Dealing With Feline Vaccine-Associated Sarcomas

Bernard Séguin, DVM, MS, Dip ACVS

 

There is convincing epidemiologic evidence that show a strong association between the administration of inactivated feline vaccines (feline leukemia and rabies) and subsequent soft tissue sarcoma development at the vaccine injection site. Other vaccines such as panleukopenia and feline rhinotracheitis have also been associated with the development of sarcomas. The prevalence of soft tissue sarcoma development has been reported between 1/1000 to 1/10,000 vaccines administered. Feline vaccine-associated sarcomas are very frustrating to treat because of their aggressive nature, mostly with respect to local invasiveness, and our inability to achieve a cure in most cases.

Clients should be informed of the risks of vaccine-associated sarcomas and the occurrence of local vaccine reactions. Because early detection and intervention, more than likely, plays a very important role in the final outcome, the client should be showed how to monitor and evaluate the vaccination site and ask for veterinary assistance if any of the three following scenarios occur: 1) a lump is still present three months post-vaccination, 2) the lump is increasing in size one month post-vaccination, or 3) the lump is larger than two centimeters in diameter. The client should not hesitate to seek veterinary assistance if there is any doubt. After confirmation of one of those three scenarios by the veterinarian, a biopsy should be performed to find out if it is a reactive mass or a sarcoma. If the mass is a vaccine reaction then marginal excision should be performed. The impact of excision of a vaccine reaction on subsequent tumor development at the site has not been elucidated. If the mass is a sarcoma, proper treatment planning becomes imperative.

 Treatment planning: Once a diagnosis of sarcoma has been confirmed by biopsy or is highly suspected at a vaccination site, staging the patient is an important part of the planning. A complete blood count, chemistry panel, urinalysis along with FeLV and FIV tests will determine the overall health status. Although no association is apparent between viral status (FeLV, FIV) and tumor development, the course of the disease may be altered because of compromise of the immune system.

 Thoracic radiographs should be performed to look for evidence of matastasis, which occurs in 10 to 24% of the cases. Regional lymph nodes should be evaluated through palpation, radiographs, or ultrasonography. Advanced imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) are extremely helpful in planning a surgical plan and potentially decide to perform radiation therapy first. In a study to evaluate the usefulness of CT imaging of vaccine-associated sarcomas, the CT study revealed the tumor to be, on average, twice as large as determined by physical examination and caliper measurement. A biopsy should always be performed to confirm the diagnosis.

 Surgery: Attempts at simple excision (i.e. debulking or marginal excision) is rarely curative and ultimately leads to local recurrence with a more difficult second surgery. Even attempts at aggressive wide surgical excision are often incomplete and result in a 30% to 70% failure rate. Rear leg amputation has a higher rate of cure than surgery in the interscapular space but in some instances, amputation, hemipelvectomy, or both will still not provide a cure. Even when a histopathology report indicates no evidence of tumor cells at the surgical margins, there may be a 50% local recurrence rate. However, cats with aggressive excision at first attempt have longer tumor-free intervals than marginal excision (325 days versus 79 days) and cats with complete excision have a longer tumor-free interval (>16 months versus 4 months) and survival time (>16 months versus 9 months) than those with incomplete excision.

 Therefore aggressive surgical excision should be attempted. This means 3cm margins laterally and one fascial plane deep to the tumor. If the tumor involves or comes so close as to not be separated by a fascial plane from the scapula, a spinous process, or pelvis, then a scapulectomy, spinous process resection, or hemipelvectomy needs to be performed en bloc with the tumor excision.

 Radiation therapy: Given the incomplete removal of these tumors and the relatively high recurrence rate in spite of aggressive surgery, radiation is often used before or after surgery. Radiation therapy alone is not recommended to treat vaccine-associated sarcomas if the intent is cure. Irradiation of bulky disease is palliative in that the goal is to make the patient more comfortable (the tumor may or may not decrease in size) but longevity is not expected to improve.

 The combination of surgery and radiation therapy seems to have increased the tumor control rate. Irradiation can be performed in the preoperative or postoperative settings.

In one study where cats received 48 Gy in 16 daily 3 Gy fractions, the median disease-free interval was 398 days and the median survival was 600 days. In this study the irradiation was delivered in the preoperative setting and status of the surgical margins was a significant prognostic factor for treatment success: median disease-free interval was 112 days for incomplete surgical margins versus 700 days for complete margins. It appears that complete surgical excision is of great importance and therefore aggressive surgery should be performed irrespective of the addition of adjuvant radiotherapy. However, a study presented at the last Veterinary Cancer Society Annual Conference (20th Annual Conference, Pacific Grove, 2000) did not support this principle. There was no difference in local recurrence between conservative excision and wide excision when combined with irradiation but there were few cats in this study and the power of the test was therefore very low. Until more evidence becomes available to the contrary, aggressive excision should remain the standard of care. On the other hand, there is some evidence to suggest that a very aggressive resection, meaning 5 cm margins laterally and two muscle planes deep, could be sufficient as the sole treatment in a majority of cats with injection-site sarcomas, thereby avoiding radiation therapy.

   Chemotherapy alone should not be considered for definitive therapy. However, in the adjuvant or neoadjuvant setting, chemotherapy may play an important role in the multimodality approach to treatment. The use of various chemotherapy protocols has resulted in some partial and less frequent complete responses. Therefore chemotherapy in the preoperative setting may reduce tumor size thereby facilitating surgical resection or chemotherapy can also be used as a radiation sensitizer. Agents that have been used include doxorubicin, cyclophosphamide, carboplatin, mitoxantrone, and vincristine. Different studies come to different conclusions regarding the benefit of using chemotherapy but at this point in time there seems to be more scientific evidence to supports its use. Although the metastatic rate is relatively low (10 to 24%), systemic chemotherapy may play a role in the delay or prevention of the development of metastatic disease and needs to be further investigated 

 In spite of the fact that significant progress has been made in the treatment of feline vaccine-associated sarcomas and that the best results seem to be attained with a multimodality approach, meaning combination aggressive surgery, radiation therapy, and chemotherapy, many questions remain unanswered and too many patients still have a treatment failure. Because feline patients present to the veterinarian with tumors of different sizes and at different locations, the best treatment in each instance remains unknown. For example, it is not known whether aggressive surgery alone is sufficient for long-term control in cats with relatively small (<3 cm), discrete, and noninfiltrative tumors that have not previously been resected. Because factors that can predict the biological and clinical behavior have not been fully identified yet, aggressive multimodality therapy for all cats with vaccine-associated sarcomas appears necessary at this time. Treatment recommendations will certainly become more precise and refined for each individual cat as more is learned about this terrible disease.

 Recommendations for vaccination:  

 Vaccine site location recommendations are as follows:

 The reasoning behind some of these recommendations is not based so much on prevention but rather on earlier diagnosis (subcutaneous versus intramuscular injection) and potentially higher cure rate when treated surgically (distal limb versus interscapular space).    


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