Oncology and Veterinary Clinical Pathology, Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
Canine nasal tumors are one of the more common tumor types in dogs representing up to 1% of all cancers. The majority are carcinomas including adenocarcinomas, squamous cell carcinoma and undifferentiated carcinomas. The remaining include fibrosarcomas, chondrosarcoma and osteosarcoma, but occasionally lymphoma, mast cell tumors, malignant melanoma, hemangiosarcoma and other pathologies are diagnosed. They are characterized by local invasion with inflammatory infiltration consisting of neutrophils, macrophages and plasma cells and low metastatic rates with local lymph nodes and lungs being the most common metastatic sites.
Patients are most often >10 years of age and present with progressive signs of nasal disease such as unilateral nasal discharge, episodes of epistaxis and sneezing as well as deformity of the nasal bones. If there is invasion of the cribriform plate neurological signs may be part of the clinical presentation. Despite the addition of CT and MRI as imaging modalities for the nasal cavity, imaging alone is not enough for a positive diagnosis and imaging features cannot identify particular tumor pathologies.
Therefore, one of the major challenges is still to get an adequate tissue sample to allow a more precise diagnosis to guide the choice of therapy. Obtaining a biopsy often requires invasive measures and as bleeding can be a complication hemostasis testing such as thromboelastography (TEG) or a coagulation profile is often recommended.
The majority of research over the past 5–10 years has focused on advanced imaging techniques including PET-CT and their ability to discern specific nasal tumor pathologies as well as optimizing radiation therapy (RT) protocols through the use of IMRT (intensity modulated RT).
Standard of Care?
Diagnosis: Preferentially a tissue biopsy should be obtained for histopathology, but under some circumstances cytology samples may be accepted.
Clinical staging prior to initiation of therapy: A minimum database (MDB) consisting of a complete hemogram including blood smear evaluation, biochemistry, and urinalysis, nasal and thoracic imaging by either X-ray, but preferentially CT or MRI as these are superior to conventional radiography of the nasal cavity in delineating extent of tumor. A study has showed no advantage of MRI over CT and CT has the advantage of providing information on bone lysis, whereas others have shown no difference.
Therapy: Radiation therapy (RT) is the treatment of choice supported by several studies also in recent years. The expected survival at 1 year ranges from 43–68% and the 2-year survival ranges from 11–44%. Most RT protocols involve 10–18 treatments delivered in 3–4.2 Gy fractions.
Chemotherapy have shown inferior to radiation therapy, but may be considered when RT is not available or as rescue treatment after RT. Various chemotherapeutic protocols have been reported, including single agent cisplatin and multi agent doxorubicin, cisplatin and piroxicam. Recent studies have reported protocols utilizing mitoxantrone in combination with NSAIDS, and adjuvant therapy with local slow releasing carboplatin gel after cytoreduction.
Response evaluation criteria: restaging 6 and 12 weeks after RT including if possible a minimum database (MDB) consisting of a complete hemogram including blood smear evaluation, biochemistry, and urinalysis, nasal and thoracic imaging by preferentially CT.
Follow-up: Every month for one year and every three months thereafter: physical examination and CT q6 months. If suspicion of relapse confirmation by cytology or histopathology.
On the Horizon
The future diagnosis and management of canine nasal cavity tumors likely will include molecular diagnostic techniques, molecular imaging (PET-CT, PET-MRI and potentially also HyperPET) to guide IMRT as well as species specific immune therapeutic approaches.
1. Kuhlman GM, Taylor AR, et al. Use of a frameless computed tomography-guided stereotactic biopsy system for nasal biopsy in five dogs. J Am Vet Med Assoc. 2016;248(8):929–934.
2. Lux CN, Culp WTN, et al. Prospective comparison of tumor staging using computed tomography versus magnetic resonance imaging findings in dogs with nasal neoplasia: a pilot study. Vet Radiol Ultrasound. 2017;58(3):315–325.
3. Clausen MM, Hansen AE, et al. Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study. Radiat Oncol. 2013;8:262.
4. Clausen MM, Hansen AE, et al. Dose painting based on tumor uptake of CuATSM and FOG: a comparative study. Radiat Oncol. 2014;9:228.
5. Jafry Z, Gal A, et al. Proposed expansion margins for planning organ at risk volume for lenses during radiation therapy of the nasal cavity in dogs and cats. Vet Radiol Ultrasound. 2017;58(4):471–478.
6. Kubicek L, Milner R, et al. Outcomes and prognostic factors associated with canine sinonasal tumors treated with curative intent cone-based stereotactic radiosurgery (1999–2013). Vet Radiol Ultrasound. 2016;57(3):331–340. doi: 10.1111/vru.12349.Epub2016 Feb 15.
7. Bradshaw TJ, Bowen SR, et al. Molecular imaging biomarkers of resistance to radiation therapy for spontaneous nasal tumors in canines. Int J Radiat Oncol Biol Phys. 2015;91(4):787–795.
8. Bradshaw TJ, Fu R, et al. Predicting location of recurrence using FOG, FLT, and Cu-ATSM PET in canine sinonasal/tumors treated with radiotherapy. Phys Med Biol. 2015;60(13):5211–5214
9. Christensen NI, Forrest LJ, et al. Single institution variability in intensity modulated radiation target delineation for canine nasal neoplasia. Vet Radiol Ultrasound. 2016;57(6):639–645. doi: 10.1111/vru.12398. Epub 2016 Jul 28.
10. Domingo V, Balana B, et al. Canine sino-nasal tumours treated with mitoxantrone and NSAIDs: a retrospective study. ESVONC. Lyon 2017. Poster presentation.
11. Szendi E, Michalik L, et al. Slow release, gel based local chemotherapy for canine nasal tumors. ESVONC. Lyon 2017. Poster presentation.