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Radiotherapy for Ocular Tumours C Stannard Et Al 120 Eye (2013) 27, 119–127 & 2013 Macmillan Publishers Limited All rights reserved 0950-222X/13 www.nature.com/eye CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM Radiotherapy for C Stannard1, W Sauerwein2, G Maree3 and K Lecuona4 ocular tumours Abstract Introduction Ocular tumours present a therapeutic Ocular tumours tend to cause loss of vision and challenge because of the sensitive tissues the development of an inflamed and painful involved and the necessity to destroy the eye. Malignant tumours also threaten patients tumour while minimising visual loss. with death from local spread or metastatic Radiotherapy (RT) is one of several disease. modalites used apart from surgery, laser, Ocular treatment is aimed at conserving the cryotherapy, and chemotherapy. Both eye with as much useful vision as possible external beam RT (EBRT) and brachytherapy while eradicating any risk to life. Most are used. Tumours of the bulbar conjunctiva, ocular tumours are treated with some form squamous carcinoma and malignant of radiotherapy (RT). melanoma, can be treated with a radioactive Ionising radiation is highly effective plaque: strontium-90, ruthenium-106 therapeutically, but is also harmful to healthy (Ru-106), or iodine-125 (I-125), after excision. tissues. It is therefore necessary to administer a If the tumour involves the fornix or tarsal sufficiently high dose of radiation to the conjunctiva, proton therapy can treat the tumour while minimising the collateral conjunctiva and spare most of the eye. damage to adjacent tissues. 1 Alternatively, an I-125 interstitial implant Department of Radiation There are several types of ionising radiation, Oncology, Groote Schuur can be used with shielding of the cornea and which can be delivered by a variety of Hospital and University of lens. Conjunctival mucosal-associated techniques and with a selection of protocols. Cape Town, Cape Town, South Africa lymphoid tissue lymphoma can be treated These have advanced significantly over the past with an anterior electron field with lens decades so that the current range of therapeutic 2Department of Strahlenklinik, shielding and 25–30 Gray (Gy) in 2 Gy options can be confusing to non-specialists. Universitstsklinikum Essen, Universitat Duisberg-Essen, fractions. Discrete retinoblastoma (RB), too In this review we describe ionising radiation, Essen, Germany large for cryotherapy or thermolaser, or how this is delivered to the eye and how recurrent after these modalities, can be different ocular tumours are irradiated. 3Department of Medical Physics, treated with plaque therapy, I-125, or Ru-106. Groote Schuur Hospital and University of Cape Town, For large RB, multiple tumours, or vitreous Cape Town, South Africa seeds the whole eye can be treated with an Ionising radiation 4 I-125 applicator, sparing the bony orbit, or Department of Ophthalmology, Ionising radiation can be classified as Groote Schuur Hospital and with EBRT, under anaesthetic, using X-rays University of Cape Town, electromagnetic or particulate. or proton therapy with vacuum contact Cape Town, South Africa lenses to fix the eyes in the required Correspondence: position. Post-enucleated orbits at risk for Electromagnetic radiation C Stannard, Division of recurrent RB can be treated with an I-125 Radiation Oncology, Department implant with shielding to reduce the dose to of Radiation Medicine, Groote Electromagnetic radiation includes X-rays and Schuur Hospital, Observatory, the bony orbit. Uveal malignant melanomas g-rays. These are physically identical in nature Cape Town, Western Cape 7925, can be treated with plaque or proton therapy and properties but differ in the way they South Africa Tel: þ 27 21 404 4271; with excellent local control. Preservation of are produced. Fax: þ 27 21 404 5259. vision will depend on the initial size and X-rays are produced in an electrical device E-mail: [email protected] location of the tumour. that accelerates electrons to high energy, Received: 5 October 2012 Eye (2013) 27, 119–127; doi:10.1038/eye.2012.241; directing them on to a target such as tungsten. Accepted: 8 October 2012 published online 23 November 2012 Part of the kinetic energy of the electrons is Published online: converted into X-rays.1 Low-energy X-rays, 23 November 2012 100–250 kV, are produced in an X-ray tube. This paper was presented at the Cambridge Keywords: radiotherapy; ocular tumours; High energy X-rays, 4–18 MV, are produced Ophthalmology Symposium. brachytherapy; iodine-125; proton therapy by a linear accelerator (linac). 