The use of imaging is very important in the management of the majority of oncology patients. The two most important pieces of information that are required to plan the approach to a patient with cancer are the diagnosis and the extent of disease present in the patient. The former is best assessed with the use of biopsies, though some of the information can be achieved with the use of cytology. Imaging is important in evaluating the extent of disease. Biopsy techniques have been discussed in a previous session.
Radiography has been used for many years in the evaluation of veterinary patients and in many cases, with radiographs taken with care, they still are very useful, they are readily available and are relatively cheap to produce. They can be used for the evaluation of a patient for metastatic disease, especially in the thoracic cavity. Radiographs are useful in the evaluation of bone involvement in oral tumours and the limbs. Abdominal views can show marked lymphadenopathy, particularly in the sublumbar area, overall size of visceral organs and changes in texture, especially calcification. Secondary effects of cancers, including bowel obstruction and megaoesophagus, are often found with radiographs.
In the last 20 to 30 years, the use of ultrasonography has become much more widespread in the veterinary profession with a marked improvement in the quality of the images obtained. Ultrasonography is used widely as the primary tool for the evaluation of abdominal disease including primary and secondary cancers. This modality has a role in the thorax when there are fluid or masses present as well as in cases with cardiac involvement.
Both of these imaging modalities have limitations. All imaging methodology quality is reduced when poor techniques are used. Ultrasonography is dependent on operator experience including recognition of artefacts. For the foreseeable future they will remain important tools, but other imaging methods are becoming more available.
Nuclear scintigraphy has been used in veterinary medicine for years. In the oncology patient, its use has only slowly changed over the years. Its use has also remained primarily restricted to universities and a small number of larger private referral centres. Scintigraphy using technetium-99m is used in patients with bone cancers to assist in determining the extent of primary tumours and as a sensitive tool for screening for metastatic lesions. It is used in thyroid tumours in cats and dogs for the differentiation of benign and malignant disease and for planning radioiodine therapy.1 There has been limited use in veterinary oncology in the search for other cancers, especially some of the neuroendocrine tumours such as insulinoma.
The imaging tool that has become much more widely available is computed tomography (CT) scanning. For years in human oncology it has been used as a screen for metastatic disease in patients with malignant tumours. Due to a combination of a reduction in cost and improvements in technology that have reduced imaging times, it is now used more often for veterinary oncology patients. How it is best used and how the findings should influence patient management have not been determined fully.
In the thoracic cavity, CT is more sensitive than radiographs for the presence of metastatic lesions in the lungs and lymph nodes.2 On radiographs it can be difficult to identify mild to moderate lymphadenopathy both in the hilar area and anterior mediastinum. The sensitivity of detecting lung nodules using radiographs decreases rapidly in nodules less than 5 mm in diameter. Smaller nodules can be seen, but also can be missed. Utilising CT, nodules of 2 to 3 mm can be seen when they are present. For many years we have based our prognosis for highly malignant diseases such as appendicular osteosarcoma on thoracic radiographs. What is not clear, is the impact for a patient if nodules are present that can be detected on CT, but not radiographs. These should make a difference, but it has not been evaluated.
In the abdomen, ultrasound can be limited by gas shadowing and body conformation, especially deep-chested dogs. The technical difficulty of tracking the entire intestinal track from the gastric cardia to the rectum usually cannot be performed. There are cases where lesions are not seen on ultrasound that would impact the management of the patient. Abdominal CT is also being used more often. When post-contrast scans are utilised with careful consideration of the timing after administration of the iodinated agent, early metastatic lesions can be identified. The detail that can be seen of the anatomy can be very helpful.
To obtain a good-quality CT of the thorax and abdomen requires either heavy sedation or anaesthesia. The latter is preferable as this can allow breath holding that is important in removing movement artefact in the thorax and anterior abdomen. For many patients there is a significant increase in cost of performing screening using CT compared to abdominal ultrasonography and thoracic radiographs as well as the increased risk to the patient from the anaesthesia. These need to be weighed against the improved information and accuracy of the tests. There is also an additional benefit with the use of CT as there is improved screening of the bones and soft tissues surrounding the cavities. While not common, we find lesions in the bones and muscles that were not expected that would not have been found if screening had been undertaken with radiographs and ultrasound. There is not much increase in the time required for a CT, nor the costs, to screen the patient from nose to tail.
