Nasal tumors in dogs and cats (Proceedings)

Nasal and paranasal sinus tumors represent only 1-2% of all tumors but 60-80% of all canine respiratory tract tumors, and are even less frequent in cats. Nasal tumors occur most commonly in the nasal cavity with secondary extension into the frontal and other paranasal sinuses. Nasal tumors are primarily locally invasive and infrequently metastasize. The rate of metastasis at presentation in dogs and cats has ranged from 0-12.5%. There is no consistent sex predilection.

Dolichocephalic breeds have a higher risk while brachycephalic dogs have a lower risk of developing sinonasal cancer. Risk of nasal cancer appears to correlate with the amount of surface area in the nasal passages and the efficiency of the filtering capability an may be associated with environmental toxins. In cats there is some indication that chronic rhinitis/sinusitis may be an initiating factor for the subsequent development of nasal neoplasia. Nasal lymphoma has been reported in FeLV positive as well as FeLV negative cats.

The most common clinical signs are decreased airflow through the affected nasal passage, epistaxis and sneezing. Other signs include reverse sneezing, stertorous breathing, serous, mucoid or mucopurulent nasal discharge, dyspnea, and facial deformity or swelling. Ocular signs include ocular discharge, exophthalmia, blindness, and it may be possible to detect decreased retropulsion of the eye. Neurologic signs frequently occur only in the advanced disease state, but a subset of dogs and cats present initially for neurologic signs.

Clinical staging

Initial evaluation should include complete blood count, biochemical profile, urinalysis, regional lymph node aspiration cytology, three view thoracic radiographs, nasal biopsy, and imaging of the nasal cavity (radiographs, CT, and/or MRI). A coagulation profile is indicated prior to any nasal biopsy procedures or to rule out coagulopathy as a cause of epistaxis. Three view thoracic radiographs are recommended to rule out pulmonary metastasis, although thoracic metastasis is uncommon. Diagnosis can be made via cytology, nasal flush, traumatic core biopsy, and rhinoscopic biopsy. Cytology can be diagnostic but biopsy is recommended to obtain a definitive diagnosis. Radiographic examination of the nasal cavity can be helpful in advanced cases but changes may be minimal in early cases. CT or MRI imaging is more sensitive and has become the standard of care especially in situations where radiation therapy is to be utilized as part of treatment.

Histopathology

The most common epithelial tumors in dogs are adenocarcinomas, undifferentiated carcinomas and squamous cell carcinoma. Other epithelial tumors include transitional carcinoma, neuroendocrine tumors, and esthesioneuroblastoma. Chondrosarcoma and osteosarcoma are the most common mesenchymal tumors. Round cell tumors reported to involve the nasal cavity include lymphoma, transmissible venereal tumor and mast cell tumor. The most common tumors in cats are lymphoma and carcinoma (adenocarcinoma and undifferentiated carcinoma).

Treatment options

If not treatment is performed, survival time is limited. A recent study of 139 cases of nasal carcinoma not treated with radiotherapy, surgery, chemotherapy or immunotherapy, indicated a median survival time of 95 days (range 7-114 days). The prognosis was worse for dogs with epistaxis. In several studies, the majority of nasal carcinomas express COX-2 which is therefore a target for COX-2 inhibitors and treatment with a COX-s2 inhibitor should be considered although survival data is lacking.

Surgery alone is ineffective in the treatment of nasal cavity tumors resulting in survival times comparable to that observed in untreated dogs. The mean survival time for 41 dogs undergoing surgery alone was 4 months with a range of <1 month to 11.5 months. Surgery may be helpful in providing palliation if excessive bleeding occurs but this benefit is short lived. Also carotid artery ligation may help slow bleeding

Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy were retrospectively reviewed by. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Survival times were shorter in dogs that had partial or no resolution of clinical signs. Another earlier hypofractionated protocol involving four once-weekly fractions of 8-9 Gy to a total of 32-36 Gy indicated a median survival time of 278 days.

Radiation alone or after cytoreductive surgery has been the standard of care for treating nasal tumors. Cytoreductive surgery has been recommended prior to orthovoltage radiation due to lack of penetration of low energy orthovoltage radiation. The reported median survival times for dogs treated with orthovoltage radiation is 16.5-23 months. The median survival with cobalt irradiation for 27 dogs was 12.8 months, with a 1-year survival rate of 59% and 2-year survival rate of 22%. Comparable results were obtained in a study of 77 dogs treated with cobalt 60 teletherapy with a mean survival of 21.7 months and median survival of 12.6 months, 1-year survival rate of 60.3%, and 2-year survival rate of 25.1%. Failure in dogs with nasal tumors after radiation is usually due to local recurrence as opposed to metastasis. Very similar results have been seen with current radiation protocols utilizing linear accelerator based treatment. Recently strategies have been developed utilizing Intensity Modulated Radiation Therapy (IMRT) which offers the promise of increased dose to tumor relative to normal tissues but results have not demonstrated large outcome differences

Surgery alone in four cats with nasal adenocarcinoma or undifferentiated carcinoma resulted in a mean survival time of 2.5 weeks. In one report the interval between surgery and euthanasia ranged from 2-8 months. There are fewer reports on irradiation of feline nasal tumors. The median and mean overall survival time (n = 16 cats) in one study was 11.5 and 14.8 months respectively, with a 1- and 2-year overall survival rate of 44.3% and 16.7%. Evans reported a median survival (n = 9 cats) of 20.8 months with a 66.7% 1-year, 44% 2-year, and 33% 3-year survival rate. Straw reported median survival of 13 months for 6 cats treated with megavoltage radiation alone.

Nasal lymphoma cats can do quite well with 75% achieving CR. MST of 358 days with COP (Cyclophosphamide, Oncovin, Prednisolone) protocol was reported, although a bigger study reported a range of 14-541 days. A recent study of 19 cats given radiotherapy and chemotherapy showed a median survival of 955 days. Cats with nasal lymphoma can have long-term control with local irradiation alone although a subset fail due to systemic disease. FeLV+ cats may have a greater likelihood of failure due to systemic involvement and as such chemotherapy should be included in any radiation protocol to maximize efficacy.

Surgery following radiation therapy has recently been evaluated and has been shown to significantly improved survival time. Two- and 3-year survival rates were 44% and 24%, respectively for dogs in the radiotherapy group and 69% and 58%, respectively for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). This approach may prove to be the standard of care and should be considered if feasible.

Cisplatin chemotherapy in 11 dogs with nasal adenocarcinoma resulted in clinical improvement in all dogs with two complete responses and one partial response for an overall response rate of 27%. The median survival time for 13 dogs treated with a combination of external beam radiation therapy and slow release cisplatin was 580 days. Additional chemotherapy protocols have been described including an alternating carboplatin/ doxorubicin protocol in conjunction with piroxicam 4/8 dogs experienced complete responses for extended periods of time.

Prognostic factors.

The majority of studies have shown that classic WHO staging in dogs and cats does not have prognostic significance. A new staging system developed by Theon was shown to have prognostic significance for survival and showed that dogs with disease outside of the nasal have a poorer prognosis. Tumor histology has been shown to have prognostic significance with sarcomas (primarily chondrosarcomas) having a better prognosis than carcinomas. A more recent study did show prognostic significance with advanced disease

Selected references

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