13–14 September 2012. Radiotherapy for ocular tumours C Stannard et al 120 g-rays are emitted by radioactive isotopes as the unstable nucleus breaks up and decays in an attempt to reach a stable form. Isotopes used in ophthalmology include cobalt-60 (Co-60), iridium-192 (Ir-192), and iodine-125 (I-125). Particulate radiation Particulate radiations occur in nature and include electrons, protons, neutrons, a-particles, negative p mesons, and heavy charged ions. High-energy electrons are accelerated in a linear accelerator and emerge without impinging on a target. They are less penetrating than X-rays because of their low mass. b-rays are physically identical to electrons but are Figure 1 Depth dose curves for different radiation beams. Courtesy of Professor Dan Jones, iThemba LABS, Faure, emitted from radioactive isotopes as they decay, for Cape Town. example, Strontium-90 (Sr-90), ruthenium-106 (Ru-106). Therapeutic protons are produced by accelerating protons in a cyclotron. 120 SOBP 100 Radiation techniques RT is described according to whether the source of 80 radiation is far (tele) or near (brachy) the target tissue. 60 Teletherapy Relative dose 40 Teletherapy, otherwise known as external beam RT 20 (EBRT), includes X-rays, Co-60 g-rays, and electrons. Increasingly sophisticated methods of delivering RT have 0 0 510152025 been developed to reduce the dose to surrounding Depth in water / cm normal tissues while maintaining a tumouricidal dose to the tumour. These include: (a) single or multiple Figure 2 Spread out Bragg peak (SOBP) of a proton beam. collimated (shaped) fields; (b) three-dimensional Courtesy of Professor Dan Jones, iThemba LABS, Faure, Cape Town. conformal RT (computerised tomograhic planning, each field individually shaped); (c) intensity modulated RT (multiple fields, static or dynamic gantry, inverse important consideration when treating children, to planning to treat the target volume to full dose while minimise the risk of second malignancies. restricting the dose to sensitive structures, and variation Stereotactic radiation may be delivered with a g-knife in intensity within each beam with a multileaf collimator (multiple Co-60 sources in a helmet), stereotactic linac to achieve this); and (d) stereotactic RT (multiple shaped (multiple arcs of beams), and cyberknife (a more mobile beams or arcs all concentrating on the target volume). linac with small beams). All of the above are much more The patient must be immobilised to allow accurate expensive than conventional RT, and the integral dose delineation of the target volume, planning the shape is greater than with proton therapy. and direction of the beams, and accurate treatment Treatment is usually delivered in multiple small delivery. fractions over a period of weeks. This increases tumour Proton therapy uses the spread out Bragg peak, which damage by allowing time for reoxygenation and has a sharp lateral penumbra and no exit dose (Figures 1 reassortment of cells in the cell cycle making them more and 2). This results in tight conformity to the tumour sensitive to RT. It also spares normal tissues by allowing with minimal dose to the surrounding normal tissues. time for sublethal damage to be repaired in between The integral dose, which is the total dose to normal fractions.1 Conversely, stereotactic RT or proton therapy tissues, is lowest with proton therapy. This is an is delivered in one or a few large fractions, but to small Eye Radiotherapy for ocular tumours C Stannard et al 121 discrete volumes, thus minimising the volume of RT techniques for different sites surrounding normal tissue irradiated. Conjunctiva Bulbar conjunctiva The most common malignant tumours of the bulbar conjunctiva are squamous cell Brachytherapy carcinoma and malignant melanoma (Figure 3). The Brachytherapy is the placing of radioactive sources close standard treatment for these tumours is excision together to or into a tumour. Localised RT for uveal melanoma with adjunctive therapy consisting of cryotherapy, and retinoblastoma (RB) was initiated by Moore et al2,3 chemotherapy, or RT. RT is usually delayed until the using radon seeds, Subsequently, Stallard4 developed conjunctiva has healed. radioactive applicators using radium-226. These were RT can be administered with a hand-held Sr-90 later superseded by Co-60 plaques.5 Lommatsch was the applicator delivering 60 Gy to the surface in four first to use Ru-106 plaques6 and Sealy et al7 was the first fractions once a week or 50 Gy in five daily fractions. to use I-125 to treat ophthalmic tumours. Table 1 shows Such treatment yields excellent rates of local control the characteristics of the various isotopes used, including for squamous cell carcinoma, with minimal morbidity, whether b or g emitters, the half-life (time taken to decay provided that the plaque is sufficiently large to to half the activity), energy, half value layer in tissue encompass the entire tumour bed (Figure 4).8 Tumours (mm of tissue required to reduce the energy to half), that are larger than the available applicator, or those that useful range in tissue, sclera to apex dose, and the penetrate the sclera, are best treated with a custom-made amount of lead (Pb) required to block the radiation I-125 plaque giving 60 Gy at 2–3 mm (Figure 5). The dose by 95%. Brachytherapy can be delivered by means given for conjunctival melanoma after excision is 100 Gy of plaques, applicators, and interstitial implants. in 4 weekly fractions of 25 Gy.
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