Canine Nasal Carcinoma: Summary of Diagnosis and Conventional Treatment Options

This exclusive article is part of the MettaPets Veterinary Professional Blog Series

This article is the intellectual property of Dr. Erin Bannink, September 2021.

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Western Biomedicine Perspective

Carcinomas are the most commonly diagnosed canine intranasal tumor, and will be the focus of this article. Various sarcomas, including fibrosarcoma, chondrosarcoma, and osteosarcoma, comprise the remaining 1/3 of cases, with lymphosarcoma diagnosed rarely in dogs compared to cats. The most common sites of metastasis for nasal carcinoma are the regional lymph nodes and lungs, although the presence of metastasis at the time of diagnosis is uncommon. Clinical signs attributable to the primary tumor are the most common cause of death, even in cases where metastasis has occurred. Although advancements in conventional therapy, including radiation therapy, are helpful in tumor control and management of quality of life issues related to the primary tumor, cure is not expected even with aggressive therapy and most patients are eventually lost to clinical signs related to cancer.

Molecular Aspects

Canine epithelial nasal tumors have been shown to express vascular endothelial growth factor (VEGF) and epithelial growth factor receptor (EGFR). VEGFR was a more consistent finding, with 92% of tumors positive for VEGFR expression compared to 55% for EGFR.9 Inhibition of VEGF and EGFR have improved radiation responses in human clinical trials and may be an effective method to improve disease control in canine patients. COX-2 expression has been demonstrated in 70-80% of canine nasal carcinomas.10,11

Treatment and Survival

Presence of epistaxis is a major factor in survival for patients with untreated nasal tumors. Median survival time (MST) for dogs with untreated nasal tumors is about 3 months. Dogs with epistaxis have a significantly shorter MST of 3 months (n=108) compared to MST of 7.5 months (n=32) for those without epistaxis.1

A number of staging systems have been proposed for canine nasal tumors, but the prognostic significance is still questionable. The modified Adam’s system seems to correlate best with survival time after radiation therapy, particularly when considered along with histopathology.

Stage 4 disease, tumors associated with lysis of the cribriform plate, showed the shortest survival times (MST about 7 months). MST for stage 1 tumors, confined to the nasal passage, paranasal sinus or frontal sinus with no bone involvement beyond the turbinates, were associated with the longest survival times (MST about 2 years). Disease free interval (DFI) was impacted by histologic diagnosis, but not overall survival time. Carcinomas had a DFI of 4.4 months compared to 10.6 months for sarcomas.2

Complicating evaluation of true treatment efficacy are small study size for most published articles as well as challenges with evaluable endpoints for nasal tumors. Serial advanced imaging such as CT or MRI to assess tumor response are not routinely performed due to cost and need for anesthesia. Survival time is, therefore, often reported as the evaluable endpoint. However, decisions regarding timing of euthanasia are highly variable between pet owners. These limitations have contributed to the lack of a clearly defined optimal treatment approach for this disease.

Conventional Treatment Options

Treatment protocols including radiation therapy have resulted in the longest reported survival times. Full course megavoltage photon radiation therapy is the standard treatment and in a MST of approximately 1 year. Recent advances in radiation therapy and availability of /Intensity-Modulated Radiation Therapy (IMRT) and stereotactic radiation units in veterinary medicine have resulted in availability of radiation protocols associated with less side effects and improved quality of life, but not marked improvement in survival time.

IMRT was evaluated in nasal tumors. Complete resolution of clinical signs was observed in 67% of patients (n=8). Overall MST was 15 months. One- and two-year survival rates were 50% and 25% respectively.3 Acute side effects were minimal in the oral mucosa and the contralateral eye, which is an improvement over standard megavoltage radiation therapy.

Stereotactic radiation therapy (SRT) is a highly localized form of radiation which is administered in a few daily doses. Retrospective evaluation of 19 dogs treated with three consecutive daily doses (8-12 Grey each) showed a median survival time of 13 months. This survival was comparable to full course megavoltage radiation therapy but with significantly less acute side effects and fewer required treatments.

Palliative radiation therapy was evaluated in a population of 18 dogs using a protocol of five 4-Grey fractions. Complete resolution of clinical signs occurred in 78% of patients for a median response duration of 6 months. Six dogs underwent a second palliative course of radiation with a median response duration of an additional 4 months and overall MST of 10 months.5 Other studies have shown MSTs of 5 months6 and progression free survival (PFS) of 8.5 to 21 months depending on stage of disease.

Nasal externation following radiation therapy has been evaluated in a number of studies and, although the procedure appears to be well tolerated, survival times are not markedly improved over radiation therapy alone, with MST of 15 months.

