Localized whole eye radiotherapy for retinoblastoma using a ¹²⁵I applicator, “claws”

Abstract

$\text{Purpose:}$ To treat children with retinoblastoma, who require whole eye radiotherapy, with a specially designed ¹²⁵I applicator that irradiates the eye while sparing the surrounding tissues.

$\text{Methods and Materials:}$ Under general anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4 appendages, each loaded with ¹²⁵I seeds, are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and 11 received 40 Gy during 122 hours, when the relative biologic effectiveness was taken as 1 instead of 1.5. Six had received prior chemotherapy.

$\text{Results:}$ Twenty-four eyes were followed up for 2–157 months (median 29). Although 22 eyes responded, local control was achieved in 13 patients, 3 of whom required additional treatment for new tumors; a further 3 required additional treatment for tumor recurrence as well as new tumors. One of these eyes was enucleated for neovascular glaucoma. All 6 Group I–III eyes and 6 of 18 Group V eyes were retained for 2–157 months (median 39), with good vision in 10 eyes. Three developed cataracts 7, 8, and 12 years later, 1 of which has been removed.

$\text{Conclusions:}$ This is a new way of irradiating the whole eye with a minimal dose to the surrounding tissues. The treatment time is only 5 days. It is effective in Groups I–III, but only 33% of Group V eyes retained vision. No late cosmetic defects occurred.

Introduction

Retinoblastoma is the most common intraocular tumor of childhood, occurring in 1 in 10,000 to 1 in 34,000 new births (1). It is bilateral in 25–33% of cases and is associated with the absence of the retinoblastoma gene on both alleles of chromosome 13 (2). The first mutation may be somatic or germinal, or inherited from an affected parent; the latter 2 are more likely to produce bilateral disease. The survival of patients in developed countries is about 90% 3, 4, 5, and it is likely that the inherited form of the disease will increase. In developing countries, the survival may be reduced to 60% 6, 7, as presentation occurs much later and the disease may be advanced.

Children with unilateral disease usually present with advanced intraocular disease, and the eye is invariably enucleated. Those with bilateral disease present at an earlier age (7), usually <2 years old, and the disease is often more advanced in 1 eye than in the other. Each eye should be assessed individually as to whether it can be treated conservatively and if so with which modality.

Eyes with Group I–IV Reese-Ellsworth staging (8) can be treated conservatively. However, for those with Group V staging, one must ascertain whether any visual potential is present. An eye that is blind, filled with tumor, has complete retinal detachment, panophthalmitis, or any indication of extraocular tumor should be enucleated. However, conservative treatment should be given to those eyes with some vision and some normal retina, despite the presence of large tumors and/or vitreous seeding.

Conservative treatment of intraocular tumors consists of cryotherapy, laser coagulation, transpupillary thermotherapy, episcleral plaque therapy, whole eye radiotherapy (RT), chemotherapy, thermochemotherapy, and chemotherapy with photodynamic therapy.

Cryotherapy 9, 10, and photocoagulation (11) or laser therapy and transpupillary thermotherapy (12) are used for small tumors, usually not exceeding 3–4 mm in diameter and 2 mm in height. Episcleral plaques, ¹²⁵I 13, 14, and ¹⁰⁶Ru (15) can be used for larger, discrete tumors. If vitreous seeding is present, or if the tumors are multiple or large and cannot easily be treated by local methods, one of the other methods should be used to preserve the eye and vision. Conventional whole eye RT is usually given with mega-voltage X-rays. Half-beam blocked lateral fields (5) or lateral oblique photon fields and a lateral electron field (for unilateral tumors) (5) or a lateral field with an anterior photon (16) or electron field (5) with lens shielding are used. Alternatively, the Schipper technique 17, 18, which uses beam splitting and an extended D-shaped collimator to which are directly linked rods from contact lenses that maintain the position of the lens relative to the beam, can be used. This minimizes the dose to the lens and the subsequent risk of developing a cataract and/or damage to the anterior eye and eyelids, but may result in underdosing the anterior retina. However, the surrounding bony orbit and part of the lacrimal gland are also irradiated with any of the above techniques, and, not only does this result in reduced growth of the orbit, facial asymmetry 19, 20, and possibly a dry eye (21), there is considerable concern about the development of subsequent nonocular malignancies in children with germline retinoblastoma gene mutations (22). The incidence of these second malignancies increases with time after irradiation, reaching 35% at 30 years, and also occurs at an earlier age in those who undergo irradiation at <1 year of age (23).

Chemotherapy is being used more frequently for intraocular disease in an attempt to avoid enucleation and reduce the extent of RT or delay its administration until the child is older 12, 24, 25, 26, 27, but it usually requires consolidation with other methods to prevent recurrence. Chemotherapy and photodynamic therapy (28), as well as thermochemotherapy (26), and more recently, proton therapy, have been used to reduce the dose to the surrounding tissues (29). ¹²⁵) is an X-ray and gamma-ray-emitting isotope with an energy of 27–35 keV and half life of 60.2 days. It is available in seed form measuring 4.5 × 0.75 mm. It is thus ideal for treating ophthalmic tumors. A flexible system for treating these has been developed by one of us (R.S.) at Groote Schuur Hospital, Cape Town 30, 31 since 1974. In 1987, an ¹²⁵I applicator was designed (by R.S.) to irradiate the contents of the eye while sparing the surrounding bone and soft tissues. We describe our experiences with this applicator.