Respiratory Neoplasia: Anything New?
World Small Animal Veterinary Association World Congress Proceedings, 2015
Brendan Corcoran1, MVB, DipPharm, PhD, MRCVS
1Professor, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Scotland, UK

The major recent advances in respiratory neoplasia have been the increased use and availability of radiation therapy for the management of nasal cancer. For pulmonary neoplasia there has been some advances in the use of chemotherapy, and with greater us of computed tomography, increased the capacity to determine the extent of cancer. It is still the case that surgical removal of large lobar tumours is beneficial even if there is evidence of metastatic spread. Tumours of the major conducting airways of cats and dogs are still very rare.

Nasal Neoplasia

Nasal tumours are typically malignant, occurring in older, medium to large size dogs, are locally aggressive and destructive and show limited metastatic tendency. The most common tumours are carcinoma, including adenocarcinoma, and sarcoma (fibrosarcoma, chondrosarcoma and osteosarcoma). In cats lymphomas are the most common followed by epithelial tumours. Nasal tumours show clinical signs typical of nasal disease with nasal discharge which is usually unilateral, but can become bilateral. The discharge can be serous, mucoid, mucopurulent or blood tinged. Overt epistaxis might occur, and the presence of blood is highly suspicious of neoplasia. Stertorous breathing, nasal deformity and nasal pain can also be present. Local pressure and extension can result in epiphora, exophthalmos and neurological signs.

Diagnosis

Usually this is achieved by using a combination of clinical history, presentation, imaging and histological evaluation. The latter is required for definitive diagnosis. CT is more accurate than plain radiography. Tissue sampling can be obtained by fine needle aspiration or biopsy. Flushing techniques tend to be ineffective. FNA of local lymph nodes is also advised and in suspect nasal lymphoma in the cat abdominal ultrasonography, bone marrow aspiration and FeLV/FIV testing might be needed to prove it is localised.

Therapy

Palliative therapy can be obtained with glucocorticosteroids and COX-inhibitors. Most nasal tumours when identified have already caused local destruction, and the extent of that destruction will affect the response to therapy. The greater the destruction the more likely therapy will be only palliative. Lymph node involvement is a poor sign as it suggest metastatic spread. However, detection of distant metastasis is rare, indicating that therapy is always warranted in nasal neoplasia.

Radiotherapy (RT) is now accepted as the definitive treatment for nasal neoplasia, and has replaced surgery as the advised procedure. There have been major advances such that a range of sophisticated RT protocols are available and with close linkage to imaging technologies improvements in efficacy and safety.

Without treatment of nasal cancer survival can be as low as 1–3 months, but will vary with tumour type. With RT alone, median survival can be up to 19 months and greater than 36 months. Radiotherapy can also be used when palliation is the only option, and tends to give survival times of 3 to 9 months. Nasal lymphoma in cats is particularly sensitive to RT when used in conjunction with chemotherapy. Chemotherapy can give resolution for up to 9 months and an example protocol is intravenous carboplatin and doxorubicin weekly for three weeks and daily oral piroxicam. The benefit of chemotherapy in non-lymphoma nasal tumours is unclear. All these treatments have potential side effects, with the side-effects of radiation therapy often due to damage to local adjacent tissue and structures; oral mucositis, conjunctivitis, rhinitis, keratoconjunctivitis sicca, progressive vision loss in eye close to the radiotherapy zone. Re-irradiation can also be considered in dogs with reappearance of signs and can give respectable survival in some cases. If the tumour is sinonasal this can prove more difficult to treat with RT due to the proximity of important structures including the eye and brain.

Pulmonary Neoplasia

Lung parenchymal tumours can be either primary or metastatic, with the latter more common since the lung is the main site of metastases for malignant tumours. Primary lung tumours can also metastasise locally to other lung sites. Single primary lung tumours that are detected incidentally, have the best prognosis, while metastatic lung disease has a very grave prognosis and apart from palliative therapy, is untreatable.

Lung neoplasia is typically found in middle to old-aged dogs and results in clinical signs typical of respiratory disease. Coughing is common with primary neoplasia as it is invariably due to bronchial compression. Dyspnoea, exercise intolerance and para-neoplastic signs such as cachexia and hypertrophic pulmonary osteopathy, are poor prognostic signs. The progression of primary tumour growth and spread is not known, but is probably quite slow in the early stage of disease and becomes more rapid in the later stages. This suggests that early detection of disease, particularly solitary masses, and immediate surgical intervention, would greatly improve outcome.