The goal of standard doses of chemotherapy is to cause tumor regression and alleviate clinical signs. Chemotherapy is usually given every 3 weeks for 5-6 treatments. The addition of chemotherapy to radiation therapy has not resulted in improved survival times. There are limited reports on efficacy of chemotherapy alone as a palliative treatment for nasal carcinoma, however response rates between 25-75% have been reported. MST was 5-7 months in two studies, one evaluating Cisplatin (n=11) and the other a combination of carboplatin, doxorubicin and Piroxicam (n=8).

Palliation with metronomic chemotherapy or Palladia: Metronomic chemotherapy utilizes low doses of oral chemotherapy agents and other drugs for disease control. This treatment targets the process of new blood vessel formation (angiogenesis) initiated by the tumor tissue which is necessary for tumor masses to grow beyond a size of 2mm. Tumor regression is less likely with this approach compared to high dose chemotherapy, so it is best suited for patients who have minimal clinical signs in which disease stabilization is the goal.

Palladia (Toceranib) is a veterinary tyrosine kinase inhibitor which was originally developed to treat aggressive mast cell tumors. The primary mechanism of action is inhibition of KIT signaling, which is a key factor involved in mast cell tumor progression. Objective responses have been seen in various solid tumors, including nasal carcinomas, treated with Palladia. A preliminary evaluation for biological activity in solid tumors showed stable disease in 4/7 dogs with nasal carcinoma and a complete response in one dog.15 Targets for Palladia are various receptor tyrosine kinases including VEGFR, which is expressed in a majority of canine nasal carcinomas.

The additional of a COX-2 inhibitor to radiation therapy has been evaluated and did not result in improved survival over radiation alone, with MST of 11 months in the radiation treatment group and MST of 8 months in the radiation plus firocoxib group. However, improved quality of life as determined through owner quality of life questionnaires was improved in the patients receiving firocoxib therapy.

1. Rassnick KM, Goldkamp CE, Erb Hn, et al. Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003). J Am Vet Med Assoc 2006 Aug 1;229(3):401-6.

2. Adams WM, Kleiter MM, Thrall DE, et al. Prognostic significance of tumor histology and computed tomographic staging for radiation treatment response of canine nasal tumors. Vet Radiol Ultrasound 2009;50:330-335.

3. Hunley DW, Mauldin GN, Shiomitsu K, et al. Clinical outcome in dogs with nasal tumors treated with intensity-modulated radiation therapy. Can Vet 2010 Mar;51(3):293-300.

4. Glasser SA, Charney S, Dervisis NG et al. Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors. J Am Anim Hosp Assoc 2014 Mar-Apr;50(2):96-104.

5. Tan-Coleman B, Lyons J, Lewis C. et al. Prospective evaluation of a 5 x 4 Gy prescription of canine nasal tumors. Vet Radiol Ultrasound 2013 Jan-Feb;54(1):89-92.

6. Gieger T, Rassnick K, Siegel S, et al. Palliation of clinical signs in 48 dogs with nasal carcinomas treated with coarse-fraction radiation therapy. J Am Anim Hosp Assoc 2008 May-Jun;44(3):116-23.

7. Buchholz J, Hagen R, Leo C, et al. 3D conformational radiation therapy for palliative treatments of canine nasal tumors. Vet Radiol Ultrasound 2009 Nov-Dec;50(6):679-83.

8. Bowles K, DeSandre-Robinson D, Kubicek, et al. Outcome of definitive fractionated radiation followed by externation of the nasal cavity in dogs with sinonasal neoplasia: 16 cases. Vet Comp Oncol 2014 Sept 2 (Epub ahead of print).

9. Shiomitsu K, Johnson CL, Malarkey DE, et al. Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours. Vet Comp Oncol 2009 Jun;7(2):106-14.

10. Impellizeri JA, Esplin DG. Expression of cyclooxygenase-2 in canine nasal carcinomas. Vet J 2008 Jun;176(3):408-10.

11. Klieter M, Malarkey DE, Ruslander DE, et al. Expression of cyclooxygenase-2 in canine epithelial nasal tumors. Vet Radiol Ultrasound 2004 May-June;45(3):255-60.

12. Cancedda S, Sabattini S, Bettini G, et al. Combination of radiation therapy and firocoxib for the treatments of canine nasal carcinoma. Vet Radiol Ultrasound 2015 May;56(3):335-43.

13. Hahn KA, Knapp DW, Richardson RC et al. Clinical response of nasal adenocarcinoma to cisplatin chemotherapy in 11 dogs. J Am Vet Med Assoc 1992;200:355-357.

14. Langova V, Mutsaers AJ, Phillips B, et al. Treatment of 8 dogs with nasal tumors with alternative doses of doxorubicin and carboplatin in cinjunction with oral piroxicam. Aust Vet 2004;82:676-680.

15. London C, Mathie T, Stingle N, et al. Preliminary evidence for biological activity of toceranib phosphate (Palladia) in solid tumors. Vet Comp Oncol 2012 Sept;10(3):194-205.