherapy

Plaque radiotherapy may be used to treat local recurrences up to 8 mm in thickness and 15 mm in base. Iodine-125 or ruthenium-106 can be utilized for plaques. The tumor dose is prescribed at the apex of the tumor. The total dose to the tumor apex is 30-35 Gy. Proliferative retinopathy secondary to plaque can occur.

Subtenon Chemotherapy

For patients with more advanced intraocular disease (Resse-Ellsworth group V; international classification groups C and D), pilot studies have been conducted using subtenon carboplatin in addition to systemic chemotherapy and other local ophthalmic therapies. The ophthalmologist makes a 3-mm incision in the conjunctiva and anterior tenons. A 5-cc syringe containing the carboplatin is fitted with an olive-tip irrigating cannula. The olive-tip cannula is placed through the conjunctival incision and is gently and bluntly passed through the posterior tenon's capsule while maintaining constant contact with the globe. Once the irrigating cannula has been passed posteriorly to its full extent, the opening in the conjunctiva and tenons is pulled tightly over the shank of the needle with a forceps and the carboplatin is slowly delivered into the retrobulbar space by gentle pressure on the syringe plunger. The cannula is withdrawn once the retrobulbar injection is complete. No sutures are necessary on the conjunctival incision but that is the surgeon's choice. A combination antibiotic ointment should be instilled into the conjunctival sac on completion of the injection. While the early results of such studies are promising, larger trials are required to fully evaluate efficacy.

Enucleation

Enucleation of the eye is recommended when there is no chance for useful vision even if the entire tumor is destroyed. It is also indicated with high features where risk of development of extraocular or metastatic disease is high.

Careful examination of the enucleated specimen by an experienced pathologist is necessary to determine if high-risk features for metastatic disease are present. These include:

1. Anterior chamber seeding

2. Choroidal involvement

3. Tumor beyond the lamina cribrosa

4. Intraocular hemorrhage or

5. Scleral and extrascleral extension.

External beam radiotherapy or systemic adjuvant therapy is generally required in patients with certain high-risk features assessed by pathologic review after enucle-ation to prevent the development of metastatic disease. Adjuvant therapy with external beam radiotherapy and chemotherapy is required if there is tumor at the cut end of the optic nerve.

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