Magnetic resonance imaging (MRI) is becoming more available for veterinary patients, though the costs are higher. Evaluation of neurological disease has been the prime use of this modality, it can be very useful in evaluation of the soft tissues. This is the modality of choice for evaluation of a patient with a suspected central nervous system disease. It is used in the evaluation of some peripheral nerve diseases, particular nerve sheath tumours and lymphoma. It is not widely used in the evaluation of soft tissue tumours, especially sarcomas, but this is increasing. There is good delineation of the local extent of disease and which deeper tissue planes are involved. The ears and nose can also be evaluated with MR. Movement artefacts in the thorax and abdomen have limited its use.
All of the modalities listed above are used to primarily detect the physical extent of disease. After treatment, responses are gauged on changes in size of the disease. With standard therapies this has been an adequate measure of response. This is changing with the use of some of the newer treatment options.
Positron emission tomography (PET) is used commonly in people with cancer. The most frequently used scan utilises 18-fluorodeoxyglucose (FDG). This positron emitter is an analogue of glucose but it is not able to be metabolised at the same rate as glucose so persists in the cells. The amount is proportional to the metabolic activity of the cells. As cancer cells have a high metabolic demand, they are highlighted with this imaging tool. As with scintigraphy there is not good spatial and anatomical information available from these scans, now most units also incorporate a CT to allow a fused image of the metabolic activity from the PET and the anatomical detail from the CT.
PET/CT can be used for more than screening for cancer.3 There are some drawbacks as it is not specific and areas of inflammation will also be highlighted and this can be misleading. As the brain is very metabolically active, lesions might not be visible, though at times they are seen as areas of reduced activity. As well as 18-FDG, there are many other tracers available and being developed. They have tracers that relate to the proliferative activity in a tissue and hypoxia. Markers of hypoxia have a role in the planning of radiation therapy as these areas will have a higher innate resistance to therapy.
In people with lymphoma, a very early marker of response is reduced metabolic activity of cancer cells. It is now fairly common practice to screen patients using 18-FDG after a couple of weeks of treatment. Those that have had a response, the PET/CT has gone "cold," will remain on the standard treatment. Patients whose tumours are still showing activity on the scan will have an intensified protocol as it is known that their prognosis is worse though there is not good correlation of outcome in patients that have had a response.4 The physical size of the nodes between these two groups is very similar.
Another area where PET/CT is utilised is when patients are treated with newer agents such as tyrosine kinase inhibitors. In some of the diseases treated with this class of drugs there is often not a physical response, but rather a metabolic response. CT or other more traditional imaging will not detect the patients that are being helped by the treatments.
PET/CT has very limited availability for veterinary patients. If this can be changed it would have a role as a sensitive screening tool and monitoring treatment in a similar manner as has been utilised in people. This modality can also be used to show many other things as drugs, proteins and even cells can be labelled and tracked. It is possible to show that a drug targets the cancer and in what other tissues there is accumulation. If a patient is to be treated with a therapeutic antibody, PET/CT could be used to see if all the lesions will be targeted.
The advancements and sophistication of imaging modalities as well as the improvements in our standard modalities will help us in the management of veterinary oncology patients. Cost and access will be limiting factors, but these improving.
References
1. Turrel JM, McEntee MC, Burke BP, Page RL. Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990–2003). Journal of the American Veterinary Medical Association. 2006;229:542–548.
2. Nemanic S, London CA, Wisner ER. Comparison of thoracic radiographs and single breath-hold helical CT for detection of pulmonary nodules in dogs with metastatic neoplasia. Journal of Veterinary Internal Medicine. 2006;20:508–515.
3. Lawrence J, Vanderhoek M, Barbee D, Jeraj R, Tumas DB, Vail DM. Use of 3'-deoxy-3'-[18F] fluorothymidine PET/CT for evaluating response to cytotoxic chemotherapy in dogs with non-Hodgkin's lymphoma. Veterinary Radiology & Ultrasound. 2009;50:660–668.
4. Cashen AF, Dehdashti F, Luo J, Homb A, Siegel BA, Bartlett NL. 18F-FDG PET/CT for early response assessment in diffuse large B-cell lymphoma: poor predictive value of international harmonization project interpretation. Journal of Nuclear Medicine. 2011;52:386–392.