TREATMENT AND PROGNOSIS IN DOGS
Therapeutic options for dogs with nasal tumors are directed at local disease control. Given the restrictive anatomy of the
nasal cavity and associated sinuses as well as the proximity to delicate tissues like the eyes and brain, complete surgical
resection of nasal tumors is frequently difficult. Aggressive cytoreductive surgery also causes a high rate of morbidity with
no significant improvement in survival times compared with dogs treated only with palliative medications.5,11,13,32,33 As such, surgery is not considered a first-line treatment option, and the standard of care is radiation therapy alone or
a multimodality strategy combining radiation therapy with surgery or chemotherapy.
New advances in radiation delivery techniques that maximally spare normal tissue, such as intensity-modulated radiation therapy
(IMRT),34 helical tomography,35 and proton therapy,36
are also being evaluated for improving treatment outcomes in dogs with nasal tumors. Despite advances in therapeutic strategies,
anywhere from 63% to 100% of dogs treated with definitive radiation therapy protocols will experience local disease recurrence.37-42
The delivery of ionizing radiation with both orthovoltage or megavoltage therapy machines has been used for curative intent
and palliative therapy for nasal tumors. Radiation therapy has the advantage of treating the entire nasal cavity, including
bone, and its use has been associated with the greatest improvement in survival when compared with nonradiation treatment
options. A notable limitation of radiation, when used as the sole therapeutic modality, is the low cure rate achieved in the
treatment of large macroscopic tumor burdens. Despite radiation therapy's inability to cure most dogs, many patients treated
with radiation therapy enjoy relatively long durations of local disease control, improved clinical signs, and increased quality
of life scores.
Definitive treatment. Radiation therapy with curative intent has been previously described as a sole treatment option for nasal tumors in dogs.
Conventional protocols require the administration of small fractions (3 to 4.2 Gy) repeatedly (10 to 19 treatments) on a daily
or every other day basis for a total radiation dosage of 40 to 57 Gy.11,23,38,39 Three studies involving 82 dogs with nasal tumors that were treated with cobalt-60 radiation therapy alone reported median
survival times ranging from 12 to 19.7 months.37,38,43 In these three studies, no significant differences in survival times were identified in dogs with either carcinomas or sarcomas.
Interestingly, in a smaller pilot study, histopathologic subtype did appear to influence response to therapy. In this small
descriptive study, six dogs with nonkeratinizing squamous cell carcinoma of the nasal cavity treated with cobalt-60 radiation
therapy achieved only a median survival time of 165 days, suggesting that squamous cell carcinoma (Figure 4) may be a histopathologic subtype of nasal carcinoma that does not respond as well to radiation therapy.44
Figure 4. A nasal squamous cell carcinoma involving the rostral aspect of the left nasal cavity in a golden retriever. Note
the large area of ulcerative tumor growth.
Definitive treatment side effects. Ionizing radiation exerts its therapeutic effects through the direct and indirect breakage of cellular DNA. Thus, tumor cells
exposed to ionizing radiation will undergo programmed cell death as a consequence of irreparable DNA damage. This net effect
of cell death translates clinically into tumor mass shrinkage. However, damage done to cellular DNA by ionizing radiation
is not specific for tumor cells but will affect all cells within the field of radiation, including normal stromal cells associated
with the nasal cavity. As such, therapy with ionizing radiation is often associated with adverse effects to surrounding normal
tissues, which may be categorized as either acute or late effect radiation toxicities. Acute effects develop in tissues with
rapidly dividing cells such as basal epithelial cells, and these radiation side effects are generally self-limiting. Tissues
most commonly affected with acute effects include skin (desquamation), eyes (keratoconjunctivitis and blepharitis), and mucosal
surfaces (mucositis). Acute radiation effects develop during the first three or four weeks of therapy and typically resolve
within two or three weeks after treatment completion (Figures 5A & 5B).
Figure 5A. In a mixed-breed dog receiving definitive radiation therapy for nasal carcinoma, painful acute radiation side effects
can be observed involving the skin surrounding the eye and muzzle. (Image courtesy of Louis-Philippe de Lorimier, DVM, DACVIM
Although transient in nature, the management of acute effects is important and should include pain relief with nonsteroidal
anti-inflammatory agents or opioids. Oral antibiotics and artificial tears may also be necessary for supportive care until
the acute effects resolve completely. Late side effects of radiation therapy affect tissues with slower or minimal replicative
capacity including bone, blood vessels, and neuronal tissue. Late side effects of radiation are dose-limiting and dictate
maximum tolerated dosages of ionizing radiation deliverable to normal tissues within the treatment field. The onset of late
radiation side effects occurs six months or longer after the completion of radiation therapy, and associated damage to normal
tissues can be irreversible and associated with significant morbidity (Figure 6). In some cases, additional diagnostic testing may be necessary to differentiate between late radiation effects and tumor
Figure 5B. Several months after the completion of definitive radiation therapy, the damage from acute radiation toxicity has
healed, leaving regions of alopecia and hyperpigmentation. The right eye globe was included in the radiation field, and the
dog did go on to develop mild cornea edema. (Image courtesy of Louis-Philippe de Lorimier, DVM, DACVIM [oncology].)
Given the potential for normal tissue damage during radiation therapy, recent technological advances have focused on increasing
conformal targeting to minimize the volume of normal tissue exposed to the ionizing effects of radiation, with subsequent
reductions in early and late radiation toxicity. Two technologies that allow for conformal therapy include stereotactic radiosurgery
and IMRT. Two studies evaluating IMRT in dogs with nasal tumors have been reported. In the first study, IMRT was evaluated
in 12 dogs with nasal tumors with the intent to document IMRT's therapeutic effectiveness as well as to characterize the frequency
and severity of side effects.34 In these 12 dogs, the use of IMRT provided a median survival time of 14.9 months, with a low incidence of late effects.34 In a second larger study, IMRT was used to treat 31 dogs with sinonasal tumors with the intent of demonstrating an ocular-sparing
effect in conjunction with anticancer activities.45 In this study, IMRT exerted similar anticancer effects as conventional two-dimensional radiation therapy (with survival
times of 411 days vs. 420 days, respectively) but dramatically reduced the incidence and severity of early and late effects
to the eyes.45 These two early IMRT studies indicate that this radiation delivery technique provides therapeutic effects equivalent to
conventional two-dimensional radiation therapy but, more important, reduces the incidence and severity of radiation toxicity
to surrounding normal tissues.
Figure 6. After treatment with large fraction palliative therapy, a dachshund developed unacceptable late radiation side effects
manifested as osteonecrosis of the maxillary cavity. The open maxillary cavity with necrotic bone is being irrigated with
a stream of sterile saline solution. It is probable that there is local tumor recurrence (mass ventral to the eye), but it
was not confirmed in this case. The prognosis for the patient was very poor given that the late radiation effects were irreversible.
Radiation therapy with surgery. Some debate exists over combining radiation therapy with surgical resection for the management of canine nasal tumors. Most
studies do not demonstrate any added benefit when surgery is combined with radiation therapy for the localized management
of nasal tumors. In a recent analysis of 139 dogs with nasal tumors treated with radiation alone or radiation with cytoreductive
surgery, median survival times were not significantly improved by the addition of cytoreductive surgery, which is consistent
with many previous studies that also suggest that survival time remains unchanged with the addition of surgery to radiation
therapy.4,7,23,24,41,46 Collectively, these studies indicate that surgical cytoreduction before the delivery of radiation is not beneficial for
extending survival times.