International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: eyeLocalized whole eye radiotherapy for retinoblastoma using a 125I applicator, “claws”
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.
Section snippets
Methods and materials
The applicator consists of a gold pericorneal ring, 4.5 mm wide, the surface of which is curved to conform to the surface of the eye. The inner diameter is 11 mm and the outer diameter 18 mm. Four triangular pieces of gold are glued on at the 3, 6, 9, and 12-o’clock positions. There are 8 pairs of holes, 4 pairs through the ring and each triangular piece and 4 pairs between each of the triangular pieces at the 1:30, 4:30, 7:30, and 10:30-o’clock positions (Fig. 1). The ring is attached to the
Results
Twenty-nine eyes were treated, 5 patients were lost to follow-up, and 24 eyes were followed for 2–157 months. Eighteen of these had Group V tumors.
Local control of retinoblastoma is recognized by various regression patterns: I, calcification; II, fish flesh; III, fish flesh plus calcification; and IV, disappearance of tumor (32). These are shown for each eye in Table 1.
Local control was achieved with the applicator alone in 7 patients for 2–74 months. In 3 other patients, the treated tumors
Discussion
Concern about the late effects of RT in very young children, including cosmetic, functional, and second nonocular malignancies, has led to improvements in the variety of techniques used to treat the whole eye in children with tumors beyond local methods of treatment but still with a chance of control and preservation of vision. These include rotating plaques (14), proton therapy (29), chemotherapy 24, 25, 26, 27 with or without additional focal treatment, chemotherapy with photodynamic therapy
Summary
The 125I applicator is a novel method of delivering RT to the whole eye while sparing the surrounding structures. It should therefore reduce the chance of late cosmetic deformities and second nonocular malignancies. It is simple to apply once the initial design and calculations have been done, the treatment time is short, and it is cost effective when used in a center that uses 125I regularly. Its use in combination with chemotherapy for advanced disease may improve the visual outcome in
Acknowledgements
I thank Mrs. Hazel Hogg for typing the manuscript and table, Dr. Peter Mitchell, Chief Medical Superintendent, Groote Schuur Hospital, for permission to publish this article, and all the referring physicians.
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Deceased.