14 The lame cancer patient
The identification of an animal being lame due to a neoplastic disease usually causes owners significant distress as they face the possibility of considering amputation of the affected limb, whilst for the veterinary surgeon some careful diagnostic evaluation will be required for the case to ensure the tumour found is primary as opposed to being secondary, to ensure that there are no detectable secondary tumours present and also to consider all of the treatment options available. It is also important to remember that lameness may indicate spinal or neurological disease, so thorough clinical evaluation is essential to be sure that the clinical extent of the condition has been fully established.
The dog received chemotherapy in the form of alternating carboplatin and doxorubicin given once every 3 weeks for a total of six treatments. The dog was alive and well with no evidence of pulmonary metastasis at 12 months after the surgery.
Osteosarcoma (OSA) is a highly malignant mesenchymal tumour originating in primitive bone cells that has been reported to account for up to 85% of all skeletal malignancies in the dog. It is a disease seen most frequently in large/giant-breed dogs in particular. There is a positive correlation with the height of the animal and the development of the disease. It is not surprising therefore to see that the breeds that develop the disease most frequently are Saint Bernards, great Danes, dobermans, Irish setters, rottweilers, German shepherd dogs and golden retrievers. The disease is reported in small-breed dogs but with very low frequency (no more than 5% of all cases). Most cases involving the appendicular skeleton develop in middle- to older-aged dogs with an average age of 7 years (although it can certainly develop in quite young dogs), but OSA of the rib is most commonly seen in younger dogs at approximately 5 years of age. There may be a slight gender predilection for males developing the disease, but the data in some studies suggest there is no gender bias in OSA, so this question is currently unresolved. The tumour, as in this case, most commonly develops in the metaphyseal region of the long bones and the front limbs appear to be affected more frequently than the hind legs.
The tumour has significant local effects, with new bone development and osteolysis often occurring concurrently. This leads to distortion of the periosteum, microfracture formation and often quite marked pain. It is not possible to definitively diagnose an OSA on radiographs alone (although suspicion can be very high), but it is this mixed pathology that generates the ‘classic’ peripheral pallisading new bone appearance admixed with (sometimes patchy) cortical lysis and obvious soft tissue swelling on radiographic examinations. In addition to being locally destructive, OSA also usually exhibits aggressive metastatic behaviour, with the lungs being the primary target location for the development of secondary disease. This is why it is mandatory to obtain good-quality left and right lateral inflated thoracic radiographs as a minimum diagnostic imaging evaluation prior to undertaking any surgical treatments. Other potential metastasis sites include other bones or any soft tissues.
Any dog therefore presenting with a non-resolving lameness that has an accompanying soft-tissue swelling should always undergo a radiographic evaluation, with OSA as a major concern if the dog is a large or giant breed. However, it is very important to remember to examine the whole dog, as it is possible that the tumour could be a secondary lesion. Bony metastases often originate from a carcinoma, so the anal sacs need to be evaluated with a digital rectal examination as does the prostate, along with a careful palpation of the mammary glands, as part of a detailed physical examination to try to establish whether there is disease elsewhere or not.
If the presentation of the patient is potentially consistent with a primary bone tumour, a decision has to be made whether or not to biopsy the lesion. Although in most scenarios it is vitally important to obtain a definitive diagnosis before contemplating a treatment such as amputation, if the dog, as in the case reported here, is obviously in substantial pain and the opinion of the attending clinician is that amputation may actually be the best form of analgesia the dog can receive, surgical removal of the problem with postoperative histology may be acceptable. If amputation is a treatment option that is declined by the owners, then it is essential to obtain samples for biopsy. Usually the simplest and safest way to obtain a bone biopsy sample is to use a Jamshidi needle device. These needles can be quite large but it is very important to get as much tissue as it is safely possible to do, as the histological appearance can vary within individual biopsy samples and a superficial or small biopsy may generate a misleading result. A simple closed biopsy procedure under a brief general anaesthesia is usually more than adequate, but the owners must be warned regarding the risk of pathological fracture at the biopsy site due to the pre-existing bone weakness and distortion.
Once the diagnosis has been confirmed, the first-line treatment is to surgically amputate the affected limb and then to give adjunctive chemotherapy, as it is likely that microscopic metastases will be present in virtually all cases. Limb amputation is the most common surgical treatment for canine and feline appendicular OSA. Most animals with OSA will have naturally shifted the majority of their weight bearing onto three legs for some time prior to the surgery so tend to function well after the procedure. There are in fact few contraindications for limb amputation and even dogs with mild to moderate degenerative joint disease in other joints can do extremely well, as do the giant breeds of dogs. However, although the majority of owners are pleased with the outcome the decision to amputate must be discussed carefully and owners’ sensitivities towards the operation taken into account.
