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    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    1 Update on General Medicine

    Chapter 13: Cancer

    Radiation Therapy

    Radiation therapy, which uses ionizing radiation to kill cancer cells and shrink tumors, is part of the treatment plan for many patients with cancer. Ionizing radiation interacts with tissues via an energy transfer and a chemical reaction, in which free radicals are released and water molecules decompose into hydrogen, hydroxyl, and perhydroxyl ionic forms. These ionic forms break atomic and molecular bonds, which in turn break the double-stranded DNA structure and cause cellular death. Consequent cell death occurs in both normal tissue and malignant lesions. In radiotherapy, biochemical recovery and biologic repair occur in the normal host cells, maintaining the integrity of vital systems.

    In radiation oncology, therapeutic ratio refers to a fundamental concept in which the risks and benefits to the targeted cancer cells and the surrounding tissues must be weighed. Lymphocytes are damaged by 1 gray (Gy) of radiation and central nervous system tissue by 50 Gy. Table 13-2 lists some examples of the effects of radiation on ocular and nonocular tissues.

    Radiation can be delivered through external beam radiotherapy (EBRT; most common) or internal placement (brachytherapy); radiation can also be administered systemically (eg, radioactive substance bound to a monoclonal antibody). In EBRT, high-energy x-ray beams generated either by linear accelerators, which produce photons or electrons, or by cobalt machines, which use radioactive decay of an element such as cobalt 60, are aimed at the tumor site. Planning for EBRT involves not only localizing the tumor, but also determining the proper dose of radiation: one that will kill the malignant cells while minimizing damage to the surrounding noncancerous tissue. There are many other methods of EBRT, including particle therapy and stereotactic radiosurgery.

    Table 13-2 Radiation Damage to Ocular and Nonocular Tissues

    In brachytherapy (also called internal radiation therapy), radioactive material is implanted within or adjacent to the tumor, delivering radiation while minimizing damage to the surrounding normal tissue. The term brachytherapy refers to various types of procedures, one example of which is seed implantation, used in the treatment of prostate cancer and some uveal melanomas. See BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors, for more on brachytherapy and uveal melanomas.

    For some conditions, monoclonal antibodies are available as a vector to deliver radiation directly to the target tissue; these antibodies are discussed later in this chapter in the section Biologic Therapies.

    • Jeganathan VS, Wirth A, MacManus MP. Ocular risks from orbital and periorbital radiation therapy: a critical review. Int J Radiat Oncol Biol Phys. 2011;79(3):650–659.

    Ophthalmic considerations The ocular effects of irradiation depend not only on total dose, fractionation, and treatment portal size but also on the presence of any associated systemic diseases such as diabetes mellitus and hypertension. Concomitant chemotherapy has an additive effect.

    The lens is the most radiosensitive structure in the eye, followed by the cornea, the retina, and the optic nerve. The orbit is completely included in the treatment portal in diseases such as large retinoblastomas; it is partially included in tumors of adjacent structures, such as the maxillary antrum, nasopharynx, ethmoid sinus, and nasal cavity. Usual radiation doses range from 20 to 100 Gy. The total dose is usually fractionated into smaller doses during the treatment. In brachytherapy, a low-energy isotope such as radioactive iodine delivers a high dose of radiation within a few millimeters of the tumor but does not penetrate deep into it. This allows for radioactive episcleral implants to deliver a dose of 100 Gy to the apex of a tumor but a much lower dose to the rest of the eye. The sclera can tolerate doses up to 400–800 Gy.

    Doses to the lens as low as 2 Gy in a single fraction may cause cataract formation. However, cataracts caused by low doses may be asymptomatic and may not progress. Cataracts resulting from higher doses (7–8 Gy) may continue to progress, resulting in considerable vision loss. The average latent period for the development of radiation-induced cataracts is 2–3 years.

    The clinical picture of radiation retinopathy resembles that of diabetic retinopathy. The usual interval between radiation therapy and the development of radiation-induced retinopathy is 2–3 years. Radiation retinopathy may develop earlier in patients with diabetes mellitus or in those undergoing chemotherapy. The earliest clinical manifestation of radiation retinopathy is usually cotton-wool spots. After several months, these spots fade away, leaving areas of capillary nonperfusion. Telangiectatic vessels grow from the retina into these areas. Microaneurysms may also develop. These ischemic changes may cause neovascularization of the iris, which in turn may lead to neovascular glaucoma. The capillary endothelial cell is the first type of cell to be damaged, followed closely by the pericytes and then the endothelial cells of the larger vessels. The new intraretinal telangiectatic vessels have thick collagenous walls. There may be spotty occlusion of the choriocapillaris. Panretinal photocoagulation or injection with anti–vascular endothelial growth factor (anti-VEGF) agents are effective treatments for radiation retinopathy. See BCSC Section 12, Retina and Vitreous, for more on this topic.

    Radiation optic neuropathy may present with optic nerve head pallor with splinter hemorrhages. Injury to the more proximal part of the optic nerve resembles retrobulbar optic neuropathy. Affected patients may report unilateral headaches and ocular pain; the optic nerve head may not reveal edema or hemorrhage. With doses of 60–70 Gy, dry eye syndrome sometimes develops. This syndrome usually develops within a year and occasionally progresses to corneal ulceration and severe pain. For more on radiation optic neuropathy, see BCSC Section 5, Neuro-Ophthalmology.

    Ocular manifestations of fetal irradiation in the first trimester include microphthalmos, congenital cataracts, and retinal dysplasia.

    Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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    2022-2023 Basic and Clinical Science Course, Complete Print Set
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    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
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