Page 523 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 24 Tumors of the Respiratory System 501

an intensity modulated radiation beam to achieve extreme preci- Although true statistical comparisons between studies are not pos-
sion. 128 Initial SRT experiences in dogs with nasal tumors have sible because of inconsistencies in methodology, the best clinical
151–153
Published reports include radiation prescrip-
been variable.
outcomes in terms of survival (approximately 300–500 days) are
VetBooks.ir tions with median doses ranging from 24 to 36 Gy delivered in reported in three studies in which RT planning was performed
three fractions (3 daily or every-other-day fractions of 10 Gy, or 3
using CT and 3D-conformal computerized treatment plan-
daily treatments of 8–12 Gy) 152,153 or as a single fraction of up to ning software in most dogs. 109,133,158 Modernized RT planning
33 Gy. 151 In all of these studies, SRT improved clinical signs asso- in canine nasal tumor patients treated palliatively may result in
ciated with sinonasal tumors. MST varied, however, ranging from more favorable clinical outcomes than for previously reported, less
8.5 months to 19.5 months. Tumor control is dose-dependent, sophisticated approaches. 109,157,158 When lower doses per frac-
and thus will be contingent on the dose prescription, number of tion are used, such as the five daily treatments of 4 Gy protocol
fractions, accuracy of target delineation in the treatment plan- described by Tan-Coleman, the radiation treatment course can be
ning process, dose heterogeneity across the tumor, and accuracy repeated upon return of clinical signs to prolong palliation. 157 The
of treatment delivery. Variation between studies in any of the fac- use of a nonsteroidal antiinflammatory drug can also help improve
tors can dramatically affect clinical outcome. Interestingly, tumor overall quality of life. 136
stage was not prognostic in any of these SRT studies, 151–153 which A number of reports suggest that some dogs with recurrent
may reflect the ability of modern conformal RT techniques to nasal tumors can experience a second clinical remission after reir-
deliver adequate radiation doses to regions of tumor that abut radiation. 157,159,160 One study evaluated a selected cohort of nine
critical structures such as the brain. Acute effects associated with dogs in which the median time to tumor progression after a first
SRT at the doses delivered are reportedly rare and mild, although definitive course of RT was 513 days. The first course of radiation
it is possible they were underreported. 151–153 Given the high dose delivered a median of 50 Gy in a median of 18 fractions. The
per fraction used with SRT, the risk of late effects is higher than median total dose used in the second protocol was 36 Gy, deliv-
for conventionally fractionated protocols. With thoughtful treat- ered in approximately 2-Gy fractions. The overall MST for this
ment planning and use of normal tissue dose constraints during small, selection-biased cohort of dogs was 927 days (95% confi-
the treatment planning process, late effects can be minimized. 153 dence interval [CI] 423 days to 1767 days). All dogs developed
Severe late complications can include oronasal fistula formation, one or more late effects involving the skin, eyes, and nasal cavity.
seizures, ocular changes, skin necrosis, and osteonecrosis. 151–153 Late effects in seven of the nine dogs were considered mild and
Late effects are reported in 3% to 40% of dogs and depend on did not affect quality of life. Severe late effects were reported in
the degree of dose conformality achieved during the treatment two dogs, and both had sudden blindness that led to euthanasia.
process and the dose delivered to normal tissues. 151–153 The most A second study reports a MST of 453 days in 37 dogs that were
favorable outcome reported to date both in terms of tumor con- reirradiated after a coarsely fractionated radiation protocol. 159 The
trol and toxicity is reported by Gieger et al. who prescribed three median dose for the first course of RT was 24 Gy (median dose
daily fractions of 10 Gy planned with well-defined and standard- per fraction, 7 Gy), and then 20 Gy for the second course (median
ized contouring practices and normal tissue constraints. 153 In dose per fraction, 8 Gy). The second course was initiated a median
that study of 29 dogs, three developed fistulas within the radia- of 150 days after the first. All dogs responded clinically after the
tion field 4 to 12 months after RT, two of which may have been first course for a median of 114 days, and 70% responded after the
related to tumor response or progression as opposed to radiation. second course for a median of 80 days. Acute toxicities were gen-
Two dogs developed fungal rhinitis 1 year after RT. No infor- erally mild and included the skin, oral mucosa, and eye, although
mation about ocular toxicity was provided. The MST was 586 normal tissue doses are not described. Based on these reports, reir-
days. Despite the multiple apparent advantages of SRT, the chal- radiation for recurrent nasal tumors can result in improvement
lenges associated with optimal use of this technology must be in clinical signs and potentially extend survival time. In a third
considered and treatment plan evaluation must be optimized. study of dogs with sinonasal sarcoma, eight dogs that underwent
Controlled clinical trials that rigorously examine normal tissue reirradiation had a longer MST (654 days) than those that had
effects and tumor responses are still needed to validate use of SRT a single course of RT (356 days). Further work is needed to
28
over standardly fractionated conventional RT or IMRT/IGRT in refine time-dose prescriptions to minimize radiation-induced late
veterinary medicine. effects. 159,161 Conformal techniques such as IMRT could play a
In contrast to curative-intent RT protocols, treatment sched- role in this setting to limit morbidity. 161
ules that are less intensive can be used to palliate tumor-related Chemotherapy is used rarely as a sole therapy for canine sino-
clinical signs. The goal of palliative RT is to improve quality of life nasal tumors. Treatment with cisplatin alone has been shown to
without aiming to maximize tumor sterilization. Palliative pro- benefit some dogs. 162 A clinical response rate of 27%, including
tocols involve coarsely fractionated treatments (5–9 Gy per frac- one radiographically-confirmed complete remission, was reported
tion) delivered weekly or biweekly, or daily treatments (4 Gy) for 5 in a small series of 11 dogs. 162 All of the dogs experienced allevia-
days, or daily treatments (3 Gy) for 10 days. 69,109,110,136,154–158 The tion of clinical signs, and the MST was 5 months. Another report
result of this approach is temporary improvement of clinical signs evaluated a combination chemotherapy protocol of doxorubicin,
in 66% to 100% of dogs and limited morbidity associated with carboplatin, and oral piroxicam in eight dogs with advanced nasal
acute side effects. 109,136,154–158 The reported median duration of tumors. 163 A clinical response rate of 75% was observed, includ-
control of clinical signs ranges from 120 to 308 days. 109,155,157,158 ing 4 CRs confirmed by CT imaging. All dogs experienced reso-
Acute toxicities affecting the oral mucosa and skin are generally lution of clinical signs, and the protocol was well tolerated. The
mild and short-lived. 109,154–158 Acute and chronic ocular toxici- MST in these eight dogs was 210 days (range 150–960 days).
ties can develop if the eye is not spared. 155,157,158 Reported MSTs These preliminary results are favorable, but the case number is
range from 146 days to 512 days. 69,109,154–158 Tumor stage (stage 1) small, and more dogs need to be treated in this manner to confirm
and duration of clinical signs (>90 days) have been correlated these findings. Toceranib phosphate, a TKI, was associated with a
with longer survival in cases receiving this type of radiation. 109,155 clinical benefit in five of seven dogs (71%) with nasal carcinoma,