For forelimbs it is easier to perform a complete forequarter amputation (involving removal of the scapula) rather than shoulder disarticulation. The cosmetic result is very good using this technique as there is no muscle atrophy that occurs over the scapula associated with the latter technique. It also allows for complete removal of local disease. For the hind limbs a coxofemoral amputation is generally recommended for complete disease excision, however, with distal tibial tumours then a mid-shaft femoral amputation is also acceptable, with some surgeons preferring this as it affords some protection to male genitalia. For any amputation, electrocautery is a useful means of controlling haemorrhage from smaller vessels. However, it should not be used excessively and ligation techniques are necessary for larger arteries and veins. If possible muscles should be separated at their origins or insertions. Arteries and veins are ligated separately (and in this order) with major vessels double ligated before division. Nerves are sharply divided after infiltration with local anaesthetic. When closing the wound the surgeon should focus on eliminating dead space and controlling haemorrhage to help avoid complications such as wound seroma and dehiscence.
These patients often display the ‘wind-up’ phenomenon seen in patients with long-term pain, so they require excellent analgesia in their premedication, through surgery and in the immediate 24–48 hours postoperatively. They require regular reassessment to establish their levels of pain control.
Once the limb has been amputated and the dog has recovered, attention must turn to adjunctive chemotherapy. Without follow-up treatment, secondary disease often develops very rapidly (within as short a time as 3 months) and this is thought to be due to the fact that microscopic metastatic disease is likely to be present in most cases by the time they present. Many different drug regimens have been evaluated and it is clear that the platinum drugs definitely generate substantial improvements in life expectancy and outcome. Doxorubicin also shows activity against OSA but with less efficacy as a single agent when compared to the platinum drugs, so currently the authors use an alternating carboplatin/doxorubicin protocol where the drugs are given at 21-day intervals for a total of six treatments. The authors generally use carboplatin in preference to cisplatin due to its relative ease of handling, lower side effect risk and the relatively fewer health and safety concerns regarding carboplatin. This protocol has been reported to generate median survival times of 321 days with a 1-year survival rate of 48% and a 2-year survival rate of 18%. However, many other treatment combinations have been reported in which the drugs used (cisplatin, carboplatin, lobaplatin, doxorubicin), the doses used and interdose intervals are all varied and a general observation would be that most protocols generate median survival times of approximately 1 year and have 1-year survival rates of between 30 and 50%. Two-year survival rates with this approach are low.
To try to improve these figures, alternative treatment possibilities have been reported. ‘Limb-sparing’ surgery has been extensively investigated and performed at the Colorado State University Animal Cancer Center (CSU ACC) in the USA and also at several other centres around the world and this has proved to be a successful technique in most cases but the procedure requires an experienced and dedicated clinical team and very dedicated owners. It is a technique that can be performed for radial, ulnar, tibial or fibular OSA and in essence the procedure involves surgically excising the tumour and then replacing the bone deficit usually with a cortical allograft, although the use of metal endo-prostheses has been described, as has pasteurizing the excised bone tumour section before re-implanting it. A review of over 200 cases at CSU from the 1990s reported that the 1-year survival rates were 60% with the 1-year local disease-free rate being over 75%. Currently this is not a commonplace procedure in the UK but with more surgeons visiting and training in the USA, it may well become a more routine procedure in this country.
If surgery is not a viable option for any reason, then external beam radiotherapy can help to generate some significant analgesia for OSA patients for up to approximately 3 months when given as a two-fraction treatment, usually administering up to 10 Gy per fraction. The concern regarding radiotherapy is that it may increase bone weakness at the tumour site and therefore lead to an increased risk of the dog developing a pathological fracture, especially if the analgesic action is sufficient for the dog to use the leg almost normally. Analgesia can be augmented with the NSAID meloxicam, as not only is it a highly effective non-steroidal anti-inflammatory analgesic, it is now under investigation as an antineoplastic agent itself. In addition, the author has had some experience of using oral and injectable bisphosphonates in OSA patients. Bisphosphonates are osteoclast inhibitors and it is thought that osteoclast activity is one of the major causes of pain in bone cancer, so antagonizing these cells may help OSA patients (Figs 14.2, 14.3).
Figures 14.2, 14.3 Lateral radiograph and T1 plus contrast sagittal MRI scan of the femur of a Gordon setter with a large osteosarcoma in the mid-section of the bone with a large resultant local soft-tissue involvement. Note the significant extension of the tumour through the medullary cavity that is visible on the MRI but there is no evidence of it on the radiograph. Amputation was declined, so the dog was treated with two cycles of external beam radiotherapy, single-agent carboplatin chemotherapy, oral meloxicam and the bisphosphonate ‘alendronate’. The dog became completely sound again and remained non-lame for 6 months.
Courtesy of Dr Hervé Brissot, Dick White Referrals