•Etoposide is known to carry a risk of myelodysplasia or myeloid leukemia, presently estimated to be <2–3% at the cumulative etoposide dosage used for retinoblastoma. There a few reported cases of retinoblastoma with acute myeloid leukemia after CEV chemotherapy [48–50]. Greater intensity of exposure (daily or weekly, rather than 3-weekly), concurrent use of alkylating agents or other topoisomerase II inhibitors like anthracyclines or radiation, may be major factors in children treated for other cancers [51].

9.14.7  Related SOPs

SURG central line; SURG Omaya reservoir; CHEM IIRC C&D; CHEM IIRC B; CHEM extraocular CNS; CHEM extraocular orbit; CHEM metastatic; CHEM intrathecal.

9.15  Radiation SOP

9.15.1  Objective

Radiation to cure retinoblastoma refractory to first-line chemotherapy with focal therapy.

9.15.4  Clinical Significance

•Radiation has cured many eyes with intraocular retinoblastoma, but with very severe consequences, so that it is largely reserved for second-line rescue after chemotherapy with failed focal therapy, and in conjunction with chemotherapy for orbital recurrences.

•Episcleral radioactive plaques (radioactive iodine or ruthenium) are particularly useful for smaller solitary tumors which are not adjacent to the macula or the optic nerve, or for unifocal tumor recurrences after full cycles of chemotherapy or external beam irradiation, when a second radiation course to the whole globe will lead to severe radiation damage.

9.15.5  Procedure

•External beam radiation, 3,500–4,000 cGy, is administered over a 3–4 week period.

•Stereotactic or focused proton beam can reduce bone-dose and the risk of induction of second malignancy [52].

•For brachytherapy, a radioactive plaque is inserted under general anesthesia, on the sclera opposite to the tumor, and left until the prescribed radiation dose is delivered to the apex of the tumor.

9.15.2  Applicability

Radiotherapist, oncologist, ophthalmologist

9.15.3  Scope

External beam radiation for the last eye after chemotherapy and focal therapy failure to control tumor; orbital radiation for orbital recurrence postenucleation; brachytherapy as a primary treatment for isolated unifocal tumor not adjacent to the nerve or macula.

9.15.6  Consequences

•Post-relapse salvage with external beam radiation is effective, but some children still ultimately require enucleation of the last remaining eye.

•The risk of second malignancies is >50% by age 50 in children with germline RB1 mutant alleles treated with external beam radiation [53], particularly in children treated when younger than 1 year of age [54].

•Facial asymmetry secondary to orbital growth disturbance, or enophthalmos due to orbital fat necrosis, may develop in children irradiated at a young age.

•Cataracts may occur after frontal-field radiation.