Page 233 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

212 PART III Therapeutic Modalities for the Cancer Patient

be unpleasant for the patient and distressing to the owner, and
Tumor
control in rare instances they can be life-threatening if proper care is
not given. Acute effects will heal with modest pain manage-
VetBooks.ir 80 Late ment in the vast majority of cases over the course of weeks or
occasionally months. In veterinary patients, the most impor-
tant provision to allow healing during this time is prevention
effects
Percent 60 of self-trauma of the irradiated site. Pain management plays
an important role and should be addressed. Pain management
for cancer patients is discussed in Chapter 16A of this text and
specific protocols have been published. Additional treatment
70
Large dose is based on common sense, supportive care, and the knowledge
per fraction that the signs will resolve with time.
Small dose Early delayed radiation effects have been recognized only in
5 per fraction neurologic tissues. Occurring between 2 weeks and 4 months
71
after treatment, they may take several forms. Somnolence may
72
Dose develop in patients receiving whole brain irradiation. Early
• Fig. 13.1 Radiotherapy delivered in small fractions (solid lines) can pro- delayed effects may simulate tumor recurrence or may cause
duce a higher probability of tumor control with the small level of late effects neurologic signs not previously associated with the tumor, and
as radiotherapy delivered in large fractions (broken lines). so careful imaging evaluation is necessary. Early delayed effects
may be due to demyelination or from cerebral edema–associated
(3) a reduction in the number of tumor cells that normally die cytokine release with tumor cell death. Early delayed effects will
(cell loss factor), or (4) an increase in the number of tumor stem generally respond to corticosteroid administration and support-
cells. Regardless of the cause, when treatment lasts longer than ive care. 71
4 weeks, repopulation may affect the outcome unless total dose Late effects are mechanistically more complex than acute
is increased to account for this phenomenon. Repopulation may effects and involve more slowly proliferating tissues, such as bone,
have a greater adverse effect on rapidly dividing tumors than on lung, heart, kidneys, and nervous system. The dose of radiation
slowly dividing tumors. administered to the patient is limited by the tolerance of these
Repopulation of rapidly proliferating (also known as acutely normal tissue structures in the field. Late reactions can be difficult
responding) normal tissues is also affected by time. The same to treat; it is the radiation oncologist’s obligation to minimize the
total dose of radiation administered over a short period results incidence of late effects with appropriate dose prescriptions and
in somewhat more severe acute effects than if administered over careful radiation planning and treatment. When late effects occur,
a longer course. 3,64–66 Nonproliferating (late responding) normal they may be quite severe, resulting in fibrosis, necrosis, loss of
73
tissues are not significantly affected by the length of time over function, and even death. Late effects occur from the loss of
which therapy is administered; 33,64–65 they are more affected by normal tissue stem cells with concurrent radiation-induced vas-
dose per fraction and total dose. 3,33 Additionally, fractions should cular changes and inflammation. These changes are multifacto-
be separated by at least 6 hours to allow repair of DNA damage rial, but the cytokine transforming growth factor beta (TGFβ)
to normal tissues. Cells of the brain and spinal cord may require is believed to play a critical role in radiation fibrosis. Strategies
66
74
additional time for complete repair. 66 attempted in human radiation oncology to mitigate late radiation
The total dose administered to a patient should have a low effects include the use of antioxidants and free radical scavengers
probability for causing significant late normal tissue reactions in (e.g., superoxide dismutase, vitamin E, thiol radioprotectors), vas-
the region of therapy; however, the response of tissues also depends cular directed therapies (e.g., clopidogrel, statins, pentoxifylline),
on the fraction size. For example, 48 Gy administered in 4 Gy antiinflammatory agents (corticosteroids), inhibitors of the renin-
fractions has a higher probability of causing late effects than 48 angiotensin system (e.g., ACE inhibitors), and stem cell thera-
Gy administered in 3 Gy fractions (Fig. 13.1). The probability of pies. Consequential late effects, the result of extensive damage to
73
tumor control is minimally affected because rapidly proliferating stem cells of acutely responding tissues such as colon, are indistin-
tissues, including tumors, are not as sensitive to the change in dose guishable clinically and histologically from late effects and should
per fraction. The benefits of protocols that use small doses per be managed in a similar fashion. 75
fraction are clear: they allow a higher total dose to be administered An unusual late effect associated with RT is the occurrence
without increasing the probability of damage to late-responding of radiation-associated secondary tumors. Ionizing radiation is a
normal tissues. Conversely, extending overall treatment time may complete carcinogen, capable of initiating, promoting, and pro-
allow for greater accelerated repopulation. 3,62,67–68 gressing cellular changes that lead to cancer. Therefore it is pos-
sible to see radiation-induced neoplasia develop in an RT field. It
Radiation Effects to Normal Tissues appears that radiation with high LET such as neutrons result in
carcinogenesis at a higher frequency than the megavoltage pho-
76
Reactions from RT are classified as acute, late, consequential, tons typically used in veterinary RT. Age influences the risk of
and early delayed. Acute effects occur during or shortly after radiation carcinogenesis because younger patients have the poten-
RT. Acute effects involve rapidly proliferating tissues, such as tial to live longer after radiation, and information from nuclear
the oral mucosa, intestinal epithelium, and epithelial structures accidents suggest that they are more likely to develop secondary
of the eyes and skin. Concurrent chemotherapy can exacer- tumors. 76,77 Certain tissues such as the thyroid gland are also more
78
69
bate acute radiation effects. Although the severity of acute prone to development of radiation-induced tumors. Secondary
effects may vary between patients, these effects generally are tumors have been reported in dogs in both clinical and research
self-limiting and recovery is rapid; however, acute effects can settings. 79,80