Vaccine Associated Sarcoma Diagnosis, Treatment and Prognosis
Dennis W. Macy DVM, MS
Recommendations for preventing or reducing the incidence of vaccine-associated tumors in cats are controversial. Recommendations include a change in vaccination site location, decreased use of polyvalent vaccines, use of nonadjuvanted vaccines, avoiding the use of aluminum based adjuvants, and not overvaccinating, among others.
The most important recommendation for prevention of vaccine-associated sarcomas would appear to be not to overvaccinate. Kass, et al. (1993) has clearly shown that the risk of vaccine-associated sarcomas increases with the number of vaccines administered. It is also clear from recently published articles by Scott, et al. (1997) that the duration of immunity of many of our feline products is longer than one year and an every three year program should be instituted for many vaccines for infectious agents of cats. Although the triennial vaccination program has been endorsed by the American Association of Feline Practitioners, it has not been warmly received by general practitioners in the United States. With respect to rabies vaccination, annual vaccination for rabies with a three-year rabies product should be discouraged. Most one year rabies vaccine used in the United States is really a three year rabies vaccine. Unfortunately, in the United States, a three-year rabies vaccine may be relabeled and sold as a one-year product. The indiscriminate use of FeLV vaccine should be stopped because epidemiologic data suggest it has the greatest association with the development of injection site sarcomas in cats. The recent article by Romatowski (1997) casts serious doubt whether vaccinating cats in single cat households has had any impact on the incidence of FeLV in that population. If FeLV vaccines are to be used at all, they should be reserved for high risk cats and given to the young prior to 12 weeks of age when the chance of developing persistent FeLV infection if exposed is 85%. Experimental studies have indicated that once cats are over 6 months of age, only 15% of exposed cats will develop persistent FeLV infections. Given the potential risk of sarcoma development (1-10/10,000), a veterinarian should really question the benefit of FeLV vaccination in individual cats. A veterinarian may be doing more harm than good in vaccinating against FeLV annually in the single cat household population. Fortunately, very few veterinarians in the United States now recommend FeLV vaccination for strictly indoor cats. The frequency of revaccination for FeLV should be based on duration of immunity studies, which are unfortunately still essentially absent for most all U.S. veterinary vaccines.
Vaccine site location recommendations have also recently been changed. The National Feline Vaccine-Associated Sarcoma Task Force recommends that no vaccine be given in the interscapular space, that rabies vaccine be administered subcutaneously in the distal right rear leg, that FeLV vaccine be administered subcutaneously in the distal left rear leg, and that all other vaccines be administered subcutaneously in the right shoulder. It appears from our research and reports by others that intramuscular and subcutaneous administration both result in local inflammation and tumor production. Subcutaneous sites are recommended for all vaccines since they will result in earlier detection of these growths if they occur.
The reasoning behind these vaccine site administration recommendations is not based so much on prevention but rather on earlier diagnosis and potentially a higher cure rate when treated surgically.
The issue of monovalent and polyvalent vaccines is still controversial. Kass (1993) found a significant positive trend in risk with an increasing number of vaccines. However, Hendrick, et al. found no association between vaccination-site and nonvaccination-site tumors in the number of vaccinations given simultaneously. Although ambiguity exists, it seems prudent to now recommend that vaccines be administered at different sites and not to use polyvalent vaccines. The current practice that all cats should receive all available feline vaccines annually is being seriously challenged by many veterinarians in the United States today, but still remains the way most practitioners vaccinate cats.
The use of vaccines containing aluminum-based adjuvants is controversial. The recommendation not to use multiple-dose vials for aluminum-adjuvanted vaccines appears less controversial. The fact that aluminum is in suspension and not solution makes it is difficult if not impossible to obtain an equal concentration of vaccine adjuvant and attached vaccine protein every time a dose is drawn up into a syringe. Recent work at our institution using atomic absorption spectrophotometry confirmed this hypothesis, thus only single-dose vaccine vials should be used if giving aluminum-adjuvanted vaccines. Because aluminum-adjuvanted products are the most consistent producers of vaccine-site inflammation, in my opinion, they should be avoided if possible! However, nonaluminum-based adjuvants have also been linked to vaccine-site tumors, and may be equally unsafe. More research is clearly needed to determine the real risk of aluminum adjuvanted-vaccine products in the induction of vaccine-site associated sarcomas.