The most common primary tumours are carcinomas, with adenocarcinoma and bronchoalveolar carcinoma making up the majority. Other primary tumours reported include anaplastic carcinoma and histiocytic sarcoma (although the more typical disseminated nature of this form of cancer suggests it is not primary pulmonary). Examples of common secondary tumours are osteosarcoma, mammary carcinoma, melanoma, lymphoma, hemangiosarcoma and anal sac adenocarcinoma.

Diagnosis

Diagnosis in general practice is based on identification of classic radiographic changes (three views) in the right age of dog. Typically, primary tumours are single lung lobe masses and so are very radiodense and well delineated. For histiocytic sarcomas common radiographic features include whole lobe involvement (large tumour), right middle or left cranial lobe location and with an internal air-bronchogram. They can involve multiple lobes (more advanced disease), and in rare instance adenocarcinomas can present as a diffuse nodular-interstitial lung pattern. Metastatic lung neoplasia typically gives well delineated multiple nodular densities (cannonball lung), less well defined multiple masses, or diffuse nodular-interstitial density. The staging of disease also involves imaging assessment of lymph nodes, which if present gives a poor to grave prognosis. Disease extent, and therefore, prognosis is greatly improved with use of CT. Positron emission tomography linked to CT (PET/CT) allows functional assessment of pulmonary neoplasia and has widely impacted on management of neoplasia in human patients, and is becoming more available in veterinary specialist centres. Definitive diagnosis, however, depends on histological confirmation, but failure to do so should not prevent an attempt at surgical removal of well delineated, localised mass lesions. Samples can be obtained by direct fine needle aspirate of the lesion.

Therapy

Resection of the affected lung lobe, with associated lymph nodes if possible, is the preferred treatment for primary lung neoplasia and prognosis is greatly improved if there is no lymph node involvement and the tumour is less than 5 cm (often only confirmed at surgery). In cats the prognosis is good with well-differentiated tumours but poor if there is lung-digit syndrome. In all cases at the time of diagnosis there is a presumption that metastatic spread has already occurred, even if at the time of surgery metastases are not visible. Survival can be up to 24 months, but there is no data on how long survival might be for asymptomatic incidental primary tumours, and therefore whether or not surgery improves survival in such cases. In clinically affected dogs survival without treatment tends to be weeks rather than months. In those dogs that have negative prognostic indicators (e.g., involvement of several lobes and/or lymph node, pleural effusion, hilar localisation) surgical resection might only result in a maximum of 6–8 month survival. For histiocytic sarcomas survival is very poor with a median of 3 months.

Chemotherapy has limited value in pulmonary neoplasia, but can be considered for palliative treatment of extensive primary lung tumours where resection has not been complete, and for metastatic neoplasia. Reported protocols include; cisplatin, carboplatin and vinorelbine for primary carcinomas, the CHOP protocol for lymphoma and cisplatin/carboplatin for osteosarcoma. Radiation therapy has not become widely used for pulmonary tumours, but machines with image guided-IMRT are used widely in treatment of lung cancer in humans, and it is expected that these techniques will eventually be available for veterinary patients.

References

1.  Barrett LE, Pollard RE, Zwingenberger A, Zierenberg-Ripoll A, Skorupski KA. Radiographic characterization of primary lung tumors in 74 dogs. Vet Radiol Ultrasound. 2014;55:480–487.

2.  Harris BJ, Lourenço BN, Dobson JM, Herrtage ME. Diagnostic accuracy of three biopsy techniques in 117 dogs with intranasal neoplasia. J Small Anim Pract. 2014;55:219–224.

3.  Fujiwara-Igarashi A, Fujimori T, Oka M, Nishimura Y, Hamamoto Y, Kazato Y, Sawada H, Yayoshi N, Hasegawa D, Fujita M. Evaluation of outcomes and radiation complications in 65 cats with nasal tumours treated with palliative hypo-fractionated radiotherapy. Vet J. 2014;202:455–461.

4.  Mayhew PD, Hunt GB, Steffey MA, Culp WTN, Mayhew KN, Fuller M, Johnson LR, Pascoe PJ. Evaluation of short-term outcome after lung lobectomy for resection of primary lung tumors via video-assisted thoracoscopic surgery or open thoracotomy in medium- to large-breed dogs. J Am Vet Med Assoc. 2013;243:681–688.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Brendan Corcoran, MVB, DipPharm, PhD, MRCVS
Royal (Dick) School of Veterinary Studies
The University of Edinburgh
Roslin, Scotland, UK


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