Page 230 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

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Radiation Oncology

SUSAN M. LARUE AND IRA K. GORDON

Radiation therapy (RT) has been used to treat cancers in both cancers with what is referred to as “curative intent,” RT also plays
veterinary and human medicine since shortly after the discovery an important role in the palliative management of advanced can-
of x-rays by Roentgen in 1895, and the fields have followed simi- cers, the treatment of endocrinopathies associated with endo-
lar paths. Dr. Henri Coutard, a radiation oncologist at the Curie crine adenomas, as an adjuvant treatment for lymphoma, and for
Institute in Paris, carefully evaluated the effect of dose per frac- certain benign conditions. 12–19 New technology and treatment
tion, total dose, overall treatment time, field size, and tumor size approaches have led to an unwieldy collection of acronyms, the
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on tumor control and adverse radiation effects. Alois Pommer, an most common of which are listed in Table 13.1.
Austrian veterinarian, published extensively starting in the 1930s
on fractionated irradiation of benign and malignant diseases and Principles of Radiation Biology
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established an RT protocol widely used for many years. It was not
until the 1970s and 1980s that scientists acquired a broader under- Radiation dose is described by the amount of energy absorbed
standing of radiation biology, rationally explaining the benefit of by the tissue. The unit of absorbed dose is the Gray (Gy); 1 Gy
dividing dose into smaller fractions. Close to 60% of human equals one joule absorbed per kilogram of tissue. Ionizing radia-
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patients with serious cancers undergo RT at some point during tion kills cells by damaging critical molecules in the cell, primar-
treatment. Over the past 20 years, major technological advances ily deoxyribonucleic acid (DNA), which eventually leads to cell
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have improved tumor control and reduced adverse effects from death. Megavoltage photons, the predominant form of radiation
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irradiation. RT has also proven to be an effective treatment modal- used in veterinary medicine, interact with tissue primarily by the
ity for solid tumors in animal cancer patients; however, early use Compton effect, producing high energy electrons that cause ion-
of the newer modalities was limited due to the paucity of veteri- ization events either to critical molecules (direct action) or from
nary treatment centers. The past decade has been marked by the water molecules located within nanometers of critical molecules
opening of numerous veterinary RT centers and the commission- (indirect action). 21–25 These events produce highly reactive free
ing of more advanced RT technologies. Modalities, such as stereo- radicals that result in biologic damage that may kill the cell or
tactic RT (SRT), image-guided RT, and intensity-modulated RT render it incapable of reproducing. 20,25 This type of cell death,
(IMRT) have allowed more targeted treatment, decreasing adverse referred to as mitotic catastrophe, is due to chromosomal aberra-
radiation effects and providing improved radiation options for tions, primarily from double strand breaks. 20,26 Although mitotic
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tumors in a variety of locations. More than 70 facilities in North death is still the primary mode of radiation-associated cell death,
America are actively treating animals with RT and 27 of those other mechanisms have been recognized, including apoptosis,
reporting SRT capabilities. The American College of Veterinary radiation bystander effect, radiation abscopal effect, autophagy,
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Radiology (specialty in radiation oncology) has residency training and senescence.
programs at 13 treatment centers. International expansion has
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included Europe, Asia, Australia, and South America. 6 Repair of Radiation-Induced DNA Damage
The management of cancer patients is complex, and determin-
ing the best treatment modality or combination of modalities can A critical determinant of a cell population’s sensitivity to radiation
be challenging. In most instances, when local control of a solid is the ability of cells to repair DNA damage caused by radiation.
tumor cannot be obtained surgically without excessively compro- 1 Gy of radiation from photons causes approximately 2500 base
mising function, appearance, or quality of life, consultation with damages, 1000 single strand breaks, and 40 double strand breaks
a radiation oncologist is advised. Surgery followed or preceded by in DNA in each cell. Mammals have developed highly conserved
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fractionated RT may allow a more conservative surgery and yield pathways to sense and repair single and double strand breaks as
comparable or better tumor control and/or functional outcome well as other forms of DNA damage. 27,28 The double strand breaks
than either surgery or RT alone. RT alone is indicated in areas are the most lethal as they may lead to severe chromosomal aber-
where surgical options are limited, such as nasal tumors, heart- rations. 20,28 Most of this damage is repaired by cells within 6 to
based tumors, and some brain tumors. 8–10 SRT has provided treat- 24 hours. 29,30 Genes involved in control of intrinsic radiosensi-
ment alternatives in patients where surgery is not an option and tivity are primarily genes involved in cell-cycle progression and
in locations that were not previously amenable to unmodulated DNA repair. 31,32 A given dose of radiation is preferentially cyto-
RT, such as abdominal tumors. In addition to treating serious toxic to proliferating cells, including tumor cells and renewing cell
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