It would appear that the problem of vaccine-site associated sarcomas will be with us for some time, and the question of what to do with postvaccination lumps is a practical one. Some rabies and FeLV vaccines produce postvaccinal lumps in 100% of the vaccinates but, fortunately, it has been observed that most resolve in two to three months. Very few vaccine-associated tumors occur sooner than three months following vaccination. Given these observations, we currently recommend that any vaccine site lumps present after three months from the time of vaccination be removed, but only after a biopsy. A biopsy will determine the magnitude of the surgery, i.e., lumpectomy versus radical surgery. We do not recommend excising the mass prior to biopsy. Attempts at simple excision of these tumors is seldom curative and ultimately leads to local recurrence with a more difficult second surgical attempt. Even attempts at aggressive wide surgical excision are often incomplete and result in a 30%-70% failure rate. There appears to be an advantage to refer these cases to a qualified surgeon before the second surgery is contemplated. After a second surgical intervention has been attempted, there appears to be no improvement in survival with referral to specialist surgeons. Rear leg amputation has a higher rate of cure than surgery in the interscapular space for vaccine-site associated sarcomas. Given the incomplete removal of these tumors even with aggressive surgery, radiation is often used before or after surgery. One study's interim survival analysis indicates a doubling of survival when radiation is included. Although the combination of surgery and radiation has increased tumor control rates in some studies, a significant number of cats still fail to respond to this combination. Several chemotherapy agents, including carboplatin, doxorubicin, cyclophosphamide, Cytoxan and vincristine, have been used in cats with vaccine-associated tumors. Most chemotherapeutic attempts result in partial responses, but some complete responses have been observed with these drugs. Immunomodulators have been used systemically or intralesionally, but response has been limited. Although the vast majority of vaccine-site associated sarcomas are only locally invasive, approximately 10%-20% will metastasize to the lungs or other sites.
The cost of the treatment for vaccine-site associated sarcomas can be significant and run into many thousands of dollars. The ethics of the veterinary profession and how we manage this problem are being watched by many, including the media. How we act on this issue is likely to have a profound effect on how our profession is perceived by the public for some time in the future.
Given the need for vaccination against rabies to prevent a lethal disease in cats and humans, there would appear to be a need to compensate owners for expenses associated with the treatment of sarcomas that develop after the administration of mandated vaccines like rabies. Perhaps it is time that the veterinary profession consider a vaccine injury act similar to the 1986 Childhood Vaccine Injury Act in use for humans injured by mandated vaccines such as diptheria-pertussis-tetanus (DPT) and measles-mumps-rubella (MMR) in the United States. More legislative support is also needed and required in truth in labeling of United States’ veterinary vaccines that have been associated with vaccine-site sarcoma development. Currently, the fact that a three-year rabies vaccine may be relabeled as a one-year product seems unacceptable. Equally unacceptable is the fact that FeLV vaccines are recommended by manufacturers to be given annually without any evidence of duration of immunity.
Unlike European vaccines, no minimum duration of immunity must be established prior to licensure for veterinary vaccines, so regardless if the duration of immunity is three months or a lifetime, U.S. vaccine manufacturer label recommendations are “annual revaccination”. A critical look at duration of immunity using our understanding of immunity derived from previous natural infection, the prevalence of disease in cats previously vaccinated for the disease, as well as serologic data when appropriate, should help the profession establish more realistic booster intervals and a reduction in the number of vaccines administered and, hopefully, a reduction in vaccine-associated sarcoma development.